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

Memorial Sloan Kettering Cancer Center8 sites in 1 country6 target enrollmentMay 4, 2021

Overview

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.

Registry

clinicaltrials.gov

Start Date

May 4, 2021

End Date

June 1, 2026

Last Updated

10 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Memorial Sloan Kettering Cancer Center

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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:

Exclusion Criteria

•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.

Arms & Interventions

Rituximab and Venetoclax

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

Intervention: Rituximab

Rituximab and Venetoclax

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

Intervention: Venetoclax