A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma
- Conditions
- Marginal Zone Lymphoma
- Interventions
- Registration Number
- NCT04416451
- Lead Sponsor
- Memorial Sloan Kettering Cancer Center
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 6
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Age greater than or equal to 18 years
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Histologically confirmed Marginal Zone Lymphoma
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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
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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
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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
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ECOG performance status ≤ 1
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Life expectancy of greater than 2 years
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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
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AST(SGOT)/ALT(SGPT) <3 x institutional upper limit of normal unless elevation is caused by liver involvement with MZL
°OR Creatinine clearance >60 mL/min for patients with creatinine levels above institutional normal (by Cockcroft-Gault estimate or 12-24h creatinine clearance measurements).
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Ability to understand and the willingness to sign a written informed consent document.
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Able to swallow pills
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HIV-positive patients on combination antiretroviral therapy are eligible if their HIV is under adequate control with an antiretroviral regimen that has been stable for > 4 weeks, as long as the CD4 count is > 300. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
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Patients with Hepatitis B surface antibody serum positivity due to prior immunization, as well as those with Hepatitis B core antibody positivity with negative PCR on antiviral therapy will be eligible.
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Patients who have had prior systemic therapy, including rituximab
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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
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Prior treatment with ibrutinib or other BTK inhibitor
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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.
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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
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Lactating or pregnant women
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Participants unwilling to adhere to institutional guidelines for highly effective contraception for 12 months after the last dose of rituximab
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Patients who received moderate or strong CYP3A inhibitors (such as fluconazole, ketoconazole, and clarithromycin) within 7 days prior to the first dose of venetoclax.
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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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Rituximab and Venetoclax Rituximab 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 Rituximab and Venetoclax 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
- Primary Outcome Measures
Name Time Method complete response rate (CRR) 2 years Will be evaluated in this study using the RECIL criteria.
- Secondary Outcome Measures
Name Time Method overall response rates (ORR) 2 years Overall response rate (ORR) will be measured as the number of patients that achieve a PR or CR per RECIL criteria.
Trial Locations
- Locations (8)
Memorial Sloan Kettering Basking Ridge (All Protocol Activities)
🇺🇸Basking Ridge, New Jersey, United States
Memorial Sloan Kettering Monmouth (All protocol activities)
🇺🇸Middletown, New Jersey, United States
Memorial Sloan Kettering Bergen (All protocol Activities)
🇺🇸Montvale, New Jersey, United States
City of Hope Cancer Center (Data collection only)
🇺🇸Duarte, California, United States
Memorial Sloan Kettering Commack (All Protocol Activities)
🇺🇸Commack, New York, United States
Memorial Sloan Kettering Rockville Centre (All Protocol Activities)
🇺🇸Rockville Centre, New York, United States
Memorial Sloan Kettering Westchester (All Protocol Activities)
🇺🇸Harrison, New York, United States
Memorial Sloan Kettering Cancer Center (All Protocol Activities)
🇺🇸New York, New York, United States