Venetoclax, Lenalidomide and Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

Study Overview
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Brief Summary
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The purpose of this study is to determine if giving an experimental drug called venetoclax in combination with lenalidomide and rituximab is safe and effective for treating people with Mantle Cell Lymphoma (MCL).

Official Title
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Phase I Multi-site Study Evaluating the MTD, Safety and Efficacy of the Combination Venetoclax, Lenalidomide and Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Venetoclax
* Drug: Lenalidomide
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years Diagnosis of mantle cell lymphoma (MCL) established by histologic assessment Laboratory, radiographic, physical exam findings and/or symptoms attributable to MCL ECOG Performance Status (Eastern Cooperative Oncology Group Performance Status: an attempt to quantify cancer patients' general well-being and activities of daily life. The score ranges from 0 to 5 where 0 is asymptomatic and 5 is death) less or equal to 2 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. Men and Women of childbearing potential on appropriate contraception Adequate organ function Ability to understand and the willingness to sign a written informed consent. Ability to swallow oral capsules/tablets Exclusion Criteria: Prior treatment for MCL with chemotherapy Pregnant or breastfeeding women Grade 2 or higher peripheral neuropathy Known history of CNS (Central Nervous System) or leptomeningeal by MCL prior to study enrollment Significant cardiovascular disease Any condition that might significantly impair drug absorption as determined by the investigator Uncontrolled active systemic fungal, bacterial, viral, or other infection, or intravenous anti-infective treatment within 2 weeks before first dose of study drug History of stroke or intracranial hemorrhage within 6 months of 1st dose of study drug Concurrent participation in another clinical trial Subject has received a moderate or strong CYP3A inhibitor or inducer within 1 week prior to treatment initiation. Psychiatric illness or social situations that would limit compliance with study requirements Subject has known positivity to HIV Active infection with Hepatitis B or C virus as determined by a detectable viral load on PCR. Prior malignancy except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or any other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to< 2 years.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Venetoclax, Lenalidomide, Rituximab<br>Rituximab 375 mg/m2 IV day 1, 8, 15, 22 of 1st cycle then on day 1 for cycles 2, 4, 6, 8, 10, 12 Lenalidomide 10 mg day 1-7 of and 15 mg day 8-14 cycle #1. 20 mg PO day day 15-21 of cycle #1 and days 1-21 cycles 2-12. Venetoclax PO days 8 - 28 cycles during cycle 1 only. Starting with ramp-up dose as follows (50 mg x 7 days then 100mg x 7 days then 200 mg x 7 days then 400 mg for remainder of therapy). Will be given days 1-28 at a dose of 400 mg cycle 2-12. | Drug: Venetoclax<br>* PO days 8 - 28 cycles during cycle 1 only. Starting with ramp-up dose as follows (50 mg x 7 days then 100mg x 7 days then 200 mg x 7 days then 400 mg for remainder of therapy). Will be given days 1-28 at a dose of 400 mg cycle 2-12.<br>Drug: Lenalidomide<br>* 10 mg day 1-7 of and 15 mg day 8-14 cycle #1. 20 mg PO day day 15-21 of cycle #1 and days 1-21 cycles 2-12.<br>Drug: Rituximab<br>* 375 mg/m2 IV day 1, 8, 15, 22 of 1st cycle then on day 1 for cycles 2, 4, 6, 8, 10, 12<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of the combination of lenalidomide, venetoclax and rituximab |  | 42 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of patients with a Complete Response (CR) | Response will be assessed by the IRC (Immune-related Response Criteria) and the investigator on the basis of physical examinations and PET and CT scans using the Lugano 2014 criteria, taking into account results of bone marrow examinations for patients with bone marrow involvement at screening | Up to 4 Years | 
| The proportion of patients that respond to treatment | The proportion of patients who achieve either partial or complete response by PET, CT and marrow. Response will be assessed by the IRC and the investigator on the basis of physical examinations and PET and CT scans using the Lugano 2014 criteria, taking into account results of bone marrow examinations for patients with bone marrow involvement at screening | Up to 4 Years |