Identification

Name
Ibrutinib
Accession Number
DB09053
Type
Small Molecule
Groups
Approved
Description

Ibrutinib is a small molecule that acts as an irreversible potent inhibitor of Burton's tyrosine kinase. It is designated as a targeted covalent drug and it presents a very promising activity in B cell malignancies.[4] Ibrutinib was developed by Pharmacyclics Inc and in November 2013 was FDA-approved for the treatment of mantle cell lymphoma. Later, in February 2014, ibrutinib was approved for the treatment of chronic lymphocytic leukemia and it is also indicated for the treatment of patients with Waldenström's Macroglobulinemia.[13] Ibrutinib has also been approved by the EMA for the treatment of chronic lymphocytic leukemia and mantle cell lymphoma.[4] Ibrutinib was approved for use in chronic graft versus host disease in August 2017 [12].

Structure
Thumb
Synonyms
  • 1-[(3R)-3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one
External IDs
CRA-032765 / PC-32765 / PCI 32765 / PCI-32765 / PCI-32765-00
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ImbruvicaCapsule70 mg/1OralPharmacyclics LLC2017-12-20Not applicableUs
ImbruvicaCapsule140 mgOralJanssen Pharmaceuticals2014-11-19Not applicableCanada
ImbruvicaTablet, film coated560 mg/1OralPharmacyclics LLC2018-02-16Not applicableUs
ImbruvicaTablet, film coated140 mg/1OralPharmacyclics LLC2018-02-16Not applicableUs
ImbruvicaCapsule140 mgOralJanssen Cilag International Nv2014-10-21Not applicableEu
ImbruvicaTablet, film coated420 mg/1OralPharmacyclics LLC2018-02-16Not applicableUs
ImbruvicaCapsule140 mg/1OralPharmacyclics LLC2013-11-13Not applicableUs
ImbruvicaCapsule140 mgOralJanssen Cilag International Nv2014-10-21Not applicableEu
ImbruvicaTablet, film coated280 mg/1OralPharmacyclics LLC2018-02-16Not applicableUs
Categories
UNII
1X70OSD4VX
CAS number
936563-96-1
Weight
Average: 440.507
Monoisotopic: 440.196074037
Chemical Formula
C25H24N6O2
InChI Key
XYFPWWZEPKGCCK-GOSISDBHSA-N
InChI
InChI=1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1
IUPAC Name
1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one
SMILES
NC1=NC=NC2=C1C(=NN2[C@@H]1CCCN(C1)C(=O)C=C)C1=CC=C(OC2=CC=CC=C2)C=C1

Pharmacology

Indication

Ibrutinib acquired an accelerated approval for the treatment of mantle cell lymphoma who have received at least one prior therapy.[Label] Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma that develops in the outer edge of a lymph node. MCL is usually diagnosed at late stages and it is easily spread into bone marrow, spleen, liver and gastrointestinal tract.[14]

Ibrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL) who have at least one prior therapy.[Label] CLL is a type of cancer caused by an overproduction of lymphocytes by the bone marrow. Some of the symptoms include swollen lymph nodes and tiredness.[15]

Ibrutinib is indicated for the treatment of chronic lymphocytic leukemia (CLL) with 17p deletion.[Label] CLL with 17p is a type of leukemia in which a deletion in 17p disrupts the tumor suppressor p53 by deleting one allele of the TP53 gene. The remaining allele is mainly inactivated and thus, this type of leukemia is unresponsive to p53-dependent treatments.[5]

Ibrutinib is indicated for the treatment of patients with Waldenstrom's Macroglobulinemia (WM).[Label] WM, also called lymphoplasmacytic lymphoma, is a type of non-Hodgkin lymphoma in which the cancer cells make large amounts of macroglobulin. The macroglobulin is a monoclonal protein that corresponds to the type of IgM antibodies and the unrestricted formation of this protein causes typical symptoms such as excessive bleeding and effects in vision and nervous system.[16]

Associated Conditions
Pharmacodynamics

In vitro studies have shown an induction of CLL cell apoptosis even in presence of prosurvival factors. It has also been reported an inhibition of CLL cell survival and proliferation as well as an impaired in cell migration and a reduction in the secretion of chemokines such as CCL3 and CCL4. The latter effect has been shown to produce regression in xenograft mouse models.[6]

Clinical studies for relapsed/refractory CLL in phase I and II showed an approximate 71% of overall response rate.[7, 8]. In the case of relapsed/refractory mantle cell lymphoma, approximately 70% of the tested patients presented a partial or complete response.[7, 9]. In clinical trials for relapsed/refractory diffuse large B-cell lymphoma, a partial response was found in between 15-20% of the patients studied; while for patients with relapsed/refractory Waldenstrom's macroglobulinemia, a partial response was observed in over 75% of the patients tested. Finally, for patients with relapsed/refractory follicular lymphoma, a partial to complete response was obtained in approximately 54% of the patients.[7]

Mechanism of action

Ibrutinib is an inhibitor of Bruton’s tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue in the active site of BTK (Cys481), leading to its inhibition. The inhibition of BTK plays a role in the B-cell receptor signaling and thus, the presence of ibrutinib prevents the phosphorylation of downstream substrates such as PLC-γ.[6]

TargetActionsOrganism
ATyrosine-protein kinase BTK
inhibitor
Human
Absorption

Ibrutinib is rapidly absorbed after oral administration and it presents a Cmax, tmax and AUC of approximately 35 ng/ml, 1-2 hour and 953 mg.h/ml respectively.[11]

Volume of distribution

The volume of distribution at steady-state of ibrutinib is in approximately 10,000 L.[11]

Protein binding

Irreversible plasma protein binding increases gradually over time and reaches 25% of the administered dose 8 hours after initial administration. From the plasma proteins, ibrutinib has been shown to be mainly bound to albumin and to bind to α1 AGP.[3] The irreversible protein binding of ibrutinib to plasma proteins can account for 97.3% of the administered dose.[11]

Metabolism

Three metabolic pathways have been identified according to the possible metabolites. These pathways are the hydroxylation of the phenyl group (M35), the opening of the piperidine with a reduction of the primary alcohol (M34) and the oxidation to a carboxylic acid and epoxidation of the ethylene followed by a hydrolysis to the formation of dihydrodiol (PCI-45227). The latter metabolite presents also 15 times lower inhibitory activity against BTK. The metabolism of ibrutinib is mainly performed by CYP3A5 and CYP3A4. and in a minor extent it is seen to be performed by CYP2D6.[3]

Route of elimination

The cumulative excretion of ibrutinib in urine is of about 7.8% of the administered dose and most of this excretion is found during the first 24 hours after administration. In feces, the cumulative excretion accounts for 80% of the administered dose and the excretion occurs within 48 hours of the initial administration. The total excretion of ibrutinib during the first 168 hours after initial administration accounts for 88.5% of the administered dose.[3]

Half life

The elimination half-life of ibrutinib is of approximately 4-6 hours.[11]

Clearance

In patients with normal renal function, the clearance rate is in the range of 112-159 ml/min.[3]

Toxicity

Ibrutinib was not showed to present a mutagenic potential in bacterial assays, nor clastogenic in chromosome aberration assays in mammalian cells or in bone marrow micronucleus assays in mice. Carcinogenicity or effects on fertility have not been determined.[Label]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Abciximab.
AbirateroneThe serum concentration of Ibrutinib can be increased when it is combined with Abiraterone.
AcenocoumarolThe risk or severity of bleeding and hemorrhage can be increased when Ibrutinib is combined with Acenocoumarol.
AcetazolamideThe serum concentration of Ibrutinib can be increased when it is combined with Acetazolamide.
Acetyl sulfisoxazoleThe serum concentration of Ibrutinib can be increased when it is combined with Acetyl sulfisoxazole.
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Ibrutinib.
AcetyldigoxinAcetyldigoxin may decrease the cardiotoxic activities of Ibrutinib.
Acetylsalicylic acidThe risk or severity of adverse effects can be increased when Ibrutinib is combined with Acetylsalicylic acid.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Ibrutinib.
AlbendazoleThe metabolism of Ibrutinib can be decreased when combined with Albendazole.
Food Interactions
  • Administration with food increases ibrutinib exposure approximately 2-fold compared with administration after overnight fasting.

References

General References
  1. Bagcchi S: Ibrutinib in pretreated Waldenstrom's macroglobulinaemia. Lancet Oncol. 2015 May;16(5):e204. doi: 10.1016/S1470-2045(15)70185-3. Epub 2015 Apr 16. [PubMed:25892147]
  2. Kim ES, Dhillon S: Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Drugs. 2015 May;75(7):769-76. doi: 10.1007/s40265-015-0380-3. [PubMed:25802231]
  3. Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, Cuyckens F, Skee D, Murphy J, Sukbuntherng J, Mannens G: Absorption, metabolism, and excretion of oral (1)(4)C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97. doi: 10.1124/dmd.114.060061. Epub 2014 Dec 8. [PubMed:25488930]
  4. Berglof A, Hamasy A, Meinke S, Palma M, Krstic A, Mansson R, Kimby E, Osterborg A, Smith CI: Targets for Ibrutinib Beyond B Cell Malignancies. Scand J Immunol. 2015 Sep;82(3):208-17. doi: 10.1111/sji.12333. [PubMed:26111359]
  5. Sellner L, Denzinger S, Dietrich S, Glimm H, Merkel O, Dreger P, Zenz T: What do we do with chronic lymphocytic leukemia with 17p deletion? Curr Hematol Malig Rep. 2013 Mar;8(1):81-90. doi: 10.1007/s11899-012-0143-0. [PubMed:23188619]
  6. Davids MS, Brown JR: Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase. Future Oncol. 2014 May;10(6):957-67. doi: 10.2217/fon.14.51. [PubMed:24941982]
  7. Advani RH, Buggy JJ, Sharman JP, Smith SM, Boyd TE, Grant B, Kolibaba KS, Furman RR, Rodriguez S, Chang BY, Sukbuntherng J, Izumi R, Hamdy A, Hedrick E, Fowler NH: Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies. J Clin Oncol. 2013 Jan 1;31(1):88-94. doi: 10.1200/JCO.2012.42.7906. Epub 2012 Oct 8. [PubMed:23045577]
  8. Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, Grant B, Sharman JP, Coleman M, Wierda WG, Jones JA, Zhao W, Heerema NA, Johnson AJ, Sukbuntherng J, Chang BY, Clow F, Hedrick E, Buggy JJ, James DF, O'Brien S: Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013 Jul 4;369(1):32-42. doi: 10.1056/NEJMoa1215637. Epub 2013 Jun 19. [PubMed:23782158]
  9. Wang ML, Rule S, Martin P, Goy A, Auer R, Kahl BS, Jurczak W, Advani RH, Romaguera JE, Williams ME, Barrientos JC, Chmielowska E, Radford J, Stilgenbauer S, Dreyling M, Jedrzejczak WW, Johnson P, Spurgeon SE, Li L, Zhang L, Newberry K, Ou Z, Cheng N, Fang B, McGreivy J, Clow F, Buggy JJ, Chang BY, Beaupre DM, Kunkel LA, Blum KA: Targeting BTK with ibrutinib in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2013 Aug 8;369(6):507-16. doi: 10.1056/NEJMoa1306220. Epub 2013 Jun 19. [PubMed:23782157]
  10. Authors unspecified: Ibrutinib. Aust Prescr. 2015 Oct;38(5):178-80. Epub 2015 Jun 15. [PubMed:26648658]
  11. Bronson J., Black A., Dhar M., Ellsworth B. and Merritt R. (2014). Annual reports in medicinal chemistry. Elsevier.
  12. FDA: Ibrutinib cGVHD approval [Link]
  13. FDA approved drugs [Link]
  14. Canadian cancer society [Link]
  15. National Cancer Institute [Link]
  16. American Cancer Society [Link]
External Links
KEGG Drug
D10223
PubChem Compound
24821094
PubChem Substance
310264995
ChemSpider
26637187
BindingDB
50357312
ChEBI
76612
ChEMBL
CHEMBL1873475
PharmGKB
PA166121346
HET
1E8
Drugs.com
Drugs.com Drug Page
Wikipedia
Ibrutinib
ATC Codes
L01XE27 — Ibrutinib
AHFS Codes
  • 10:00.00 — Antineoplastic Agents
PDB Entries
4ifg / 4rz7 / 5p9i / 5yu9
FDA label
Download (579 KB)
MSDS
Download (24.9 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Not Yet RecruitingTreatmentMalignant Neoplasms Stated as Primary Lymphoid Haematopoietic / Mantle Cell Lymphoma (MCL)1
0RecruitingTreatmentFollicular Lymphoma (FL) / Follicular Lymphoma Grade IIIa / Follicular Lymphoma, Grade 1 / Follicular Lymphoma, Grade 21
0RecruitingTreatmentMalignant Lymphomas / Mantle Cell Lymphoma (MCL)1
1Active Not RecruitingOtherLeukemia, Lymphocytic, Chronic, B-Cell1
1Active Not RecruitingTreatmentAnn Arbor Stage II Grade 1 Contiguous Follicular Lymphoma / Ann Arbor Stage II Grade 1 Non-Contiguous Follicular Lymphoma / Ann Arbor Stage II Grade 2 Contiguous Follicular Lymphoma / Ann Arbor Stage II Grade 2 Non-Contiguous Follicular Lymphoma / Ann Arbor Stage II Grade 3 Contiguous Follicular Lymphoma / Ann Arbor Stage II Grade 3 Non-Contiguous Follicular Lymphoma / Ann Arbor Stage III Grade 1 Follicular Lymphoma / Ann Arbor Stage III Grade 2 Follicular Lymphoma / Ann Arbor Stage III Grade 3 Follicular Lymphoma / Ann Arbor Stage IV Grade 1 Follicular Lymphoma / Ann Arbor Stage IV Grade 2 Follicular Lymphoma / Ann Arbor Stage IV Grade 3 Follicular Lymphoma / CD20 Positive / Stage II Grade 1 Contiguous Follicular Lymphoma / Stage II Grade 1 Non-Contiguous Follicular Lymphoma / Stage II Grade 2 Contiguous Follicular Lymphoma / Stage II Grade 2 Non-Contiguous Follicular Lymphoma / Stage II Grade 3 Contiguous Follicular Lymphoma / Stage II Grade 3 Non-Contiguous Follicular Lymphoma / Stage III Grade 1 Follicular Lymphoma / Stage III Grade 2 Follicular Lymphoma / Stage III Grade 3 Follicular Lymphoma / Stage IV Grade 1 Follicular Lymphoma / Stage IV Grade 2 Follicular Lymphoma / Stage IV Grade 3 Follicular Lymphoma1
1Active Not RecruitingTreatmentAnn Arbor Stage III Small Lymphocytic Lymphoma / Ann Arbor Stage IV Small Lymphocytic Lymphoma / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma / Stage III Chronic Lymphocytic Leukemia / Stage III Small Lymphocytic Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma1
1Active Not RecruitingTreatmentB-Cell Prolymphocytic Leukemia / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Leukemia, Prolymphocytic / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma1
1Active Not RecruitingTreatmentCCND1 Positive / Recurrent Mantle Cell Lymphoma / T(11;14)1
1Active Not RecruitingTreatmentCancers1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Non-Hodgkin's Lymphoma (NHL)1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma1
1Active Not RecruitingTreatmentChronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma / Mantle Cell Lymphoma (MCL)1
1Active Not RecruitingTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Splenic Marginal Zone Lymphoma / Waldenström's Macroglobulinemia (WM)1
1Active Not RecruitingTreatmentExtranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue / Nodal Marginal Zone Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Lymphoplasmacytic Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Lymphoplasmacytic Lymphoma / Refractory Mantle Cell Lymphoma / Splenic Marginal Zone Lymphoma / Waldenström's Macroglobulinemia (WM)1
1Active Not RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphomas / Mantle Cell Lymphoma (MCL)1
1Active Not RecruitingTreatmentLeukemia, Lymphocytic1
1Active Not RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
1Active Not RecruitingTreatmentMalignancies, Hematologic1
1Active Not RecruitingTreatmentChronic, recurrent Lymphoid Leukemia1
1CompletedNot AvailableHealthy Volunteers1
1CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia1
1CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (SLL)1
1CompletedTreatmentCD20 Positive / Recurrent Diffuse Large B-Cell Lymphoma / Refractory Diffuse Large B Cell Lymphoma1
1CompletedTreatmentHealthy Participants2
1CompletedTreatmentHealthy Volunteers6
1CompletedTreatmentHepatic Impairment1
1CompletedTreatmentLeukemia, B-Cell / Lymphoma, B-Cell1
1CompletedTreatmentRecurrent Mature B-cell Neoplasms1
1RecruitingTreatmentAnn Arbor Stage II Diffuse Large B-Cell Lymphoma / Ann Arbor Stage III Diffuse Large B-Cell Lymphoma / Ann Arbor Stage IV Diffuse Large B-Cell Lymphoma / CD20 Negative / CD20 Positive / HIV Positivity / Human Immunodeficiency Virus Positive / Lymphoma, AIDS Related / Stage II Diffuse Large B-Cell Lymphoma / Stage III Diffuse Large B-Cell Lymphoma / Stage IV Diffuse Large B-Cell Lymphoma1
1RecruitingTreatmentB-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classical Hodgkin Lymphoma / Grade 1 Follicular Lymphoma / Grade 2 Follicular Lymphoma / Grade 3a Follicular Lymphoma / Mediastinal Lymphoma / Recurrent B-Cell Non-Hodgkin Lymphoma / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Recurrent Lymphoplasmacytic Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Waldenstrom Macroglobulinemia / Refractory B-Cell Non-Hodgkin Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Lymphoplasmacytic Lymphoma / Refractory Mantle Cell Lymphoma1
1RecruitingTreatmentB-Cell Prolymphocytic Leukemia / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Follicular Lymphoma / Recurrent Lymphoplasmacytic Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Lymphoplasmacytic Lymphoma / Refractory Mantle Cell Lymphoma / Refractory Marginal Zone Lymphoma / Refractory Non-Hodgkin's lymphoma / Refractory Small Lymphocytic Lymphoma / Richter's Syndrome1
1RecruitingTreatmentBurkitt's Lymphoma / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphomas / Non-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentCCND1 Positive / CD20 Positive / Recurrent Diffuse Large B-Cell Lymphoma / Recurrent Mantle Cell Lymphoma / Refractory Diffuse Large B Cell Lymphoma / Refractory Mantle Cell Lymphoma / Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)5
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Peripheral T-Cell Lymphoma (PTCL)1
1RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
1RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Leukemia, Prolymphocytic / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Small Lymphocytic Lymphoma1
1RecruitingTreatmentChronic Myelomonocytic Leukemia / De Novo Myelodysplastic Syndrome / Previously Treated Myelodysplastic Syndromes / Refractory Anemia With Excess Blasts in Transformation / Secondary Myelodysplastic Syndromes1
1RecruitingTreatmentGlioblastomas1
1RecruitingTreatmentLymphoma, B-Cell2
1RecruitingTreatmentMantle Cell Lymphoma (MCL)1
1RecruitingTreatmentMantle Cell Lymphoma (MCL) / Recurrent Lymphoma, Mantle-Cell1
1RecruitingTreatmentMetastatic Malignant Solid Neoplasm1
1RecruitingTreatmentMyelodysplastic Syndrome / Previously Treated Myelodysplastic Syndromes / Refractory High Risk Myelodysplastic Syndrome / Secondary Myelodysplastic Syndromes / Therapy-Related Myelodysplastic Syndrome1
1RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
1RecruitingTreatmentRefractory Diffuse Large B Cell Lymphoma / Relapsed, Diffuse Large B-cell Lymphoma1
1RecruitingTreatmentRelapsed and Refractory T-cell Lymphoma / T-Cell Lymphomas1
1SuspendedTreatmentPrimary Central Nervious System Lymphoma1
1TerminatedTreatmentAdult B Acute Lymphoblastic Leukemia / Chronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leukemia (CLL) - Refractory / Cutaneous B-Cell Non-Hodgkin Lymphoma / Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue / Human Immunodeficiency Virus (HIV) Infections / Intraocular Lymphoma / Multicentric Angiofollicular Lymphoid Hyperplasia / Nodal Marginal Zone Lymphoma / Recurrent Adult Acute Lymphoblastic Leukemia / Recurrent Adult Burkitt Lymphoma / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Adult Grade III Lymphomatoid Granulomatosis / Recurrent Adult Immunoblastic Lymphoma / Recurrent Adult Lymphoblastic Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Refractory Hairy Cell Leukemia / Refractory Plasma Cell Myeloma / Small Intestinal Lymphoma / Splenic Marginal Zone Lymphoma / Testicular Lymphoma / Waldenström's Macroglobulinemia (WM)1
1TerminatedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
1TerminatedTreatmentRecurrent Adult Acute Myeloid Leukemia1
1WithdrawnTreatmentAcute Lymphoblastic Leukaemias (ALL)1
1WithdrawnTreatmentCancers1
1WithdrawnTreatmentCore: Relapsed or Refractory Diffuse Large B-Cell Lymphoma / Module 1: Non-GCB Diffuse Large B-Cell Lymphoma1
1WithdrawnTreatmentFollicular Lymphoma (FL) / Leukemia, Lymphocytic, Chronic, B-Cell / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL)1
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic Lymphocytic Leukemia (CLL) - Refractory1
1, 2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Mantle Cell Lymphoma (MCL)1
1, 2Active Not RecruitingTreatmentDiffuse Large B Cell Lymphoma Relapsed / Refractory Diffuse Large B Cell Lymphoma1
1, 2Active Not RecruitingTreatmentFollicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2Active Not RecruitingTreatmentGraft Versus Host Disease (GVHD)1
1, 2Active Not RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell / Malignant Lymphomas1
1, 2Active Not RecruitingTreatmentLung Cancers1
1, 2Active Not RecruitingTreatmentMalignant Lymphomas1
1, 2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
1, 2Active Not RecruitingTreatmentNeoplasms, Hematologic1
1, 2Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
1, 2CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia / Prolymphocyctic Leukemia / Richter's Transformation / Small Lymphocytic Lymphoma (SLL)1
1, 2CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma (SLL)1
1, 2CompletedTreatmentCancer, Breast / Lung Cancer Non-Small Cell Cancer (NSCLC) / Malignant Neoplasm of Pancreas1
1, 2CompletedTreatmentLeukemias1
1, 2Not Yet RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
1, 2RecruitingTreatmentB-Cell Chronic Lymphocytic Leukemia / Mantle Cell Lymphoma (MCL) / Small Lymphocytic Lymphoma (SLL)2
1, 2RecruitingTreatmentCarcinoma, Colorectal / Colon Diseases / Colorectal Cancers / Malignant Neoplasm of Colon1
1, 2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
1, 2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Mantle Cell Lymphoma (MCL)1
1, 2RecruitingTreatmentColorectal Adenocarcinoma (CRC) / Gastric Adenocarcinoma / Renal Cell Adenocarcinoma / Transitional Cell Carcinoma1
1, 2RecruitingTreatmentGrade 1 Follicular Lymphoma / Grade 2 Follicular Lymphoma / Grade 3a Follicular Lymphoma / Recurrent Follicular Lymphoma / Refractory Follicular Lymphoma1
1, 2RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
1, 2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
1, 2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Malignant Lymphomas / NHL - Non-Hodgkin's Lymphoma1
1, 2RecruitingTreatmentMalignant Neoplasm of Breast / Neoplasms, Breast1
1, 2RecruitingTreatmentMantle Cell Lymphoma (MCL)3
1, 2RecruitingTreatmentMetastatic Renal Cell Cancer / Stage IV Renal Cell Cancer1
1, 2RecruitingTreatmentRefractory Diffuse Large B Cell Lymphoma / Relapsed, Diffuse Large B-cell Lymphoma1
1, 2RecruitingTreatmentRefractory Follicular Lymphoma / Relapsed Follicular Lymphoma1
1, 2RecruitingTreatmentRefractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL)1
1, 2RecruitingTreatmentRefractory/Recurrent Primary Central Nervous System Lymphoma (PCNSL) / Refractory/Recurrent Secondary Central Nervous System Lymphoma (SCNSL)1
1, 2RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
1, 2SuspendedTreatmentRecurrent Plasma Cell Myeloma / Refractory Plasma Cell Myeloma1
1, 2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2Active Not RecruitingTreatmentAdult Patients / Chronic Lymphocyte Leukemia1
2Active Not RecruitingTreatmentCLL (Chronic Lymphocytic Leukemia) / Leukemia, Lymphocytyc / Leukemias / SLL (Small Lymphocytic Lymphoma)1
2Active Not RecruitingTreatmentCarcinoid Tumors / Pancreatic NET1
2Active Not RecruitingTreatmentChronic Lymphocytic Leucemia1
2Active Not RecruitingTreatmentChronic Lymphocytic Leucemia / Chronic Lymphocytic Leukaemia (CLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2Active Not RecruitingTreatmentChronic Lymphocytic Leukemia With 17p Deletion / Small Lymphocytic Lymphoma With 17p Deletion1
2Active Not RecruitingTreatmentFollicular Lymphoma (FL) / Malignant Lymphomas1
2Active Not RecruitingTreatmentIndolent Non-Hodgkin's Lymphomas1
2Active Not RecruitingTreatmentIntraocular Lymphoma / Primary Central Nervous Lymphoma1
2Active Not RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
2Active Not RecruitingTreatmentLeukemia, Prolymphocytic / Recurrent Small Lymphocytic Lymphoma / Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)1
2Active Not RecruitingTreatmentLeukemias1
2Active Not RecruitingTreatmentMetastatic Melanoma / Recurrent Melanoma of the Skin / Stage IV Cutaneous Melanoma AJCC v6 and v71
2Active Not RecruitingTreatmentMultiple Myeloma (MM)2
2Active Not RecruitingTreatmentRecurrent Diffuse Large B-Cell Lymphoma / Refractory Diffuse Large B Cell Lymphoma1
2Active Not RecruitingTreatmentRecurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Refractory Follicular Lymphoma1
2Active Not RecruitingTreatmentWaldenström's Macroglobulinemia (WM)2
2CompletedTreatmentFollicular Lymphoma (FL) / Lymphoma, B-Cell / Non-Hodgkin's Lymphoma (NHL)1
2CompletedTreatmentLeukemias1
2CompletedTreatmentLymphoma, B-Cell / Marginal Zone Lymphoma1
2CompletedTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)1
2CompletedTreatmentMalignant Lymphomas1
2CompletedTreatmentMantle Cell Lymphoma (MCL)3
2Enrolling by InvitationTreatmentB-Cell Chronic Lymphocytic Leukemia / B-Cell Diffuse Lymphoma / Burkitt's Lymphoma / Diffuse Well-differentiated Lymphocytic Lymphoma / Follicular Lymphoma (FL) / Lymphoma, B Cell / Mantle Cell Lymphoma (MCL) / Non-Hodgkin's Lymphoma (NHL) / Small Lymphocytic Lymphoma (SLL) / Waldenström's Macroglobulinemia (WM)1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
2Not Yet RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Ibrutinib Resistance1
2Not Yet RecruitingTreatmentHead and Neck Carcinoma / Squamous Cell Carcinoma of the Head and Neck (SCCHN)1
2Not Yet RecruitingTreatmentHematopoietic/Lymphoid Cancer / Mantle Cell Lymphoma (MCL)2
2Not Yet RecruitingTreatmentLymphoma, B Cell / Mantle Cell Lymphoma (MCL)1
2Not Yet RecruitingTreatmentMantle Cell Lymphoma (MCL)1
2Not Yet RecruitingTreatmentWaldenström's Macroglobulinemia (WM)1
2RecruitingPreventionAcute Biphenotypic Leukemia (ABL) / Acute Lymphoblastic Leukaemias (ALL) / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Hematopoietic Cell Transplantation Recipient / Leukemia Acute Myeloid Leukemia (AML)1
2RecruitingTreatmentAdult B Acute Lymphoblastic Leukemia / Philadelphia Chromosome Positive1
2RecruitingTreatmentAnaphylaxis Food / Food Allergy1
2RecruitingTreatmentBlastoid Variant Mantle Cell Lymphoma / Chronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Follicular Lymphoma / Recurrent Hodgkin Lymphoma / Recurrent Mantle Cell Lymphoma / Refractory Follicular Lymphoma / Refractory Hodgkin Lymphoma / Refractory Mantle Cell Lymphoma1
2RecruitingTreatmentCCND1 Positive / CCND2 Positive / CCND3 Positive / CD20 Positive / Malignant Lymphomas / Mantle Cell Lymphoma (MCL) / Recurrent Mantle Cell Lymphoma / Refractory Mantle Cell Lymphoma1
2RecruitingTreatmentCLL (Chronic Lymphocytic Leukemia) / SLL (Small Lymphocytic Lymphoma)1
2RecruitingTreatmentCentral Nervous System Lymphoma1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemia, Small Lymphocytic / Malignant Neoplasms Stated as Primary Lymphoid Haematopoietic1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias2
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Leukemias / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Primary Lymphoid Haematopoietic Neoplasms / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / SLL1
2RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
2RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Lymphoplasmacytic Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Nodal Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Recurrent Splenic Marginal Zone Lymphoma / Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue / Refractory Follicular Lymphoma / Refractory Lymphoplasmacytic Lymphoma / Refractory Nodal Marginal Zone Lymphoma / Refractory Small Lymphocytic Lymphoma / Refractory Splenic Marginal Zone Lymphoma / Richter's Syndrome / Waldenström's Macroglobulinemia (WM)1
2RecruitingTreatmentChronic Lymphocytic Leukemia (CLL) - Refractory / Chronic, recurrent Lymphocytic Leukemia / Recurrent Small Lymphocytic Lymphoma / Refractory Small Lymphocytic Lymphoma1
2RecruitingTreatmentClassical Hodgkin Lymphoma1
2RecruitingTreatmentClassical Hodgkin Lymphoma / Recurrent Hodgkin Lymphoma / Refractory Hodgkin Lymphoma1
2RecruitingTreatmentContiguous Stage II Mantle Cell Lymphoma / Noncontiguous Stage II Mantle Cell Lymphoma / Stage I Mantle Cell Lymphoma / Stage III Mantle Cell Lymphoma / Stage IV Mantle Cell Lymphoma1
2RecruitingTreatmentEpstein-Barr Virus-positive Diffuse Large B-cell Lymphoma1
2RecruitingTreatmentFollicular Lymphoma (FL)1
2RecruitingTreatmentGastrooesophageal Cancer1
2RecruitingTreatmentHairy Cell Leukemia (HCL) / Hairy Cell Leukemia Variant1
2RecruitingTreatmentHigh Risk Smoldering Multiple Myeloma1
2RecruitingTreatmentLeukemia, Lymphoblastic, Chronic1
2RecruitingTreatmentLymphoma, B-Cell, Marginal Zone1
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL)2
2RecruitingTreatmentLymphoma, Large B-Cell, Diffuse (DLBCL) / Recurrent Diffuse Large B-Cell Lymphoma1
2RecruitingTreatmentMalignant Lymphomas3
2RecruitingTreatmentMantle Cell Lymphoma (MCL)2
2RecruitingTreatmentMetastatic Melanoma / Recurrent Melanoma of the Skin / Stage IV Skin Melanoma1
2RecruitingTreatmentNodular Lymphocyte-Predominant Hodgkin's Lymphoma1
2RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
2RecruitingTreatmentRecurrent Hodgkin Lymphoma / Refractory Hodgkin Lymphoma1
2RecruitingTreatmentRecurrent Mantle Cell Lymphoma / Refractory Mantle Cell Lymphoma1
2RecruitingTreatmentRecurrent Waldenstrom Macroglobulinemia / Refractory Waldenstrom Macroglobulinemia1
2RecruitingTreatmentRelapsed/Refractory Mantle Cell Lymphoma1
2RecruitingTreatmentRichter's Syndrome1
2RecruitingTreatmentStage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia1
2SuspendedTreatmentMetastatic Melanoma / Stage IIIA Skin Melanoma / Stage IIIB Skin Melanoma / Stage IIIC Skin Melanoma / Stage IV Skin Melanoma / Stages III Skin Melanoma1
2SuspendedTreatmentProstate Cancer1
2TerminatedTreatmentAdult B Acute Lymphoblastic Leukemia / Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1 / Recurrent Adult Acute Lymphoblastic Leukemia1
2TerminatedTreatmentAssociated Clonal Hematological Non-Mast-Cell Lineage Disease / Malignant mast cell neoplasm / Systemic Mastocytosis / Systemic mastocytosis with associated hematological neoplasm1
2TerminatedTreatmentLeukemia Acute Myeloid Leukemia (AML)1
2TerminatedTreatmentLymphatic Diseases / Lymphoma, B-Cell1
2TerminatedTreatmentMalignant Lymphomas1
2WithdrawnTreatmentAmyloidosis / Immunoglobulin Light Chain Deposition1
2WithdrawnTreatmentChronic Lymphocytic Leukaemia (CLL) / Chronic, recurrent Lymphocytic Leukemia / Leukemia, Prolymphocytic / Non-Hodgkin's Lymphoma (NHL) / Recurrent Non-Hodgkin Lymphoma / Recurrent Small Lymphocytic Lymphoma / Small Lymphocytic Lymphoma (SLL)1
2WithdrawnTreatmentLung Cancer, Nonsmall Cell, Stage I1
2, 3Enrolling by InvitationTreatmentBrutons Tyrosine Kinase / FLT3-ITD Mutation / Leukemia Acute Myeloid Leukemia (AML)1
3Active Not RecruitingTreatmentAnemias / Chronic Lymphocytic Leukaemia (CLL) / Fever, Sweats, and Hot Flashes / Hepatomegaly / Lymphadenopathy / Lymphocytosis / Small Lymphocytic Lymphoma (SLL) / Splenomegaly / Stage I Chronic Lymphocytic Leukemia / Stage I Small Lymphocytic Lymphoma / Stage II Chronic Lymphocytic Leukemia / Stage II Small Lymphocytic Lymphoma / Stage III Chronic Lymphocytic Leukemia / Stage III Small Lymphocytic Lymphoma / Stage IV Chronic Lymphocytic Leukemia / Stage IV Small Lymphocytic Lymphoma / Thrombocytopenias / Tiredness / Weight Changes1
3Active Not RecruitingTreatmentCD19 Positive / CD20 Positive / CD5 Positive / Stage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Lymphoma, Small-Cell1
3Active Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)2
3Active Not RecruitingTreatmentMalignant Lymphomas2
3Active Not RecruitingTreatmentMantle Cell Lymphoma (MCL)1
3Active Not RecruitingTreatmentPancreatic Adenocarcinoma Metastatic1
3Active Not RecruitingTreatmentRelapsed or Refractory Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)1
3Active Not RecruitingTreatmentWaldenström's Macroglobulinemia (WM)2
3CompletedTreatmentChronic Lymphocytic Leukaemia (CLL) / Small Lymphocytic Lymphoma (SLL)2
3CompletedTreatmentMantle Cell Lymphoma (MCL)1
3Enrolling by InvitationTreatmentChronic Lymphocytic Leukaemia (CLL) / Follicular Lymphoma (FL) / Lymphoma, Large B-Cell, Diffuse (DLBCL) / Mantle Cell Lymphoma (MCL) / Small Lymphocytic Lymphoma (SLL)1
3Not Yet RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
3RecruitingTreatmentActivated B-Cell-Like Diffuse Large B-Cell Lymphoma / B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma / Diffuse Large B-Cell Lymphoma Activated B-Cell Type / Diffuse Large B-Cell Lymphoma, Not Otherwise Specified / High Grade B-Cell Lymphoma, Not Otherwise Specified / Recurrent Burkitt Lymphoma / Recurrent Diffuse Large B-Cell Lymphoma / Refractory Burkitt Lymphoma / Refractory Diffuse Large B Cell Lymphoma1
3RecruitingTreatmentChronic Graft Versus Host Disease1
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)2
3RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL) / Follicular Lymphoma (FL) / Hepatitis B Chronic Infection / Indolent B-cell Lymphomas / Mantle Cell Lymphoma (MCL) / Small Lymphocytic Lymphoma (SLL) / Waldenström's Macroglobulinemia (WM)1
3RecruitingTreatmentGraft Versus Host Disease (GVHD)1
3RecruitingTreatmentGraft Versus Host Disease (GVHD) / Graft-versus-host Disease (GVHD)1
3RecruitingTreatmentLeukemia, Lymphocytic, Chronic, B-Cell1
3RecruitingTreatmentMantle Cell Lymphoma (MCL)2
3RecruitingTreatmentNon-Hodgkin's Lymphoma (NHL)1
3RecruitingTreatmentTreatment Naive Follicular Lymphoma1
3WithdrawnTreatmentMantle Cell Lymphoma (MCL)1
4CompletedTreatmentRelapsed or Refractory Mantle Cell Lymphoma1
4Enrolling by InvitationTreatmentGraft Versus Host Disease (GVHD) / Leukemia, B-Cell / Lymphoma, B-Cell / Non-Hodgkin's Lymphoma (NHL) / Tumors, Solid1
4Not Yet RecruitingOtherLeukemia, Lymphocytic, Chronic, B-Cell1
Not AvailableActive Not RecruitingTreatmentChronic Lymphocytic Leukaemia (CLL)1
Not AvailableApproved for MarketingNot AvailableB-Cell Chronic Lymphocytic Leukemia1
Not AvailableRecruitingNot AvailableChronic Lymphocytic Leukaemia (CLL)2
Not AvailableRecruitingNot AvailableLeukemia, Lymphocytic, Chronic, B-Cell / Mantle Cell Lymphoma (MCL)2
Not AvailableRecruitingTreatmentRecurrent B-Cell Non-Hodgkin Lymphoma / Recurrent Indolent Adult Non-Hodgkin Lymphoma / Refractory B-Cell Non-Hodgkin Lymphoma1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
CapsuleOral140 mg
CapsuleOral140 mg/1
CapsuleOral70 mg/1
Tablet, film coatedOral140 mg/1
Tablet, film coatedOral280 mg/1
Tablet, film coatedOral420 mg/1
Tablet, film coatedOral560 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8476284No2006-12-282026-12-28Us
US8703780No2006-12-282026-12-28Us
US8754090No2011-06-032031-06-03Us
US8497277No2006-12-282026-12-28Us
US9125889No2011-06-032031-06-03Us
US8999999No2011-06-032031-06-03Us
US8697711No2006-12-282026-12-28Us
US8754091No2006-12-282026-12-28Us
US9181257No2006-12-282026-12-28Us
US8957079No2006-12-282026-12-28Us
US8008309No2006-12-282026-12-28Us
US8735403No2006-12-282026-12-28Us
US9296753No2013-10-302033-10-30Us
US7514444No2006-12-282026-12-28Us
US9540382No2013-08-182033-08-18Us
US8952015No2006-12-282026-12-28Us
US9725455No2013-06-032033-06-03Us
US9713617No2013-06-032033-06-03Us
US9795604No2014-10-242034-10-24Us
US9801883No2011-06-032031-06-03Us
US9801881No2011-06-032031-06-03Us
US9814721No2011-06-032031-06-03Us
US8563563No2007-04-262027-04-26Us
US9655857No2016-03-032036-03-03Us
US10004746No2011-06-032031-06-03Us
US10016435No2011-06-032031-06-03Us
US10010507No2016-03-032036-03-03Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)149-158ºCFDA Imbruvica review. (2013)
water solubility0.003 mg/mlFDA Imbruvica review. (2013)
logP3.97FDA Imbruvica review. (2013)
pKa3.74FDA Imbruvica review. (2013)
Predicted Properties
PropertyValueSource
Water Solubility0.0203 mg/mLALOGPS
logP2.76ALOGPS
logP3.63ChemAxon
logS-4.3ALOGPS
pKa (Strongest Acidic)19.7ChemAxon
pKa (Strongest Basic)6.58ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area99.16 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity138.07 m3·mol-1ChemAxon
Polarizability47.84 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether group.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylethers
Direct Parent
Diphenylethers
Alternative Parents
Diarylethers / Phenylpyrazoles / Pyrazolo[3,4-d]pyrimidines / N-acylpiperidines / Phenol ethers / Phenoxy compounds / Aminopyrimidines and derivatives / Imidolactams / Heteroaromatic compounds / Tertiary carboxylic acid amides
show 8 more
Substituents
Diphenylether / Diaryl ether / Phenylpyrazole / N-acyl-piperidine / Pyrazolo[3,4-d]pyrimidine / Pyrazolopyrimidine / Phenoxy compound / Phenol ether / Aminopyrimidine / Piperidine
show 24 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
aromatic ether, N-acylpiperidine, aromatic amine, pyrazolopyrimidine, acrylamides (CHEBI:76612)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately le...
Gene Name
BTK
Uniprot ID
Q06187
Uniprot Name
Tyrosine-protein kinase BTK
Molecular Weight
76280.71 Da
References
  1. Kim ES, Dhillon S: Ibrutinib: a review of its use in patients with mantle cell lymphoma or chronic lymphocytic leukaemia. Drugs. 2015 May;75(7):769-76. doi: 10.1007/s40265-015-0380-3. [PubMed:25802231]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, Cuyckens F, Skee D, Murphy J, Sukbuntherng J, Mannens G: Absorption, metabolism, and excretion of oral (1)(4)C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97. doi: 10.1124/dmd.114.060061. Epub 2014 Dec 8. [PubMed:25488930]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, Cuyckens F, Skee D, Murphy J, Sukbuntherng J, Mannens G: Absorption, metabolism, and excretion of oral (1)(4)C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97. doi: 10.1124/dmd.114.060061. Epub 2014 Dec 8. [PubMed:25488930]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, Cuyckens F, Skee D, Murphy J, Sukbuntherng J, Mannens G: Absorption, metabolism, and excretion of oral (1)(4)C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97. doi: 10.1124/dmd.114.060061. Epub 2014 Dec 8. [PubMed:25488930]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, Cuyckens F, Skee D, Murphy J, Sukbuntherng J, Mannens G: Absorption, metabolism, and excretion of oral (1)(4)C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97. doi: 10.1124/dmd.114.060061. Epub 2014 Dec 8. [PubMed:25488930]
Kind
Protein group
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
References
  1. Scheers E, Leclercq L, de Jong J, Bode N, Bockx M, Laenen A, Cuyckens F, Skee D, Murphy J, Sukbuntherng J, Mannens G: Absorption, metabolism, and excretion of oral (1)(4)C radiolabeled ibrutinib: an open-label, phase I, single-dose study in healthy men. Drug Metab Dispos. 2015 Feb;43(2):289-97. doi: 10.1124/dmd.114.060061. Epub 2014 Dec 8. [PubMed:25488930]

Drug created on May 07, 2015 13:33 / Updated on September 22, 2018 22:36