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

Memorial Sloan Kettering Cancer Center (MSK) logo

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)

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

Trial contacts and locations

0

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Data sourced from clinicaltrials.gov

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