Rituximab Plus Venetoclax in Front Line Marginal Zone Lymphoma

NCT06510309 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-711
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to see if the combination of rituximab and venetoclax is effective in treating participants with untreated Marginal Zone Lymphoma (MZL). The names of the study drugs involved in this study are:

• Venetoclax (a type of inhibitor)
• Rituximab (a type of antibody)

Conditions

MZL; Lymphoma; Marginal Zone Lymphoma

Keywords

Lymphoma; Marginal Zone Lymphoma; MZL

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CRR)

  Complete Response (CR) rate is defined as the proportion of participants achieving CR during study treatment. CR is defined based on RECIL criteria.

  Up to 24 months

Secondary Outcomes (6)

• Overall response rate (ORR)

  Up to 24 months

• Partial Remission (PR) Rate

  Up to 24 months

• Median Progression Free Survival (PFS)

  Up to 24 months

• Median Overall Survival (OS)

  Up to 36 months

• Median Event Free Survival (EFS)

  Up to 24 months

Study Arms (1)

Rituximab + Venetoclax

EXPERIMENTAL

33 participants will be enrolled and will complete study procedures as follows: * Baseline visit with screening assessments, scans, and tumor and bone marrow biopsies. * Induction Period: * CT/MRI scans at week 4. * Weeks 1 - 4: Predetermined dose of Rituximab 1x weekly. * Weeks 5 - 8: Predetermined dose of Venetoclax 1x daily. * Maintenance Period: * CT/MRI scan on weeks 12, 36, 60, 84, and then every 6 months after week 96. * Predetermined dose of Venetoclax 1x daily for up to week 96, then once every 6 months. * Predetermined dose of Rituximab 1x weekly at weeks 12, 24, 36, and 48. * End of Treatment Visit: CT/MRI scan, tumor biopsy, and bone marrow biopsy. * Follow up: In-clinic visit at 1 year after finishing study drugs.

Drug: Venetoclax; Drug: Rituximab

Interventions

Rituximab DRUG

Anti-CD20 monoclonal antibody, 10mL or 50 mL single-use vials, via intravenous (into the vein) infusion per protocol.

Also known as: Riabni, Ruxience, Truxima, Rituxan, ABP 798, IDEC-C2B8, PF-05280586

Rituximab + Venetoclax

Venetoclax DRUG

B-cell lymphoma inhibitor, tablets taken orally per protocol.

Also known as: ABT-199, GDC-199

Rituximab + Venetoclax

Eligibility Criteria

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

You may qualify if:

• Participants must have histologically confirmed Marginal Zone Lymphoma
• Patients must have measurable disease as defined by at least one lymph node ≥1.5 cm or spleen \> 13 cm
• Patients with intestinal MALT lymphoma must have disease that is detectable by EGD or colonoscopy with biopsy
• Patients with gastric MALT lymphoma must be h. pylori negative. Patients who are h. pylori positive are allowed if they have failed a trial of h. pylori eradication
• Patients with gastric MALT lymphoma who are h. pylori negative or who relapsed/refractory disease after h. pylori eradication must be ineligible form have refused or failed gastric radiation therapy
• Age ≥18 years
• ECOG performance status ≤1
• Life expectancy of greater than 2 years
• Participants must meet the following organ and marrow function as defined below:
• Hemoglobin ≥8.0 g/dL
• absolute neutrophil count ≥1,000 cells/mcL (In the event of documented bone marrow involvement, ANC must be ≥1500 cells/mcL)
• platelets ≥50,000 cells/mm3
• total bilirubin \< 1.5 x institutional upper limit of normal (ULN) (In patients with Gilberts disease or documented liver involvement, total bilirubin \< 3 X ULN will be allowed)
• AST(SGOT)/ALT(SGPT) \< 3 × institutional ULN unless elevation is caused by liver involvement with MZL
• Creatinine within institutional ULN OR creatinine clearance \>60mL/min for patients with creatinine levels above institutional normal (by Cockcroft-Gault estimate or 12-24h creatinine clearance measurements)

You may not qualify if:

• Patients who had prior systemic therapy including rituximab
• Patients who have had prior radiation therapy, with the following exceptions:
• Palliative radiotherapy (RT) is allowed, but must be completed at least 1 week prior to treatment on this study, and prior to any baseline imaging studies or biopsies. Patients must meet criteria for measurable/assessable disease as outlined above after completion of RT.
• Prior RT for gastric MALT is allowed, but must be completed at least 1 week prior to treatment on this study, and prior to any baseline imaging studies or biopsies. Patients must meet criteria for measurable/assessable disease as outlined above after completion of RT.
• Prior treatment with ibrutinib or other BTK inhibitor
• Patients with h. pylori-associated gastric MALT or stage I/II MZL will be excluded unless they are deemed to be unfit for radiation therapy with curative intent.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with uncontrolled hepatitis B or C or HIV infection are ineligible defined as patients with positive serologies and a detectable viral load by PCR.
• Patients with Hep B core ab positivity are allowed provided Hep B PCR is undetectable
• Pregnant women or participants unwilling to adhere to institutional guidelines for highly effective contraception for 12 months after the last dose of rituximab are excluded from this study because of documented risks of rituximab on fetal immunologic development and unknown effects of venetoclax on embryonic development. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued.
• Received moderate or strong CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of venetoclax.
• Received moderate or strong CYP3A inducers (such as rifampin, carbamazepine, phenytoin, St. John's Wort) within 7 days prior to the first dose of venetoclax.

Sponsors & Collaborators

• Gottfried von Keudell, MD PhD: lead
• AbbVie: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma; Lymphoma, B-Cell, Marginal Zone

Interventions

venetoclax; Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin

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

• Gottfried von Keudell, MD, PhD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gottfried von Keudell, MD, PhD

CONTACT

617-667-9920; gkeudell@bidmc.harvard.edu

Dea Hunsicker, PhD

CONTACT

617-975-7425; dhunsick@bidmc.harvard.edu

Study Design

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

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: July 19, 2024
• Study Start: February 11, 2026
• Primary Completion (Estimated): October 1, 2028
• Study Completion (Estimated): October 1, 2031
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Locations

US (1)