Phase II Trial of Venetoclax and Rituximab as Initial Therapy in Older Patients With Mantle Cell Lymphoma

NCT05025423 | Terminated Phase 2 DMC FDA Drug

• 2 other identifiers: J2146IRB00288478
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is an open-label, single arm phase II study of venetoclax in combination with rituximab in patients over the age of 60 with previously untreated mantle cell lymphoma. The primary objective of the trial is to determine whether the combination of venetoclax with rituximab in this patient population yields a clinically acceptable proportion of overall responses (ORR, assessed by PET/CT with Lugano criteria) without chemotherapy.

Conditions

Mantle Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall response rate (ORR) after four cycles of venetoclax and rituximab.

  The ORR will be the sum of complete (CR) and partial responses (PR)as determined by PET/CT and Lugano criteria. Simon's optimal two-stage design will be used to test the null hypothesis that the true ORR is 50% or less (not considered clinically acceptable).

  120 days

Secondary Outcomes (10)

• Proportion of CR

  120 days

• Proportion of PR

  120 days

• Proportion of stable disease

  120 days

• Proportion of disease progression

  120 days

• Rate of CR after 8 cycles of venetoclax and rituximab

  240 days

Study Arms (1)

venetoclax and rituximab in patients over 60 yrs old with previously untreated mantle cell lymphoma

EXPERIMENTAL

Venetoclax dose escalation for Cycles 1-4. If Complete response (CR) at Cycle 4, continue with cycles 5-12 at fixed venetoclax 400mg dose. If partial response (PR) at Cycle 4, continue with cycles 5-8 at fixed venetoclax 800mg dose. If CR at Cycle 8 after PR, continue with cycles 9-12 at fixed venetoclax 800mg dose. If continued PR at Cycle 8, reduce venetoclax to 400mg and add bendamustine 90 mg/m2.

Drug: Venetoclax Oral Tablet [Venclexta]

Interventions

Venetoclax Oral Tablet [Venclexta] DRUG

Sequential dose levels for Venetoclax dependent on patient response. Fixed doses of 375 mg/m2 rituximab. Fixed dose of Bendamustine 90 mg/m2 added for those with continued PR at Cycle 8

Also known as: rituximab infusion [Rituxan], Bendamustine infusion

venetoclax and rituximab in patients over 60 yrs old with previously untreated mantle cell lymphoma

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must have a histologically confirmed diagnosis of mantle cell lymphoma as defined by the World Health Organization (WHO) classification scheme.
• Age ≥ 60
• Subjects must be previously untreated for mantle cell lymphoma and deemed to require treatment by the treating physician
• ECOG performance status of 0-3
• Subject must have adequate bone marrow\* without growth factor support as follows:
• Absolute Neutrophil Count (ANC) ≥ 1000/μL
• Platelets ≥ 75,000/mm3 (entry platelet count must be independent of transfusion within 14 days of Screening)
• Hemoglobin ≥ 9.0 g/dL \* These criteria may be waived by study investigators if there is evidence of bone marrow involvement by MCL that is believed to be the cause of the cytopenias.
• Subject must have adequate renal, and hepatic function, per laboratory reference range at screening as follows:
• Subject must have adequate renal, and hepatic function, per laboratory reference range at screening as follows:
• Calculated creatinine clearance ≥ 40 mL/min; determined via the Cockcroft-Gault formula.
• AST and ALT ≤ 3.0 × ULN; Bilirubin ≤ 1.5 × ULN\*. Subjects with Gilbert's Syndrome may have a bilirubin \> 1.5 × ULN
• These criteria may be waived by study investigators if abnormal values believed to be due to lymphoma.
• Female subjects must be surgically sterile, postmenopausal (for at least 1 year), or have negative results for a pregnancy test performed as follows:
• At Screening on a serum sample obtained within 14 days prior to the first study drug administration, and

You may not qualify if:

• Subject has blastoid-variant mantle cell lymphoma
• Subject requires immediate cytoreduction as determined by study investigators
• Subject has documented CNS involvement of mantle cell lymphoma
• Subject has Ann Arbor stage I or contiguous stage II mantle cell lymphoma
• Subject has an uncontrolled infection
• Subject has HIV infection
• All subjects will be screened for Hepatitis B (HBsAg, anti-HBs, anti-HBc IgM and total) and Hepatitis C (antibody or RNA). Subjects who are positive for Hepatitis B by HBsAg or DNA as well as subjects positive for Hepatitis C will be excluded. Subjects with anti-HBc positivity and DNA negative may be included but will be required to undergo monthly HBV DNA testing and liver function liver function testing (AST, ALT, alkaline phosphatase, total bilirubin). Patients with HCV antibody positivity and HCV pcr negativity are eligible to be included.
• Subject requires the use of warfarin
• Subject has received immunization with live virus vaccine within 28 days prior to the first dose of study drug
• A female subject is pregnant or breast-feeding

Sponsors & Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lead
• AbbVie: collaborator

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

venetoclax; Rituximab

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)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lode Swinnen, MD

  Johns Hopkins School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Venetoclax dose escalation for Cycles 1-4. If Complete response (CR) at Cycle 4, continue with cycles 5-12 at fixed venetoclax 400mg dose. If partial response (PR) at Cycle 4, continue with cycles 5-8 at fixed venetoclax 800mg dose. If CR at Cycle 8 after PR, continue with cycles 9-12 at fixed venetoclax 800mg dose. If continued PR at Cycle 8, reduce venetoclax to 400mg and add bendamustine 90 mg/m2.

Study Record Dates

• First Submitted: August 26, 2021
• First Posted: August 27, 2021
• Study Start: June 21, 2022
• Primary Completion: May 14, 2025
• Study Completion: May 14, 2025
• Last Updated: June 13, 2025

Record last verified: 2025-06

Locations

US (1)