Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04416451
Recruitment Status : Recruiting
First Posted : June 4, 2020
Last Update Posted : July 20, 2022
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Marginal Zone Lymphoma Drug: Rituximab Drug: Venetoclax Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 47 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This is a single-arm, phase II study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Using Rituximab Plus Venetoclax in the Front Line Treatment of Marginal Zone Lymphoma
Actual Study Start Date : May 4, 2021
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: 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
Drug: Rituximab
Induction:Rituximab will be administered per institutional guidelines once per week for 4 weeks at a dose of 375 mg/m^2. Maintenance: 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 (for a total of 4 infusions). On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.

Drug: Venetoclax

Induction: Starting one week after the last induction dose of rituximab (approximately week 5), venetoclax will be administered orally at a flat dose of 100 mg daily and escalating each week to a target dose of 800 mg daily on the following schedule:

  • Week 1: 100 mg
  • Week 2: 200 mg
  • Week 3: 400 mg
  • Week 4: 800 mg Maintenance: Following the 4-week induction phase ramp-up of venetoclax, patients will begin their target dose of 800 mg venetoclax daily and continue this dose during the 24- month maintenance treatment phase. On days when venetoclax and rituximab will both be administered, patients will take venetoclax prior to administration of rituximab.




Primary Outcome Measures :
  1. complete response rate (CRR) [ Time Frame: 2 years ]
    Will be evaluated in this study using the RECIL criteria.


Secondary Outcome Measures :
  1. overall response rates (ORR) [ Time Frame: 2 years ]
    Overall response rate (ORR) will be measured as the number of patients that achieve a PR or CR per RECIL criteria.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04416451


Contacts
Layout table for location contacts
Contact: Andrew Zelenetz, MD, PhD 646-608-3728 zeleneta@mskcc.org
Contact: Gilles Salles, PhD 646-608-4153 sallesg@mskcc.org

Locations
Layout table for location information
United States, California
City of Hope Cancer Center (Data collection only) Recruiting
Duarte, California, United States, 91010
Contact: Tanya Siddiqi, MD    800-826-4673      
United States, New Jersey
Memoral Sloan Kettering Basking Ridge (All Protocol Activities) Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Andrew Zelenetz, MD, PhD    646-608-3728      
Memoral Sloan Kettering Monmouth (All protocol activities) Recruiting
Middletown, New Jersey, United States, 07748
Contact: Andrew Zelenetz, MD, PhD    646-608-3728      
Memorial Sloan Kettering Bergen (All protocol Activities) Recruiting
Montvale, New Jersey, United States, 07645
Contact: Andrew Zelenetz, MD, PhD    646-608-3704      
United States, New York
Memorial Sloan Kettering Commack (All Protocol Activities) Recruiting
Commack, New York, United States, 11725
Contact: Andrew Zelenetz, MD, PhD    646-608-3728      
Memorial Sloan Kettering Westchester (All Protocol Activities) Recruiting
Harrison, New York, United States, 10604
Contact: Andrew Zelenetz, MD, PhD    646-608-3704      
Memorial Sloan Kettering Cancer Center (All Protocol Activities) Recruiting
New York, New York, United States, 10065
Contact: Gottfried von Keudell, MD, PhD    646-608-3704      
Contact: Andrew Zelenetz, MD, PhD    646-608-3728      
Memorial Sloan Kettering Rockville Centre (All Protocol Activities) Recruiting
Rockville Centre, New York, United States, 11570
Contact: Andrew Zelenetz, MD, PhD    646-608-3704      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
AbbVie
Investigators
Layout table for investigator information
Principal Investigator: Andrew Zelenetz, MD, PhD Memorial Sloan Kettering Cancer Center
Additional Information:
Layout table for additonal information
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT04416451    
Other Study ID Numbers: 20-115
First Posted: June 4, 2020    Key Record Dates
Last Update Posted: July 20, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Memorial Sloan Kettering Cancer Center:
Rituximab
Venetoclax
20-115
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Rituximab
Venetoclax
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents