a phase ii study using rituximab plus venetoclax in the front line treatment of marginal zone lymphoma

Conditions: Marginal Zone Lymphoma

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.


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: * 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 * 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). * ability to understand and the willingness to sign a written informed consent document. * able to swallow pills * 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. * 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. 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. * 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.

Keywords: rituximab venetoclax 20-115