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

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

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Mantle Cell Lymphoma
• Intervention / Treatment: Drug: Venetoclax; Drug: Lenalidomide; Drug: Rituximab

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48187
      • University of Michgan Comprehensive Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Venetoclax, Lenalidomide, Rituximab; 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; 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: 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.; Drug: 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Michigan Rogel Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 24, 2018
• Primary Completion (Actual): January 20, 2021
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: April 26, 2018
• First Submitted That Met QC Criteria: May 10, 2018
• First Posted (Actual): May 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 19, 2022
• Last Update Submitted That Met QC Criteria: October 18, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide; Venetoclax; Rituximab
• Other Study ID Numbers: UMCC 2018.005; HUM00140979 (Other Identifier: University of Michigan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No