Non Hodgkin Lymphoma Clinical Trial

Ibrutinib and Rituximab in Treating Patients With Relapsed or Refractory Mantle Cell Lymphoma or Older Patients With Newly Diagnosed Mantle Cell Lymphoma

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.

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Full Description

PRIMARY OBJECTIVES:

I. To evaluate the response rate of ibrutinib plus rituximab in patients with relapsed and/or refractory mantle cell lymphoma (MCL).

II. To evaluate the safety and response rate of ibrutinib plus rituximab in elderly patients (> 65) with newly-diagnosed, untreated MCL.

SECONDARY OBJECTIVES:

I. To further evaluate the toxicity profile of the combination of ibrutinib and rituximab in patients with relapsed and/or refractory MCL.

II. To estimate the overall response rate (ORR); (partial response [PR] or better), the response duration (DOR), progression-free survival (PFS), time to progression (TTP) and overall survival (OS) in patients with relapsed and/or refractory MCL; clinical benefit response (CBR) = (minimal response [MR] + ORR) will also be evaluated.

III. To estimate the response duration, PFS, time to progression (TTP), and OS in elderly patients (> 65) with newly-diagnosed, untreated MCL.

EXPLORATORY OBJECTIVES:

I. To correlate detected gene mutations and changes in gene and/or protein expression with response to treatment.

OUTLINE:

Patients receive ibrutinib orally (PO) daily on days 1-28 and rituximab intravenously (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.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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
Newly diagnosed MCL: Patients should in general have bi-dimensional measurable disease with their biggest tumor less than 10 cm; (bone marrow or gastrointestinal [GI] only involvement is acceptable)
Newly diagnosed MCL: Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less
Newly diagnosed MCL: Absolute neutrophil count (ANC) > 750/mm^3; patients who have bone marrow infiltration by MCL are eligible if their ANC is equal to or > than 500
Newly diagnosed MCL: Platelet count > 50,000/mm^3; patients who have bone marrow infiltration by MCL are eligible if their platelet level is equal to or > than 15,000 /mm^3; (platelet transfusions are allowed; these patients should be discussed with either the PI or Co-PI of the study for final approval)
Newly diagnosed MCL: AST (SGOT) and ALT (SGPT) < 2 x upper limit of normal or < 5 x upper limit of normal if hepatic metastases are present
Newly diagnosed MCL: Uric acid within normal limits (allopurinol is allowed to bring abnormal level to within normal limits)
Newly diagnosed MCL: Serum bilirubin < 1.5 mg/dl
Newly diagnosed MCL: Creatinine (Cr) Clearance >= 30 mL/min
Newly diagnosed MCL: Ki67 protein (Ki67) < 50%
Newly diagnosed MCL: Disease free of prior malignancies of equal to or greater than 6 months with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma "in situ" of the cervix or breast, or other malignancies in remission (including prostate cancer patients in remission from radiation therapy, surgery or brachytherapy), not actively being treated, with a life expectancy > 3 years
Newly diagnosed MCL: Patients must be willing to receive transfusions of blood products
Newly diagnosed MCL: Willing and able to participate in all study related procedures and therapy including swallowing capsules without difficulty

Exclusion Criteria:

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
Newly diagnosed MCL: History of stroke or intracranial hemorrhage within 6 months prior to signing the consent
Newly diagnosed 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
Newly diagnosed MCL: Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree AV block type II, 3rd degree block, bradycardia (< 50 bpm), or QTc > 500 msec
Newly diagnosed 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
Newly diagnosed MCL: Major surgery within 4 weeks or vaccination with live attenuated vaccines within 4 weeks of the first dose of study drug
Newly diagnosed MCL: Prior treatment with ibrutinib
Newly diagnosed MCL: Requires concomitant anticoagulation with warfarin or equivalent vitamin K antagonist
Newly diagnosed MCL: Requires treatment with strong CYP3A4/5 inhibitors
Newly diagnosed MCL: Patients with blastoid and pleomorphic variants
Newly diagnosed MCL: Ki-67 to be equal or more than 50%
Newly diagnosed MCL: Central nervous system lymphoma
Newly diagnosed MCL: Patients with bi-dimensional measurable disease with a tumor >= 10 cm

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

113

Study ID:

NCT01880567

Recruitment Status:

Active, not recruiting

Sponsor:

M.D. Anderson Cancer Center

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There is 1 Location for this study

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M D Anderson Cancer Center
Houston Texas, 77030, United States

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 2

Estimated Enrollment:

113

Study ID:

NCT01880567

Recruitment Status:

Active, not recruiting

Sponsor:


M.D. Anderson Cancer Center

How clear is this clinincal trial information?

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