A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma

NCT04416451 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 20-115
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 8

Brief Summary

This study will help researchers understand how effective the combination of venetoclax and rituximab is in treating MZL in people who have not received a previous treatment for their cancer.

Conditions

Marginal Zone Lymphoma

Keywords

Rituximab; Venetoclax; 20-115

Outcome Measures

Primary Outcomes (1)

• complete response rate (CRR)

  Will be evaluated in this study using the RECIL criteria.

  2 years

Secondary Outcomes (1)

• overall response rates (ORR)

  2 years

Study Arms (1)

Rituximab and Venetoclax

EXPERIMENTAL

Patients will be treated with an Induction phase of rituximab 375 mg/m2 weekly for 4 weeks. Patients will undergo restaging imaging after the last of 4 weekly rituximab doses and before beginning venetoclax. Based on post-rituximab restaging studies, patients will be risk-stratified for risk of Tumor Lysis Syndrome (TLS) and treated in the appropriate setting with TLS prophylaxis per institutional TLS guide lines starting at week 5. Oral venetoclax will follow a ramp-up dosing schedule and will be taken daily after 4 weeks of rituximab therapy. Following the 4-week ramped-up phase of venetoclax, patients will begin their target dose of venetoclax and continue for a maximum of 24 months. In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months. Venetoclax may be continued after this period if patient has not achieved a complete remission

Drug: Rituximab; Drug: Venetoclax

Interventions

Rituximab DRUG

Induction:Rituximab will be administered per institutional guidelines once per week for 4 weeks at a dose of 375 mg/m\^2. Maintenance: In addition, patients will receive rituximab 375 mg/m2 starting on day 1 of the maintenance phase and repeated once every 3 months for 12 months (for a total of 4 infusions). On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.

Rituximab and Venetoclax

Venetoclax DRUG

Induction: Starting one week after the last induction dose of rituximab (approximately week 5), venetoclax will be administered orally at a flat dose of 100 mg daily and escalating each week to a target dose of 800 mg daily on the following schedule: * Week 1: 100 mg * Week 2: 200 mg * Week 3: 400 mg * Week 4: 800 mg Maintenance: Following the 4-week induction phase ramp-up of venetoclax, patients will begin their target dose of 800 mg venetoclax daily and continue this dose during the 24- month maintenance treatment phase. On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.

Rituximab and Venetoclax

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years
• 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 have relapsed/refractory disease after h. pylori eradication must be ineligible for, have refused or failed gastric radiation therapy
• ECOG performance status ≤ 1
• Life expectancy of greater than 2 years
• Patients must have normal organ function as defined below:
• Platelet count ≥ 50,000 cells/mm\^3
• Hemoglobin ≥ 8.0 g/dL
• Absolute neutrophil count ≥ 1000 cells/mcL. If there is documented bone marrow involvement, ANC must be \>/= 500 cells/mcL
• Total bilirubin \< 1.5 x upper normal institutional limits. In patients with Gilbert's disease or documented liver involvement, total bilirubin up to 3x ULN will be allowed
• AST(SGOT)/ALT(SGPT) \<3 x institutional upper limit of normal unless elevation is caused by liver involvement with MZL

You may not qualify if:

• Patients who have had prior systemic therapy, including rituximab
• Patients who have had prior radiation therapy, with the following exception:
• °Palliative radiotherapy RT is allowed but must be completed at least 1 week prior to treatment on this study, and prior 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.
• Patients with 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 Hep B core ab positivity are allowed provided Hep B PCR is undetectable
• Lactating or pregnant women
• Participants unwilling to adhere to institutional guidelines for highly effective contraception for 12 months after the last dose of rituximab
• Patients who received moderate or strong CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of venetoclax.
• Patients who 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

• Memorial Sloan Kettering Cancer Center: lead
• AbbVie: collaborator

Study Sites (8)

City of Hope Cancer Center (Data collection only)

Duarte, California, 91010, United States

Location

Memorial Sloan Kettering Basking Ridge (All Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

Location

Memorial Sloan Kettering Monmouth (All protocol activities)

Middletown, New Jersey, 07748, United States

Location

Memorial Sloan Kettering Bergen (All protocol Activities)

Montvale, New Jersey, 07645, United States

Location

Memorial Sloan Kettering Commack (All Protocol Activities)

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

Location

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Rockville Centre (All Protocol Activities)

Rockville Centre, New York, 11570, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Interventions

Rituximab; venetoclax

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; 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

• Andrew Zelenetz, MD, PhD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: This is a single-arm, phase II study.

Study Record Dates

• First Submitted: June 2, 2020
• First Posted: June 4, 2020
• Study Start: May 4, 2021
• Primary Completion: June 1, 2026
• Study Completion: June 1, 2026
• Last Updated: July 2, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

US (8)