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 Phase 2 FDA Drug

• 2 other identifiers: 2013-0090NCI-2013-01304
• Study Type: interventional
• Target: 113
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well ibrutinib and rituximab work in treating patients with mantle cell lymphoma that has come back or has not responded to treatment or older patients with newly diagnosed mantle cell lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, may find cancer cells and help kill them. Giving ibrutinib and rituximab may be an effective treatment for mantle cell lymphoma.

Conditions

CCND3 Positive; CD20 Positive; Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Mantle Cell Lymphoma; CCND1 Positive; CCND2 Positive

Outcome Measures

Primary Outcomes (4)

• Overall response (complete response and partial response), assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma

  Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.

  Up to 8 weeks

• Overall response (complete response and partial response) in elderly patients with newly-diagnosed, untreated mantle cell lymphoma, assessed by the International Workshop Standardized Response Criteria for non-Hodgkin lymphoma

  Overall response will be monitored using the Bayesian stopping boundaries calculated based on beta-binomial distribution.

  Up to 8 weeks

• Incidence of toxicity, defined as grade 3 or higher non-hematologic toxicity, grade 3 neutropenia, grade 4 hematologic toxicity, inability to administer full schedule and dose, or inability to receive treatment day 1 of course 2

  Toxicity data will be summarized by frequency tables for all patients.

  Up to 4 weeks

• Incidence of grade 3 or higher non-hematologic toxicity, grade 3 neutropenia, grade 4 hematologic toxicity, inability to administer full schedule and dose, or inability to receive treatment day 1 of course 2 in newly diagnosed elderly patients

  Toxicity data will be summarized by frequency tables for all patients.

  Up to 4 weeks

Secondary Outcomes (9)

• Clinical benefit response (minimal response + overall response rate),

  Up to 6 years

• Duration of response

  Up to 6 years

• Progression-free survival

  Up to 6 years

• Time to progression

  Up to 6 years

• Overall survival

  Up to 6 years

Study Arms (1)

Treatment (ibrutinib, rituximab)

EXPERIMENTAL

Patients receive ibrutinib PO daily on days 1-28 and rituximab IV over 4-8 hours on days 1, 8, 15, and 22 of course 1; on day 1 of courses 3-8; and on day 1 of every other course for all subsequent courses. Treatment with rituximab repeats every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Courses with ibrutinib repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Ibrutinib; Other: Laboratory Biomarker Analysis; Biological: Rituximab

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ibrutinib, rituximab)

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ibrutinib, rituximab)

Rituximab BIOLOGICAL

Given IV

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar IBI301, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, rituximab biosimilar TQB2303, rituximab-abbs, RTXM83, Truxima

Treatment (ibrutinib, rituximab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed/refractory MCL: Confirmed diagnosis of mantle cell lymphoma with cluster of differentiation (CD)20 and cyclin D1 through cyclin D3 positivity in tissue biopsy
• Relapsed/refractory MCL: Patient has relapsed and or refractory MCL and must have received at least one prior treatment regimen for their disease; patient with leukemia phase (peripheral blood involvement), leptomeningeal disease, cerebral spinal fluid (CSF) MCL, central nervous system (CNS) MCL, non-measurable disease, gastrointestinal (GI) MCL, or bone marrow (BM) MCL are also eligible
• Relapsed/refractory MCL: Understand and voluntarily sign an Institutional Review Board (IRB)-approved informed consent form
• Relapsed/refractory MCL: Patients with bone marrow or gastrointestinal (GI) only involvement are acceptable
• Relapsed/refractory MCL: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
• Relapsed/refractory MCL: Absolute neutrophil count (ANC) \>= 500/mm\^3; (patients who have bone marrow infiltration by MCL are eligible if their ANC is \>= 500/mm\^3 \[growth factor allowed\]; these patients should be discussed with either the principal investigator \[PI\] or Co-PI of the study for final approval)
• Relapsed/refractory MCL: Platelet count \>= 30,000/mm\^3 (transfusion to reach platelet count allowed); (patients who have bone marrow infiltration by MCL are eligible if their platelet level is equal to or \> than 15,000/mm\^3; these patients should be discussed with either the PI or Co-PI of the study for final approval)
• Relapsed/refractory MCL: Aspartate transaminase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine transaminase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) \< 2 x upper limit of normal or \< 5 x upper limit of normal if hepatic metastases are present
• Relapsed/refractory MCL: Serum bilirubin \< 1.5 mg/dl
• Relapsed/refractory MCL: Creatinine (Cr) clearance \>= 30 mL/min
• Relapsed/refractory MCL: Patients must be willing to receive transfusions of blood products
• Relapsed/refractory MCL: Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty
• Newly diagnosed MCL: Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy; patients must have never received any prior therapy for their disease
• Newly diagnosed MCL: Understand and voluntarily sign an IRB-approved informed consent form
• Newly diagnosed MCL: Age \> 65 years at the time of signing the informed consent

You may not qualify if:

• Relapsed/refractory MCL: Any serious medical condition that places the patient at unacceptable risk and/or would prevent the subject from signing the informed consent form; examples include but are not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, active infection, active hemorrhage, or psychiatric illness
• Relapsed/refractory MCL: Pregnant or breast feeding females
• Relapsed/refractory MCL: Known human immunodeficiency virus (HIV) infection; patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum hepatitis B antibody); known hepatitis C infection is allowed as long as there is no active disease and is cleared by gastrointestinal (GI) consultation
• Relapsed/refractory MCL: The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent
• Relapsed/refractory MCL: History of stroke or intracranial hemorrhage within 6 months prior to signing the consent
• Relapsed/refractory MCL: Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure or myocardial infarction within 6 months at the time of consent or any class 3 (moderate) or 4 (severe) cardiac disease defined by the New York Heart Association classification
• Relapsed/refractory MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular (AV) block type II, 3rd degree block, bradycardia (\< 50 beats per minute \[bpm\]), or corrected QT (QTc) \> 500 msec
• Relapsed/refractory MCL: Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
• Relapsed/refractory MCL: Prior chemotherapy within 3 weeks, nitrosoureas within 6 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, major surgery within 4 weeks or vaccination with live attenuated vaccines within 4 weeks of the first dose of study drug
• Relapsed/refractory MCL: Prior treatment with ibrutinib
• Relapsed/refractory MCL: Requires anticoagulation with warfarin or equivalent vitamin K antagonist
• Relapsed/refractory MCL: Requires treatment with strong cytochrome P450, family 3, subfamily A, polypeptide 4/5 (CYP3A4/5) inhibitors
• Newly Diagnosed MCL: Any serious medical condition that places the patient at unacceptable risk and/or would prevent the subject from signing the informed consent form; examples include but are not limited to, uncontrolled hypertension, uncontrolled diabetes mellitus, active/symptomatic coronary artery disease, active infection requiring treatment with systemic antibiotics, antiviral or antifungal agents, active hemorrhage, or psychiatric illness
• Newly diagnosed MCL: Known HIV infection; patients with active hepatitis B infection (not including patients with prior hepatitis B vaccination; or positive serum Hepatitis B antibody); known hepatitis C infection is allowed as long as there is no active disease and is cleared by GI consultation
• Newly diagnosed MCL: The patient has a prior or concurrent malignancy that in the opinion of the investigator, presents a greater risk to the patient's health and survival, than of the MCL, within the subsequent 6 months at the time of consent

Sponsors & Collaborators

• National Cancer Institute (NCI): collaborator
• M.D. Anderson Cancer Center: lead

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Jain P, Zhao S, Lee HJ, Hill HA, Ok CY, Kanagal-Shamanna R, Hagemeister FB, Fowler N, Fayad L, Yao Y, Liu Y, Moghrabi OB, Navsaria L, Feng L, Nogueras Gonzalez GM, Xu G, Thirumurthi S, Santos D, Iliescu C, Tang G, Medeiros LJ, Vega F, Avellaneda M, Badillo M, Flowers CR, Wang L, Wang ML. Ibrutinib With Rituximab in First-Line Treatment of Older Patients With Mantle Cell Lymphoma. J Clin Oncol. 2022 Jan 10;40(2):202-212. doi: 10.1200/JCO.21.01797. Epub 2021 Nov 19.

  PMID: 34797699 DERIVED

• Wang ML, Lee H, Chuang H, Wagner-Bartak N, Hagemeister F, Westin J, Fayad L, Samaniego F, Turturro F, Oki Y, Chen W, Badillo M, Nomie K, DeLa Rosa M, Zhao D, Lam L, Addison A, Zhang H, Young KH, Li S, Santos D, Medeiros LJ, Champlin R, Romaguera J, Zhang L. Ibrutinib in combination with rituximab in relapsed or refractory mantle cell lymphoma: a single-centre, open-label, phase 2 trial. Lancet Oncol. 2016 Jan;17(1):48-56. doi: 10.1016/S1470-2045(15)00438-6. Epub 2015 Nov 28.

  PMID: 26640039 DERIVED

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Preetesh Jain

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2013
• First Posted: June 19, 2013
• Study Start: July 15, 2013
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Locations

US (1)