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

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Active, not recruiting; Phase 2

Conditions: Marginal Zone Lymphoma

Treatments: Drug: Venetoclax; Drug: Rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04416451

20-115

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Rituximab and Venetoclax

Experimental group

Description:

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

Treatment:

Drug: Rituximab

Drug: Venetoclax