A Phase II Study of Ibrutinib Plus Rituximab and Lenalidomide in Elderly Patients With Newly Diagnosed MCL
Overview
- Phase
- Phase 2
- Intervention
- Dexamethasone
- Conditions
- CCND1 Positive
- Sponsor
- M.D. Anderson Cancer Center
- Primary Endpoint
- Overall response rate (ORR) per International Workshop Standardization Response Criteria for non-Hodgkin's lymphoma
- Status
- Withdrawn
- Last Updated
- 6 years ago
Overview
Brief Summary
This phase II trial studies how well ibrutinib plus rituximab and lenalidomide work in treating elderly participants with newly diagnosed mantle cell lymphoma. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as rituximab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving ibrutinib plus rituximab and lenalidomide may work better in treating elderly participants with newly diagnosed mantle cell lymphoma.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate the overall response rate (ORR) at 4 months of ibrutinib plus rituximab and lenalidomide in elderly patients with newly-diagnosed, untreated mantle cell lymphoma (MCL). SECONDARY OBJECTIVES: I. To evaluate the toxicity profile of the combination of ibrutinib plus rituximab and lenalidomide in newly diagnosed, untreated 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). Clinical benefit response \[(CBR) = marginal response (MR) + ORR\] will also be evaluated. EXPLORATORY OBJECTIVES: I. Correlative studies will be aimed at confirming the mechanism of action of the combination and to identify predictors of response or resistance to therapy. OUTLINE: Participants receive ibrutinib orally (PO) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab intravenously (IV) on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up at 30 days, every 3 months for 1 year, and every 6 months thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Confirmed diagnosis of MCL with CD20 and cyclin D1 positivity in tissue biopsy.
- •Ki-67 \>= 50%.
- •Patients must have never received any prior systemic therapy for their disease.
- •Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study.
- •Patients should in general have bi-dimensional measurable disease using the Cheson criteria (measurable disease by computed tomography \[CT\] scan defined as at least 1 lesion that measures \>= 1.5 cm in single dimension) (bone marrow or gastrointestinal \[GI\] only involvement is acceptable).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less.
- •Absolute neutrophil count (ANC) \>= 1000/mm\^3 without transfusion support.
- •Platelet count \> 100,000/mm\^
- •Patients who have bone marrow infiltration by MCL are eligible if their platelet level is \>= 50,000 /mm\^3 independent of platelet transfusions.
- •Aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =\< 3 x upper limit of normal.
Exclusion Criteria
- •Any serious medical condition that, in the investigator opinion, 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 intravenous (IV) antibiotics, antiviral or antifungal agents, active hemorrhage, or psychiatric illness in the investigator's opinion places the patient at unacceptable risk and would prevent the subject from signing the informed consent form.
- •Pregnant or breastfeeding females.
- •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. These patients should be optimized by GI consultation for hepatitis B and infectious disease consult for hepatitis C.
- •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.
- •History of stroke or intracranial hemorrhage within 6 months prior to signing the consent.
- •Patients at high-risk for thromboembolic disease, such as those with prior heterotopic ossification (h/o) deep venous thrombosis (DVT).
- •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.
- •Significant screening electrocardiogram (ECG) abnormalities including left bundle branch block, 2nd degree atrioventricular block (AV block) type II, 3rd degree block, bradycardia (\< 50 beats per minute \[bpm\]), or corrected QT (QTc) \> 500 msec.
- •Patients with persistent and uncontrolled atrial fibrillation even if rate controlled.
- •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.
Arms & Interventions
Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
Participants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Dexamethasone
Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
Participants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Ibrutinib
Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
Participants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Lenalidomide
Treatment (ibrutinib, rituximab, lenalidomide, dexamethasone)
Participants receive ibrutinib PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Participants also receive rituximab IV on days 1, 8, 15 and 22 in course 1 and 2, on day 1 of course 3-8, and then on day 1 of every other 28-day course, lenalidomide PO on days 1-21, and dexamethasone PO weekly. Treatment with rituximab repeats every 28 days for 2 years, with lenalidomide for 1 year, and with dexamethasone for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Rituximab
Outcomes
Primary Outcomes
Overall response rate (ORR) per International Workshop Standardization Response Criteria for non-Hodgkin's lymphoma
Time Frame: At 4 months (each cycle is 28 days)
The overall response (complete response + partial response) at four months and toxicity at one month (during course 1) will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey as extended by Thall and Sung. Independence was assumed between or and toxicity, where toxicity is defined as dose-limiting toxicity (DLT) within cycle 1.
Secondary Outcomes
- Overall survival (OS)(Up to 4 years)
- Progression-free survival(Up to 4 years)
- Incidence of adverse events per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.03(At 1 month (cycle 1 is 28 days))