Bendamustine, Obinutuzumab, and Venetoclax in Patients With Untreated Mantle Cell Lymphoma

NCT03872180 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 5 other identifiers: IRB00102827NCI-2018-00995Winship4363-18ML40204P30CA138292
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies how well bendamustine, obinutuzumab, and venetoclax work in treating patients with mantle cell lymphoma. Drugs used in chemotherapy, such as bendamustine and venetoclax, 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. Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bendamustine, obinutuzumab, and venetoclax may work better in treating patients with mantle cell lymphoma.

Conditions

CCND1 Positive; Mantle Cell Lymphoma; t(11;14) Positive

Outcome Measures

Primary Outcomes (1)

• Rate of Complete Response at Completion of Induction Therapy With This Combination

  Response will be assessed by positron emission tomography (PET)/computerized tomography (CT) imaging according to the Lugano Classification for response assessment in lymphoma, developed at the 2014 International Conference on Malignant Lymphoma.

  Up to 2.5 years from study start

Secondary Outcomes (5)

• Rate of Minimal Residual Disease (MRD) Negative Complete Response by ClonoSEQ Mantle Cell Lymphoma (MCL) Assay

  Up to 6 years from study start

• Overall Response Rate

  Up to 6 years from study start

• Time to Tumor Progression

  Up to 6 years from study start

• Progression Free Survival (PFS)

  Up to 6 years from study start

• Overall Survival

  Up to 6 years from study start

Study Arms (1)

Venetoclax, bendamustine, obinutuzumab

EXPERIMENTAL

Patients receive venetoclax PO on days 1-28 of course 1 and days 1-10 of subsequent courses, bendamustine IV on days 1 and 2, and obinutuzumab IV on days 1, 8, and 15 of course 1 and day 1 of subsequent courses. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unaccepted toxicity.

Drug: Bendamustine; Biological: Obinutuzumab; Drug: Venetoclax

Interventions

Bendamustine DRUG

Given IV

Also known as: SDX-105

Venetoclax, bendamustine, obinutuzumab

Obinutuzumab BIOLOGICAL

Given IV

Also known as: GA-101, Gazyva, RO5072759

Venetoclax, bendamustine, obinutuzumab

Venetoclax DRUG

Given PO

Also known as: ABT-199, GDC-0199, RG7601, Venclexta, RO5537382

Venetoclax, bendamustine, obinutuzumab

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• Ability and willingness to comply with the requirements of the study protocol
• Histologic diagnosis of mantle cell lymphoma. This diagnosis must be confirmed at the treating center and patients must have this diagnosis confirmed by at least one of the following criteria:
• Fluorescent in situ hybridization (FISH) or conventional cytogenetics positive for t(11;14)
• Cyclin D1 positive by immunohistochemistry
• Documentation by a hematopathologist at the treating institution that there is pathologic evidence of mantle cell lymphoma if neither criteria above are met
• No previous therapy for diagnosis of lymphoma (note that in patients deemed to be high-risk for tumor lysis syndrome or for rapid clinical deterioration due to symptomatic disease by the investigator, a short course of steroids designed to decrease tumor burden is permitted)
• Eastern Cooperative Oncology Group performance status of 0, 1, or 2
• Hemoglobin ≥ 9 g/dL
• Absolute neutrophil count ≥ 1.5 x 10⁹/L
• Platelet count ≥ 75 x 10⁹/L
• Serum creatinine ≤ 2.0 mg/dL or creatinine clearance ≥ 40 mL/min
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN)
• Total bilirubin \< 1.5 x ULN (or ≤ 3 x ULN for patients with documented Gilbert syndrome)
• NOTE: Patients with renal or hepatic impairment that is disease-related (ie, hydronephrosis, hepatic involvement) in the opinion of the investigator but who meet all other eligibility criteria may be considered for enrollment in consultation with the investigational new drug (IND) sponsor, Dr. Jonathon Cohen. Documentation of prior adequate renal/hepatic function and clear association with the disease will be required

You may not qualify if:

• History of other malignancy that could affect compliance with the protocol or interpretation of results
• Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible.
• Individuals in documented remission without treatment for ≥ 2 years prior to enrollment may be included at the discretion of the investigator. Patients with more recently treated low risk prostate cancer, thyroid cancer, or ductal carcinoma in situ (DCIS) who are felt to be at low risk for progression and who are not currently taking any chemotherapy, hormonal therapy or other anti-cancer therapy are eligible. Patients who have been treated and been in remission for \< 2 years must be cleared with the study chair prior to initiating study therapy
• Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient, including renal disease that would preclude chemotherapy administration
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment
• Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin)
• Received strong or moderate cytochrome P450 3A (CYP3A) inhibitors or inducers within 7 days of initiating venetoclax. Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to first dose of venetoclax
• Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis
• Presence of positive test results for hepatitis B virus (HBV), hepatitis B surface antigen (HBsAg), or hepatitis C (HCV) antibody
• Patients who are positive for HCV antibody must be negative for HCV by polymerase chain reaction (PCR) to be eligible for study participation
• Patients with occult or prior HBV infection (defined as positive total hepatitis B core antibody \[HBcAb\] and negative HBsAg) may be included if HBV deoxyribonucleic acid (DNA) is undetectable. These patients must be willing to undergo monthly DNA testing and to remain on hepatitis B prophylaxis during therapy
• Patients with human immunodeficiency virus (HIV) are eligible if they have a cluster of differentiation 4 (CD4) count \> 400 and an undetectable viral load. They must be under the care of an infectious disease physician and have no history of an acquired immune deficiency syndrome (AIDS)-defining illness (except lymphoma)
• Receipt of live-virus vaccines within 28 days prior to the initiation of study treatment or need for live-virus vaccines at any time during study treatment
• Pregnant or lactating, or intending to become pregnant during the study
• Women of childbearing potential must have a negative serum pregnancy test result within 21 days prior to initiation of study drug

Sponsors & Collaborators

• Emory University: lead
• Genentech, Inc.: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (3)

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

Location

Emory Johns Creek Hospital

Johns Creek, Georgia, 30097, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

Bendamustine Hydrochloride; obinutuzumab; venetoclax

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)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jonathon Cohen
• Organization: Emory University Hospital/Winship Cancer Institute

jonathon.cohen@emory.edu

4047781900

Study Officials

• Jonathon B. Cohen, MD, MS

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 13, 2019
• Study Start: April 11, 2019
• Primary Completion: June 6, 2022
• Study Completion: April 30, 2026
• Last Updated: August 6, 2025
• Results First Posted: August 6, 2025

Record last verified: 2025-07

Locations

US (3)