Clinical Trials /

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

NCT03834688

Description:

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. Venetoclax is an oral Bcl-2 family protein inhibitor. It targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with mantle cell lymphoma. Venetoclax may make the cancer cells sensitive to chemotherapy. This may help to slow down the growth of cancer or may cause cancer cells to die. The purpose of this study is to see if venetoclax in combination with bendamustine and rituximab chemotherapy is effective in treating people who have mantle cell lymphoma and to examine the side effects, good and bad, associated with this combination.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age
  • Official Title: Phase II Study of Bendamustine and Rituximab Plus Venetoclax in Untreated Mantle Cell Lymphoma Over 60 Years of Age

Clinical Trial IDs

  • ORG STUDY ID: PrE0405
  • SECONDARY ID: ML40551
  • NCT ID: NCT03834688

Conditions

  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
VenetoclaxGDC-0199, ABT-199, RO5537382Induction
BendamustineBendamustine hydrochlorideInduction
RituximabChimeric anti-CD20 monoclonal antibody, RituxanInduction

Purpose

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. Venetoclax is an oral Bcl-2 family protein inhibitor. It targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with mantle cell lymphoma. Venetoclax may make the cancer cells sensitive to chemotherapy. This may help to slow down the growth of cancer or may cause cancer cells to die. The purpose of this study is to see if venetoclax in combination with bendamustine and rituximab chemotherapy is effective in treating people who have mantle cell lymphoma and to examine the side effects, good and bad, associated with this combination.

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 States (US) per year, the disease is rare.

      This is an open-label phase II study of venetoclax in combination with bendamustine and
      rituximab. Patients will receive induction therapy with venetoclax, bendamustine and
      rituximab for six cycles (1 cycle = 28 days). There will be an interim analysis after 19
      patients are enrolled to evaluate for tumor lysis syndrome (TLS). TLS is caused by the fast
      breakdown of cancer cells which can lead to electrolyte and kidney problems.

      Tumor assessments will be performed after Cycle 3-4 and at end of induction therapy.

      Mandatory pre-treatment tumor tissue sample (i.e., obtained in the course of standard biopsy
      or surgery) will be required for research (if sufficient tissue is available).

      Mandatory bone marrow aspirate and peripheral blood sample will be collected at the end of
      treatment for Minimal Residual Disease (MRD). MRD measures the disease remaining after
      treatment. Optional peripheral blood samples will also be collected for future research.
    

Trial Arms

NameTypeDescriptionInterventions
InductionExperimentalVenetoclax, bendamustine and rituximab as induction therapy for 6 cycles of 28 days.
  • Venetoclax
  • Bendamustine
  • Rituximab

Eligibility Criteria

        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 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.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Complete Response (CR) rate at end of induction
Time Frame:30 months
Safety Issue:
Description:CR assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)

Secondary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame:60 months
Safety Issue:
Description:Number of participants with abnormal laboratory values and/or adverse events with particular attention to TLS related to treatment
Measure:Overall Response Rate (ORR)
Time Frame:60 months
Safety Issue:
Description:ORR assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)
Measure:Progression-Free Survival (PFS)
Time Frame:60 months
Safety Issue:
Description:PFS assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)
Measure:Overall Survival (OS)
Time Frame:60 months
Safety Issue:
Description:OS assessed in accordance with Lymphoma Response Criteria (Cheson Criteria)

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:PrECOG, LLC.

Trial Keywords

  • Venetoclax
  • Bendamustine
  • Rituximab
  • Bcl-2 Family Protein Inhibitor

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