Status:

COMPLETED

Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age

Lead Sponsor:

PrECOG, LLC.

Collaborating Sponsors:

Genentech, Inc.

Conditions:

Mantle Cell Lymphoma

Eligibility:

All Genders

60+ years

Phase:

PHASE2

Brief Summary

Eligible untreated patients will receive single arm venetoclax, bendamustine and rituximab as induction therapy. After 6 cycles, maintenance rituximab may be administered per physician discretion. Ve...

Detailed Description

Mantle cell lymphoma (MCL) is a subtype of Non-Hodgkin Lymphoma (NHL) which is considered incurable with conventional therapy. With an incidence of approximately 70,000 cases diagnosed in the United S...

Eligibility Criteria

Inclusion

  • Inclusion Criteria:
  • Patients must have histologically confirmed (biopsy-proven) diagnosis of mantle cell lymphoma (MCL), with documented cyclin D1 (BCL1) expression by immunohistochemical stains and/or t(11;14) by cytogenetics or Fluorescence In Situ Hybridization (FISH).
  • Patients must have measurable or evaluable disease as defined as a lymph node measuring \>1.5 cm in any dimension or splenomegaly with spleen \>15 cm in craniocaudal dimension.
  • Age ≥ 60 years.
  • No intention to undergo consolidation with high dose chemotherapy and autologous stem cell rescue (Autologous Stem Cell Transplant) in first remission.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
  • Ability to understand and willingness to sign Institutional Review Board (IRB)-approved informed consent.
  • Willing to provide mandatory tissue samples (if sufficient tissue available), bone marrow and blood samples for research purposes.
  • Adequate organ function as measured by the following criteria, obtained ≤ 2 weeks prior to registration:
  • Absolute Neutrophil Count (ANC) ≥ 1000/mm³
  • Hemoglobin ≥ 8 g/dL
  • Platelets ˃75,000/mm³
  • Creatinine clearance ≥ 40 mL/min, calculated with the use of 24-hour creatinine clearance or by Cockcroft-Gault formula
  • Total Bilirubin ≤ 1.5x Upper Limit of Normal (ULN) or ≤ 3x ULN for patients with documented Gilbert's syndrome
  • Aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ≤ 2.5x ULN
  • All females of childbearing potential (not surgically sterilized and between menarche and 1 year post menopause) must have a blood test to rule out pregnancy within 2 weeks prior to registration.
  • Women must not be pregnant or breastfeeding. Females of childbearing potential who are sexually active with a non-sterilized male partner and sexually active men must agree to use 2 methods of adequate contraception (hormonal plus barrier or 2 barrier forms) prior to study entry, for the duration of study participation, and for 12 months after last dose of therapy. Method of contraception must be documented.
  • Patients should not have prior chemotherapy, radiotherapy or immunotherapy for lymphoma.
  • Patients must have no recent (\<1 year) history of malignancy except for the following:
  • adequately treated non-melanoma skin cancer
  • adequately treated Stage I melanoma of the skin
  • in situ cervical cancer
  • low grade prostate adenocarcinoma (Gleason grade ≤ 6) managed with observation and stable for 6 months.
  • Patients should not have known evidence of central nervous system (CNS) lymphoma.
  • Patients must not have received a prior allogeneic stem cell transplant or solid organ transplant (except for cornea) for any indication.
  • Patients must have no active, uncontrolled infections.
  • Patients must not have active hepatitis B or be chronic carriers of hepatitis B. This is defined as patients with hepatitis B surface antigen (HBsAg) positive. Patients with prior exposure to hepatitis B (hepatitis B core antibody (anti-HBc) positive AND HBsAg negative) are allowed with a protective level hepatitis B surface antibody AND a negative hepatitis B viral load by polymerase-chain reaction (PCR).
  • Patients must not have active hepatitis C (HCV) as defined by a hepatitis C viral load detectable by PCR. Patients with a negative HCV antibody are assumed to have a negative HCV viral load. Patients with a positive HCV antibody must have a negative hepatitis C viral load by PCR. Prior treatment for an active HCV infection will be allowed as long as the hepatitis C viral load by PCR is negative.
  • Patients must not have known active Human Immunodeficiency Virus (HIV). Testing not required in absence of clinical suspicion.
  • Patients must not have evidence of significant, uncontrolled concomitant diseases, including psychiatric diseases, that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient.
  • Patients must not have conditions that preclude oral administration or absorption of medications through the GI tract, including but not limited to the inability to swallow pills or malabsorption syndromes.
  • Patients must not have known allergies to both xanthine oxidase inhibitors and rasburicase.
  • Patients must not require the use of warfarin. Blood thinners of other classes are permitted.
  • Patient may not receive the following agents within 7 days prior to the first dose of venetoclax:
  • Strong and moderate CYP3A inhibitors
  • Strong and moderate CYP3A inducers
  • Strong and moderate P-gp inhibitors
  • Patients must not have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges), or star fruit within 3 days prior to the first dose of venetoclax.

Exclusion

    Key Trial Info

    Start Date :

    January 13 2020

    Trial Type :

    INTERVENTIONAL

    Allocation :

    ACTUAL

    End Date :

    July 26 2024

    Estimated Enrollment :

    33 Patients enrolled

    Trial Details

    Trial ID

    NCT03834688

    Start Date

    January 13 2020

    End Date

    July 26 2024

    Last Update

    August 11 2025

    Active Locations (7)

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    Page 1 of 2 (7 locations)

    1

    Carle Cancer Center

    Urbana, Illinois, United States, 61801

    2

    Indiana University Simon Cancer Center

    Indianapolis, Indiana, United States, 46202

    3

    St. Joseph Mercy Hospital Cancer Care Center

    Ann Arbor, Michigan, United States, 48106

    4

    Mayo Clinic

    Rochester, Minnesota, United States, 55905