Dose Finding Study of Ibrutinib Plus Lenalidomide / Rituximab in Relapsed or Refractory Mantle Cell Lymphoma
NCT ID: NCT02446236
Last Updated: 2025-01-30
Study Results
Results available
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
Recruitment Status
ACTIVE_NOT_RECRUITING
Clinical Phase
PHASE1
Total Enrollment
27 participants
Study Classification
INTERVENTIONAL
Study Start Date
2015-06-18
Study Completion Date
2025-10-31
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
This is a dose-escalation to determine the MTD and/or RPII for combinations of ibrutinib (PCI-32765) plus lenalidomide/rituximab in patients with relapsed/refractory mantle cell lymphoma.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
A Study of the Bruton's Tyrosine Kinase Inhibitor Ibrutinib Given in Combination With Bendamustine and Rituximab in Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT01776840
Mantle Cell Lymphoma
COMPLETED
PHASE3
An Open Label Treatment Use Protocol for Ibrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma
NCT01833039
Relapsed or Refractory Mantle Cell Lymphoma
APPROVED_FOR_MARKETING
A Trial of Ibrutinib, Lenalidomide and Rituximab for Patients With Relapsed/Refractory Mantle Cell Lymphoma
NCT02460276
Relapsed/Refractory Mantle Cell Lymphoma
COMPLETED
PHASE2
Lenalidomide, Ibrutinib, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma That Is Metastatic or Cannot Be Removed by Surgery
NCT02160015
Recurrent Chronic Lymphocytic Leukemia
Recurrent Small Lymphocytic Lymphoma
Refractory Chronic Lymphocytic Leukemia
+1 more
ACTIVE_NOT_RECRUITING
PHASE1
A Study of Ibrutinib With Rituximab in Relapsed or Refractory Mantle Cell Lymphoma
NCT05564052
Lymphoma, Mantle-Cell
COMPLETED
PHASE2
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Mantle cell lymphoma (MCL) is a relatively rare subtype (3% to 6% (Zhou, 2008) of mature B cell non-Hodgkin lymphomas (NHL), with a median age at diagnosis in mid to late 60's, a male predominance (3/1) and typically advanced stage presentation though only about 1/3 of patients are truly symptomatic at baseline (Armitage, 1998). Although significant controversies remain in the management of MCL, all would agree that the challenges associated with MCL, particularly the poor results with standard chemotherapy and frequent chemoresistance have pushed the community to be more innovative and active in clinical research. Hence the median OS has clearly improved over the last 3 decades (from 2-3y to \>5y) (Goy, 2011a), thanks to deeper responses obtained with intensive regimens in younger patients (an early CR translates into clearly better outcome) and also better salvage therapies with now MCL being the only lymphoma with 4 new biologicals approved (3 in the US and 1 in EU).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Mantle Cell Lymphoma
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
Allocation Method
NA
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Dose Escalation Study
Ibrutinib 560 mg/daily rituximab 375mg/m2 IV Day 1 Lenalidomide 10-25 mg PO days 1-21
Group Type
EXPERIMENTAL
Lenalidomide
Intervention Type
DRUG
Dose escalation of lenalidomide. Patients will receive 10, 15, 20, or 25 mg PO days 1-21
Ibrutinib
Intervention Type
DRUG
560 mg PO daily
Rituximab
Intervention Type
DRUG
375 mg/m2 IV Day 1
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Lenalidomide
Dose escalation of lenalidomide. Patients will receive 10, 15, 20, or 25 mg PO days 1-21
Intervention Type
DRUG
Ibrutinib
560 mg PO daily
Intervention Type
DRUG
Rituximab
375 mg/m2 IV Day 1
Intervention Type
DRUG
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Revlimid
Imbruvica
Rituxan
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Age greater than or equal to 18 years.
* Histologically or cytologically confirmed diagnosis of MCL.
* Relapsed or refractory MCL patients who have received at least one prior therapy are eligible. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible.
* Presence of at least one lymph node evaluable or mass measurable for response.
* Eastern Cooperative Oncology Group Performance Status greater than 2.
* Platelets \> 75,000/μL and absolute neutrophils count (ANC) \> 1,000/μL within 14 days of study registration (unless the treating physician deems the neutropenia is related to bone marrow involvement, then an ANC of \> 750/mm 3 is allowed)
* Normal renal function defined as serum creatinine less than 2.
* Recovery from any previous treatment therapy.
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
* All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
* Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
* Ability to understand, and willingness to sign, a written informed consent document.
* Able to take aspirin (81 or 325 mg) daily as prophylactic anti-coagulation (patients intolerant to ASA may use low molecular weight heparin).
* Normal organ and bone marrow function parameter:
Laboratory tests Required value WBC \>3000/μL\* Absolute neutrophils count \>1,000/μL\* Platelets \>75,000/μL Total bilirubin \< 1.5Within normal institutional limits AST (SGOT) and ALT (SGPT) \<3 x institutional upper limit of normal Creatinine or creatinine clearance \<1.5 within normal institutional limits \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated by Cockcroft-Gault formula)
* Histologically or cytologically confirmed diagnosis of MCL.
* Relapsed or refractory MCL patients who have received at least one prior therapy are eligible. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible.
* Presence of at least one lymph node evaluable or mass measurable for response.
* Eastern Cooperative Oncology Group Performance Status greater than 2.
* Platelets \> 75,000/μL and absolute neutrophils count (ANC) \> 1,000/μL within 14 days of study registration (unless the treating physician deems the neutropenia is related to bone marrow involvement, then an ANC of \> 750/mm 3 is allowed)
* Normal renal function defined as serum creatinine less than 2.
* Recovery from any previous treatment therapy.
* Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test
* All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of the REMS® program.
* Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
* Ability to understand, and willingness to sign, a written informed consent document.
* Able to take aspirin (81 or 325 mg) daily as prophylactic anti-coagulation (patients intolerant to ASA may use low molecular weight heparin).
* Normal organ and bone marrow function parameter:
Laboratory tests Required value WBC \>3000/μL\* Absolute neutrophils count \>1,000/μL\* Platelets \>75,000/μL Total bilirubin \< 1.5Within normal institutional limits AST (SGOT) and ALT (SGPT) \<3 x institutional upper limit of normal Creatinine or creatinine clearance \<1.5 within normal institutional limits \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated by Cockcroft-Gault formula)
Exclusion Criteria
* Concomitant use of warfarin or other Vit K antagonists
* Central nervous system (CNS) involvement by lymphoma at time of enrollment.
* Other medical conditions that would potentially interfere with patient participation in this trial.
* A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix (unless for other tumor type patient was treated with curative intent at least 2 years previously.)
* Known human immunodeficiency virus (HIV-1) infection or chronic hepatitis B, or C (Hep B serology positive without active infection will be eligible)
* Active, clinically serious infection \> CTCAE grade 2. Patients may be eligible upon resolution of the infection.
* Major surgery or significant traumatic injury within 28 days of the first dose of study drug.
* Use of any other standard chemotherapy, radiation therapy, or experimental drug therapy for the treatment of MCL within 21 days of starting treatment or 5 half life times (whatever is shorter)
* Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association (NYHA) criteria:
* History of uncontrolled or symptomatic angina
* History of uncontrolled arrhythmias
* Myocardial infarction \< 6 months from study entry
* Uncontrolled or symptomatic congestive heart failure
* Ejection fraction below the institutional normal limit
* Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient
* Patients unwilling or unable to comply with the protocol.
* Central nervous system (CNS) involvement by lymphoma at time of enrollment.
* Other medical conditions that would potentially interfere with patient participation in this trial.
* A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix (unless for other tumor type patient was treated with curative intent at least 2 years previously.)
* Known human immunodeficiency virus (HIV-1) infection or chronic hepatitis B, or C (Hep B serology positive without active infection will be eligible)
* Active, clinically serious infection \> CTCAE grade 2. Patients may be eligible upon resolution of the infection.
* Major surgery or significant traumatic injury within 28 days of the first dose of study drug.
* Use of any other standard chemotherapy, radiation therapy, or experimental drug therapy for the treatment of MCL within 21 days of starting treatment or 5 half life times (whatever is shorter)
* Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association (NYHA) criteria:
* History of uncontrolled or symptomatic angina
* History of uncontrolled arrhythmias
* Myocardial infarction \< 6 months from study entry
* Uncontrolled or symptomatic congestive heart failure
* Ejection fraction below the institutional normal limit
* Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient
* Patients unwilling or unable to comply with the protocol.
Minimum Eligible Age
18 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Hackensack Meridian Health
OTHER
Sponsor Role
lead
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Responsibility Role
SPONSOR
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Andre Goy, MD
Role: PRINCIPAL_INVESTIGATOR
Hackensack Meridian Health
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
The Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Site Status
Countries
Review the countries where the study has at least one active or historical site.
United States
References
Explore related publications, articles, or registry entries linked to this study.
Ansell SM, Inwards DJ, Rowland KM Jr, Flynn PJ, Morton RF, Moore DF Jr, Kaufmann SH, Ghobrial I, Kurtin PJ, Maurer M, Allmer C, Witzig TE. Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group. Cancer. 2008 Aug 1;113(3):508-14. doi: 10.1002/cncr.23580.
Reference Type
BACKGROUND
Armitage JO. Management of mantle cell lymphoma. Oncology (Williston Park). 1998 Oct;12(10 Suppl 8):49-55.
Reference Type
BACKGROUND
Caballero D, Campo E, Lopez-Guillermo A, Martin A, Arranz-Saez R, Gine E, Lopez A, Gonzalez-Barca E, Canales MA, Gonzalez-Diaz M, Orfao A. Clinical practice guidelines for diagnosis, treatment, and follow-up of patients with mantle cell lymphoma. Recommendations from the GEL/TAMO Spanish Cooperative Group. Ann Hematol. 2013 Sep;92(9):1151-79. doi: 10.1007/s00277-013-1783-4. Epub 2013 May 29.
Reference Type
BACKGROUND
Corral LG, Kaplan G. Immunomodulation by thalidomide and thalidomide analogues. Ann Rheum Dis. 1999 Nov;58 Suppl 1(Suppl 1):I107-13. doi: 10.1136/ard.58.2008.i107. No abstract available.
Reference Type
BACKGROUND
Crane E, List A. Immunomodulatory drugs. Cancer Invest. 2005;23(7):625-34. doi: 10.1080/07357900500283101.
Reference Type
BACKGROUND
Davies F, Baz R. Lenalidomide mode of action: linking bench and clinical findings. Blood Rev. 2010 Nov;24 Suppl 1:S13-9. doi: 10.1016/S0268-960X(10)70004-7.
Reference Type
BACKGROUND
Dredge K, Horsfall R, Robinson SP, Zhang LH, Lu L, Tang Y, Shirley MA, Muller G, Schafer P, Stirling D, Dalgleish AG, Bartlett JB. Orally administered lenalidomide (CC-5013) is anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res. 2005 Jan;69(1-2):56-63. doi: 10.1016/j.mvr.2005.01.002.
Reference Type
BACKGROUND
Fisher RI, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Stadtmauer EA, O'Connor OA, Shi H, Boral AL, Goy A. Multicenter phase II study of bortezomib in patients with relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2006 Oct 20;24(30):4867-74. doi: 10.1200/JCO.2006.07.9665. Epub 2006 Sep 25.
Reference Type
BACKGROUND
Geisler CH, Kolstad A, Laurell A, Andersen NS, Pedersen LB, Jerkeman M, Eriksson M, Nordstrom M, Kimby E, Boesen AM, Kuittinen O, Lauritzsen GF, Nilsson-Ehle H, Ralfkiaer E, Akerman M, Ehinger M, Sundstrom C, Langholm R, Delabie J, Karjalainen-Lindsberg ML, Brown P, Elonen E; Nordic Lymphoma Group. Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group. Blood. 2008 Oct 1;112(7):2687-93. doi: 10.1182/blood-2008-03-147025. Epub 2008 Jul 14.
Reference Type
BACKGROUND
Goy A, Sinha R, Williams ME, Kalayoglu Besisik S, Drach J, Ramchandren R, Zhang L, Cicero S, Fu T, Witzig TE. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013 Oct 10;31(29):3688-95. doi: 10.1200/JCO.2013.49.2835. Epub 2013 Sep 3.
Reference Type
BACKGROUND
Goy A, Younes A, McLaughlin P, Pro B, Romaguera JE, Hagemeister F, Fayad L, Dang NH, Samaniego F, Wang M, Broglio K, Samuels B, Gilles F, Sarris AH, Hart S, Trehu E, Schenkein D, Cabanillas F, Rodriguez AM. Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma. J Clin Oncol. 2005 Feb 1;23(4):667-75. doi: 10.1200/JCO.2005.03.108. Epub 2004 Dec 21.
Reference Type
BACKGROUND
Goy A, Bernstein SH, Kahl BS, Djulbegovic B, Robertson MJ, de Vos S, Epner E, Krishnan A, Leonard JP, Lonial S, Nasta S, O'Connor OA, Shi H, Boral AL, Fisher RI. Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study. Ann Oncol. 2009 Mar;20(3):520-5. doi: 10.1093/annonc/mdn656. Epub 2008 Dec 12.
Reference Type
BACKGROUND
Goy A. Are we improving the survival of patients with mantle cell lymphoma: if so, what is the explanation? Leuk Lymphoma. 2011 Oct;52(10):1828-30. doi: 10.3109/10428194.2011.604753. Epub 2011 Aug 24. No abstract available.
Reference Type
BACKGROUND
Goy A, Kahl B. Mantle cell lymphoma: the promise of new treatment options. Crit Rev Oncol Hematol. 2011 Oct;80(1):69-86. doi: 10.1016/j.critrevonc.2010.09.003. Epub 2010 Dec 17.
Reference Type
BACKGROUND
Habermann TM, Lossos IS, Justice G, Vose JM, Wiernik PH, McBride K, Wride K, Ervin-Haynes A, Takeshita K, Pietronigro D, Zeldis JB, Tuscano JM. Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma. Br J Haematol. 2009 May;145(3):344-9. doi: 10.1111/j.1365-2141.2009.07626.x. Epub 2009 Feb 24.
Reference Type
BACKGROUND
Hendriks RW, Yuvaraj S, Kil LP. Targeting Bruton's tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014 Apr;14(4):219-32. doi: 10.1038/nrc3702.
Reference Type
BACKGROUND
Herman SE, Gordon AL, Hertlein E, Ramanunni A, Zhang X, Jaglowski S, Flynn J, Jones J, Blum KA, Buggy JJ, Hamdy A, Johnson AJ, Byrd JC. Bruton tyrosine kinase represents a promising therapeutic target for treatment of chronic lymphocytic leukemia and is effectively targeted by PCI-32765. Blood. 2011 Jun 9;117(23):6287-96. doi: 10.1182/blood-2011-01-328484. Epub 2011 Mar 21.
Reference Type
BACKGROUND
Hernandez-Ilizaliturri FJ, Reddy N, Holkova B, Ottman E, Czuczman MS. Immunomodulatory drug CC-5013 or CC-4047 and rituximab enhance antitumor activity in a severe combined immunodeficient mouse lymphoma model. Clin Cancer Res. 2005 Aug 15;11(16):5984-92. doi: 10.1158/1078-0432.CCR-05-0577.
Reference Type
BACKGROUND
Hess G, Herbrecht R, Romaguera J, Verhoef G, Crump M, Gisselbrecht C, Laurell A, Offner F, Strahs A, Berkenblit A, Hanushevsky O, Clancy J, Hewes B, Moore L, Coiffier B. Phase III study to evaluate temsirolimus compared with investigator's choice therapy for the treatment of relapsed or refractory mantle cell lymphoma. J Clin Oncol. 2009 Aug 10;27(23):3822-9. doi: 10.1200/JCO.2008.20.7977. Epub 2009 Jul 6.
Reference Type
BACKGROUND
Hoster E, Dreyling M, Klapper W, Gisselbrecht C, van Hoof A, Kluin-Nelemans HC, Pfreundschuh M, Reiser M, Metzner B, Einsele H, Peter N, Jung W, Wormann B, Ludwig WD, Duhrsen U, Eimermacher H, Wandt H, Hasford J, Hiddemann W, Unterhalt M; German Low Grade Lymphoma Study Group (GLSG); European Mantle Cell Lymphoma Network. A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma. Blood. 2008 Jan 15;111(2):558-65. doi: 10.1182/blood-2007-06-095331. Epub 2007 Oct 25.
Reference Type
BACKGROUND
Katzenberger T, Petzoldt C, Holler S, Mader U, Kalla J, Adam P, Ott MM, Muller-Hermelink HK, Rosenwald A, Ott G. The Ki67 proliferation index is a quantitative indicator of clinical risk in mantle cell lymphoma. Blood. 2006 Apr 15;107(8):3407. doi: 10.1182/blood-2005-10-4079. No abstract available.
Reference Type
BACKGROUND
LaCasce AS, Vandergrift JL, Rodriguez MA, Abel GA, Crosby AL, Czuczman MS, Nademanee AP, Blayney DW, Gordon LI, Millenson M, Vanderplas A, Lepisto EM, Zelenetz AD, Niland J, Friedberg JW. Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL Database. Blood. 2012 Mar 1;119(9):2093-9. doi: 10.1182/blood-2011-07-369629. Epub 2012 Jan 10.
Reference Type
BACKGROUND
Leonard JP, Jung SH, Johnson J, Pitcher BN, Bartlett NL, Blum KA, Czuczman M, Giguere JK, Cheson BD. Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). J Clin Oncol. 2015 Nov 1;33(31):3635-40. doi: 10.1200/JCO.2014.59.9258. Epub 2015 Aug 24.
Reference Type
BACKGROUND
Lopez-Girona A, Heintel D, Zhang LH, Mendy D, Gaidarova S, Brady H, Bartlett JB, Schafer PH, Schreder M, Bolomsky A, Hilgarth B, Zojer N, Gisslinger H, Ludwig H, Daniel T, Jager U, Chopra R. Lenalidomide downregulates the cell survival factor, interferon regulatory factor-4, providing a potential mechanistic link for predicting response. Br J Haematol. 2011 Aug;154(3):325-36. doi: 10.1111/j.1365-2141.2011.08689.x. Epub 2011 Jun 24.
Reference Type
BACKGROUND
Lyman GH, Khorana AA, Kuderer NM, Lee AY, Arcelus JI, Balaban EP, Clarke JM, Flowers CR, Francis CW, Gates LE, Kakkar AK, Key NS, Levine MN, Liebman HA, Tempero MA, Wong SL, Prestrud AA, Falanga A; American Society of Clinical Oncology Clinical Practice. Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013 Jun 10;31(17):2189-204. doi: 10.1200/JCO.2013.49.1118. Epub 2013 May 13.
Reference Type
BACKGROUND
Marriott JB, Clarke IA, Dredge K, Muller G, Stirling D, Dalgleish AG. Thalidomide and its analogues have distinct and opposing effects on TNF-alpha and TNFR2 during co-stimulation of both CD4(+) and CD8(+) T cells. Clin Exp Immunol. 2002 Oct;130(1):75-84. doi: 10.1046/j.1365-2249.2002.01954.x.
Reference Type
BACKGROUND
O'Brien SM. Update on ibrutinib. Clin Adv Hematol Oncol. 2013 Nov;11(11):735-7. No abstract available.
Reference Type
BACKGROUND
Ponader S, Chen SS, Buggy JJ, Balakrishnan K, Gandhi V, Wierda WG, Keating MJ, O'Brien S, Chiorazzi N, Burger JA. The Bruton tyrosine kinase inhibitor PCI-32765 thwarts chronic lymphocytic leukemia cell survival and tissue homing in vitro and in vivo. Blood. 2012 Feb 2;119(5):1182-9. doi: 10.1182/blood-2011-10-386417. Epub 2011 Dec 16.
Reference Type
BACKGROUND
Qian Z, Zhang L, Cai Z, Sun L, Wang H, Yi Q, Wang M. Lenalidomide synergizes with dexamethasone to induce growth arrest and apoptosis of mantle cell lymphoma cells in vitro and in vivo. Leuk Res. 2011 Mar;35(3):380-6. doi: 10.1016/j.leukres.2010.09.027. Epub 2010 Nov 2.
Reference Type
BACKGROUND
Ramsay AG, Clear AJ, Kelly G, Fatah R, Matthews J, Macdougall F, Lister TA, Lee AM, Calaminici M, Gribben JG. Follicular lymphoma cells induce T-cell immunologic synapse dysfunction that can be repaired with lenalidomide: implications for the tumor microenvironment and immunotherapy. Blood. 2009 Nov 19;114(21):4713-20. doi: 10.1182/blood-2009-04-217687. Epub 2009 Sep 28.
Reference Type
BACKGROUND
Rickert RC. New insights into pre-BCR and BCR signalling with relevance to B cell malignancies. Nat Rev Immunol. 2013 Aug;13(8):578-91. doi: 10.1038/nri3487.
Reference Type
BACKGROUND
Romaguera JE, Fayad L, Rodriguez MA, Broglio KR, Hagemeister FB, Pro B, McLaughlin P, Younes A, Samaniego F, Goy A, Sarris AH, Dang NH, Wang M, Beasley V, Medeiros LJ, Katz RL, Gagneja H, Samuels BI, Smith TL, Cabanillas FF. High rate of durable remissions after treatment of newly diagnosed aggressive mantle-cell lymphoma with rituximab plus hyper-CVAD alternating with rituximab plus high-dose methotrexate and cytarabine. J Clin Oncol. 2005 Oct 1;23(28):7013-23. doi: 10.1200/JCO.2005.01.1825. Epub 2005 Sep 6.
Reference Type
BACKGROUND
Rosenwald A, Wright G, Wiestner A, Chan WC, Connors JM, Campo E, Gascoyne RD, Grogan TM, Muller-Hermelink HK, Smeland EB, Chiorazzi M, Giltnane JM, Hurt EM, Zhao H, Averett L, Henrickson S, Yang L, Powell J, Wilson WH, Jaffe ES, Simon R, Klausner RD, Montserrat E, Bosch F, Greiner TC, Weisenburger DD, Sanger WG, Dave BJ, Lynch JC, Vose J, Armitage JO, Fisher RI, Miller TP, LeBlanc M, Ott G, Kvaloy S, Holte H, Delabie J, Staudt LM. The proliferation gene expression signature is a quantitative integrator of oncogenic events that predicts survival in mantle cell lymphoma. Cancer Cell. 2003 Feb;3(2):185-97. doi: 10.1016/s1535-6108(03)00028-x.
Reference Type
BACKGROUND
Rummel MJ, Niederle N, Maschmeyer G, Banat GA, von Grunhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Durk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W; Study group indolent Lymphomas (StiL). Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet. 2013 Apr 6;381(9873):1203-10. doi: 10.1016/S0140-6736(12)61763-2. Epub 2013 Feb 20.
Reference Type
BACKGROUND
Satterthwaite AB, Willis F, Kanchanastit P, Fruman D, Cantley LC, Helgason CD, Humphries RK, Lowell CA, Simon M, Leitges M, Tarakhovsky A, Tedder TF, Lesche R, Wu H, Witte ON. A sensitized genetic system for the analysis of murine B lymphocyte signal transduction pathways dependent on Bruton's tyrosine kinase. Proc Natl Acad Sci U S A. 2000 Jun 6;97(12):6687-92. doi: 10.1073/pnas.110146697.
Reference Type
BACKGROUND
Schafer PH, Gandhi AK, Loveland MA, Chen RS, Man HW, Schnetkamp PP, Wolbring G, Govinda S, Corral LG, Payvandi F, Muller GW, Stirling DI. Enhancement of cytokine production and AP-1 transcriptional activity in T cells by thalidomide-related immunomodulatory drugs. J Pharmacol Exp Ther. 2003 Jun;305(3):1222-32. doi: 10.1124/jpet.102.048496. Epub 2003 Mar 20.
Reference Type
BACKGROUND
Shaffer AL, Rosenwald A, Staudt LM. Lymphoid malignancies: the dark side of B-cell differentiation. Nat Rev Immunol. 2002 Dec;2(12):920-32. doi: 10.1038/nri953.
Reference Type
BACKGROUND
Tam CS, Khouri IF. Autologous and allogeneic stem cell transplantation: rising therapeutic promise for mantle cell lymphoma. Leuk Lymphoma. 2009 Aug;50(8):1239-48. doi: 10.1080/10428190903026518.
Reference Type
BACKGROUND
Vegliante MC, Palomero J, Perez-Galan P, Roue G, Castellano G, Navarro A, Clot G, Moros A, Suarez-Cisneros H, Bea S, Hernandez L, Enjuanes A, Jares P, Villamor N, Colomer D, Martin-Subero JI, Campo E, Amador V. SOX11 regulates PAX5 expression and blocks terminal B-cell differentiation in aggressive mantle cell lymphoma. Blood. 2013 Mar 21;121(12):2175-85. doi: 10.1182/blood-2012-06-438937. Epub 2013 Jan 15.
Reference Type
BACKGROUND
Verhelle D, Corral LG, Wong K, Mueller JH, Moutouh-de Parseval L, Jensen-Pergakes K, Schafer PH, Chen R, Glezer E, Ferguson GD, Lopez-Girona A, Muller GW, Brady HA, Chan KW. Lenalidomide and CC-4047 inhibit the proliferation of malignant B cells while expanding normal CD34+ progenitor cells. Cancer Res. 2007 Jan 15;67(2):746-55. doi: 10.1158/0008-5472.CAN-06-2317.
Reference Type
BACKGROUND
Vose JM. Mantle cell lymphoma: 2012 update on diagnosis, risk-stratification, and clinical management. Am J Hematol. 2012 Jun;87(6):604-9. doi: 10.1002/ajh.23176.
Reference Type
BACKGROUND
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.
Reference Type
BACKGROUND
Wang M, Fowler N, Wagner-Bartak N, Feng L, Romaguera J, Neelapu SS, Hagemeister F, Fanale M, Oki Y, Pro B, Shah J, Thomas S, Younes A, Hosing C, Zhang L, Newberry KJ, Desai M, Cheng N, Badillo M, Bejarano M, Chen Y, Young KH, Champlin R, Kwak L, Fayad L. Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Leukemia. 2013 Sep;27(9):1902-9. doi: 10.1038/leu.2013.95. Epub 2013 Apr 2.
Reference Type
BACKGROUND
Wiernik PH, Lossos IS, Tuscano JM, Justice G, Vose JM, Cole CE, Lam W, McBride K, Wride K, Pietronigro D, Takeshita K, Ervin-Haynes A, Zeldis JB, Habermann TM. Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin's lymphoma. J Clin Oncol. 2008 Oct 20;26(30):4952-7. doi: 10.1200/JCO.2007.15.3429. Epub 2008 Jul 7.
Reference Type
BACKGROUND
Witzig TE, Vose JM, Zinzani PL, Reeder CB, Buckstein R, Polikoff JA, Bouabdallah R, Haioun C, Tilly H, Guo P, Pietronigro D, Ervin-Haynes AL, Czuczman MS. An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma. Ann Oncol. 2011 Jul;22(7):1622-1627. doi: 10.1093/annonc/mdq626. Epub 2011 Jan 12.
Reference Type
BACKGROUND
Witzig TE, Geyer SM, Ghobrial I, Inwards DJ, Fonseca R, Kurtin P, Ansell SM, Luyun R, Flynn PJ, Morton RF, Dakhil SR, Gross H, Kaufmann SH. Phase II trial of single-agent temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol. 2005 Aug 10;23(23):5347-56. doi: 10.1200/JCO.2005.13.466. Epub 2005 Jun 27.
Reference Type
BACKGROUND
Wodarz D, Garg N, Komarova NL, Benjamini O, Keating MJ, Wierda WG, Kantarjian H, James D, O'Brien S, Burger JA. Kinetics of CLL cells in tissues and blood during therapy with the BTK inhibitor ibrutinib. Blood. 2014 Jun 26;123(26):4132-5. doi: 10.1182/blood-2014-02-554220. Epub 2014 May 14.
Reference Type
BACKGROUND
Woyach JA, Smucker K, Smith LL, Lozanski A, Zhong Y, Ruppert AS, Lucas D, Williams K, Zhao W, Rassenti L, Ghia E, Kipps TJ, Mantel R, Jones J, Flynn J, Maddocks K, O'Brien S, Furman RR, James DF, Clow F, Lozanski G, Johnson AJ, Byrd JC. Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy. Blood. 2014 Mar 20;123(12):1810-7. doi: 10.1182/blood-2013-09-527853. Epub 2014 Jan 10.
Reference Type
BACKGROUND
Wu A, Scheffler MR. Multi-dose phamacokinetics and safety of CC-5013 in 15 multiple myeloma patients. J Clin Oncol.;22:141s, 2004
Reference Type
BACKGROUND
Wu L, Adams M, Carter T, Chen R, Muller G, Stirling D, Schafer P, Bartlett JB. lenalidomide enhances natural killer cell and monocyte-mediated antibody-dependent cellular cytotoxicity of rituximab-treated CD20+ tumor cells. Clin Cancer Res. 2008 Jul 15;14(14):4650-7. doi: 10.1158/1078-0432.CCR-07-4405.
Reference Type
BACKGROUND
Zhang L, Qian Z, Cai Z, Sun L, Wang H, Bartlett JB, Yi Q, Wang M. Synergistic antitumor effects of lenalidomide and rituximab on mantle cell lymphoma in vitro and in vivo. Am J Hematol. 2009 Sep;84(9):553-9. doi: 10.1002/ajh.21468.
Reference Type
BACKGROUND
Zhou X, Teegala S, Huen A, Ji Y, Fayad L, Hagemeister FB, Gladish G, Vadhan-Raj S. Incidence and risk factors of venous thromboembolic events in lymphoma. Am J Med. 2010 Oct;123(10):935-41. doi: 10.1016/j.amjmed.2010.05.021.
Reference Type
BACKGROUND
Zhou Y, Wang H, Fang W, Romaguer JE, Zhang Y, Delasalle KB, Kwak L, Yi Q, Du XL, Wang M. Incidence trends of mantle cell lymphoma in the United States between 1992 and 2004. Cancer. 2008 Aug 15;113(4):791-8. doi: 10.1002/cncr.23608.
Reference Type
BACKGROUND
Zhu D, Corral LG, Fleming YW, Stein B. Immunomodulatory drugs Revlimid (lenalidomide) and CC-4047 induce apoptosis of both hematological and solid tumor cells through NK cell activation. Cancer Immunol Immunother. 2008 Dec;57(12):1849-59. doi: 10.1007/s00262-008-0512-7. Epub 2008 Apr 8.
Reference Type
BACKGROUND
Zinzani PL, Vose JM, Czuczman MS, Reeder CB, Haioun C, Polikoff J, Tilly H, Zhang L, Prandi K, Li J, Witzig TE. Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. Ann Oncol. 2013 Nov;24(11):2892-7. doi: 10.1093/annonc/mdt366. Epub 2013 Sep 12.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
Pro 5444
Identifier Type: -
Identifier Source: org_study_id
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.
Ibrutinib, Rituximab, and Consolidation Chemotherapy in Treating Young Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT02427620
ACTIVE_NOT_RECRUITING
PHASE2
Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma
NCT01880567
ACTIVE_NOT_RECRUITING
PHASE2
Ibrutinib Plus Rituximab and Lenalidomide in Treating Elderly Participants With Newly Diagnosed Mantle Cell Lymphoma
NCT03232307
WITHDRAWN
PHASE2
A Multi-Center Study of Ibrutinib in Combination With MEDI4736 in Subjects With Relapsed or Refractory Lymphomas
NCT02401048
COMPLETED
PHASE1/PHASE2
Lenalidomide and Rituximab in the Treatment of Relapsed Mantle Cell Lymphoma (MCL) and Diffuse Large B-Cell Lymphoma
NCT00294632
COMPLETED
PHASE1/PHASE2
Ibrutinib in Combination With Lenalidomide and Rituximab in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
NCT02077166
COMPLETED
PHASE1/PHASE2
Study of Ibrutinib in Combination With Bendamustine and Rituximab for Patients With Relapsed/Refractory Aggressive BCL
NCT02747732
UNKNOWN
PHASE2
Rituxan/Bendamustine/PCI-32765 in Relapsed DLBCL, MCL, or Indolent Non-Hodgkin's Lymphoma
NCT01479842
ACTIVE_NOT_RECRUITING
PHASE1
Phase 2 Study to Assess Activity & Safety of Front-line Ibrutinib + Rituximab in Unfit Chronic Lymphocytic Leukemia
NCT02232386
COMPLETED
PHASE2
Ibrutinib Combined With Rituximab for Treatment of Relapsed Refractory MYD88 and CD79A/B (or CD79B Alone) DLBCL Who Have Received at Least Two Prior Therapies
NCT04994626
UNKNOWN
PHASE2
Bendamustine/Lenalidomide/Rituximab: Combination as a Second-Line Therapy for 1st Relapsed-Refractory MCL
NCT01737177
COMPLETED
PHASE2
Ibrutinib in Combination With Rituximab in Patients With Indolent Clinical Forms of MCL
NCT02682641
ACTIVE_NOT_RECRUITING
PHASE2
Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib in Participants With Relapsed or Refractory Mantle Cell Lymphoma
NCT02169180
COMPLETED
PHASE2
Ibrutinib With Rituximab and Lenalidomide for Patients With Recurrent/Refractory Primary or Secondary Central Nervous System Lymphoma (PCNSL/SCNSL)
NCT03703167
ACTIVE_NOT_RECRUITING
PHASE1
A Study of the MALT1 Inhibitor JNJ-67856633 and Ibrutinib in Combination in B-cell NHL and CLL
NCT04876092
COMPLETED
PHASE1
Ibrutinib After Intensive Induction in Treating Patients With Previously Untreated Mantle Cell Lymphoma
NCT02242097
ACTIVE_NOT_RECRUITING
PHASE2
Observational Study of Lenalidomide in Subjects With Mantle Cell Lymphoma Who Failed Ibrutinib Treatment
NCT02341781
COMPLETED
Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Hematologic Malignancies
NCT01871675
COMPLETED
PHASE1
Ibrutinib in Treating Participants With Untreated High Risk Smoldering Mantle Cell Lymphoma
NCT03282396
ACTIVE_NOT_RECRUITING
PHASE2
LOC-R01 Study of Lenalidomide and Ibrutinib in Association With Rituximab-Methotrexate Procarbazine Vincristin (R-MPV)
NCT04446962
ACTIVE_NOT_RECRUITING
PHASE1/PHASE2
Safety Study of CC-292 and Rituximab in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
NCT01744626
COMPLETED
PHASE1
A Study of PCI-32765 (Ibrutinib) in Combination With Either Bendamustine and Rituximab or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Participants With Previously Treated Indolent Non-Hodgkin Lymphoma
NCT01974440
COMPLETED
PHASE3
A Study of Acalabrutinib in Combination With Rituximab Versus Ibrutinib Versus Acalabrutinib in Subjects With Relapsed or Refractory Mantle Cell Lymphoma
NCT02735876
WITHDRAWN
PHASE3
Study of Ibrutinib in Combination With Rituximab in Previously Untreated Subjects With Follicular Lymphoma
NCT01980654
COMPLETED
PHASE2
A Study of Zilovertamab and Ibrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma
NCT05431179
WITHDRAWN
PHASE3