Clinical Trials /

Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma

NCT02728531

Description:

Given the established role of high dose cytarabine (HiDAC) combined with rituximab, along with recent data showing the encouraging efficacy of bendamustine, the investigators seek to integrate the synergistic effects of these medicines in alternating cycles as induction therapy prior to autologous stem cell transplant (ASCT). Based on prior experience with bendamustine and rituximab (BR) based induction therapy, the investigators seek to evaluate the efficacy and safety of stem cell mobilization in this pilot study

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma
  • Official Title: A Pilot Study of Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: 201603149
  • NCT ID: NCT02728531

Conditions

  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
BendamustineBendamustine Hydrochloride, TreandaBendamustine, Rituximab, Cytarabine
RituximabRituxanBendamustine, Rituximab, Cytarabine
CytarabineCytosar-U, Tarabine PFSBendamustine, Rituximab, Cytarabine
PegfilgrastimNeulasta, G-CSFBendamustine, Rituximab, Cytarabine
FilgrastimNeupogenBendamustine, Rituximab, Cytarabine

Purpose

Given the established role of high dose cytarabine (HiDAC) combined with rituximab, along with recent data showing the encouraging efficacy of bendamustine, the investigators seek to integrate the synergistic effects of these medicines in alternating cycles as induction therapy prior to autologous stem cell transplant (ASCT). Based on prior experience with bendamustine and rituximab (BR) based induction therapy, the investigators seek to evaluate the efficacy and safety of stem cell mobilization in this pilot study

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Bendamustine, Rituximab, CytarabineExperimentalBendamustine on Days 1 and 2 of Cycles 1, 3, and 5. In Cycle 1, rituximab on Day 1 or 2 at the investigator's discretion. Given on Day 1 of Cycles 2 through 6. On Days 1 and 2 of Cycles 2, 4, and 6, cytarabine will be administered every 12 hours for a total of 4 doses. Growth factor will be administered subcutaneously within 72 hours of completion of each even-numbered cycles of chemotherapy. Leukapheresis will begin when the total WBC ≥ 5000/ μL and continue daily until collection of ≥ 2x106 CD34+ cells/kg (with a maximum of 5 courses of apheresis). Standard of care peripheral blood autologous stem cell harvest will proceed per institutional guidelines and begin during Cycle 6 following rituximab and cytarabine therapy, when the total WBC ≥ 5000/ μL. Collection will continue on a daily basis until collection of ≥ 2x106 CD34+ cells/kg.
  • Bendamustine
  • Rituximab
  • Cytarabine
  • Pegfilgrastim
    • Filgrastim

    Eligibility Criteria

    Inclusion Criteria:

    - Histologically confirmed mantle cell lymphoma with documented expression of CD20 (or CD 19) and cyclin D1 (BCL1) by immunohistochemical stains and/or t (11; 14) by cytogenetics or FISH

    - Eighteen to 65 years of age, inclusive.

    - Presence of evaluable disease by PET imaging per the Lugano classification (Cheson 201418)

    - Eligible for autologous stem cell transplantation.

    - ECOG performance status ≤ 2

    - Normal bone marrow and organ function as defined below:

    - Absolute neutrophil count ≥ 1,000/mcl unless in the opinion of the treating physician, neutropenia is due to splenomegaly or bone marrow involvement

    - Platelets ≥ 100,000/mcl unless in the opinion of the treating physician, thrombocytopenia is due to splenomegaly or bone marrow involvement

    - Total bilirubin ≤ 2 x IULN and AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN except when, in the opinion of the treating physician, is due to direct involvement of lymphoma (e.g., hepatic infiltration or biliary obstruction due to lymphoma) or Gilbert's disease

    - Creatinine ≤ IULN OR creatinine clearance ≥ 40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal

    - Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.

    - Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

    - Negative HIV serology.

    Exclusion Criteria:

    - Any previous chemotherapy or radiation for mantle cell lymphoma. Short course of steroids for symptom relief prior to presentation is permissible.

    - Symptomatic meningeal or parenchymal brain lymphoma.

    - A history of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab, cytarabine, bendamustine or other agents used in the study.

    - Severe concurrent illness, which would limit compliance with study requirements.

    - Subjects with serologic status reflecting active viral hepatitis B or C infection are not eligible. Subjects whoare hepatitis B core antibody positive but antigen negative will need negative polymerase chain reaction (PCR) prior to enrollment. Hepatitis B surface antigen positive or PCR positive patients will be excluded. Subjects who are hepatitis C antibody positive will need negative PCR prior to enrollment. Patients with positive hepatitis C will be excluded.

    - Pregnant and/or breastfeeding. Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days of study entry.

    Maximum Eligible Age:65 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Stem cell mobilization success rate
    Time Frame:Completion of stem cell mobilization (approximately 20 weeks)
    Safety Issue:
    Description:-Stem cell mobilization success is defined as a yield of ≥ 2 x 106 CD34+ stem cells/kg with a maximum of 5 courses of apheresis.

    Secondary Outcome Measures

    Measure:Overall response rate
    Time Frame:Completion of treatment (approximately 18 weeks)
    Safety Issue:
    Description:-Response to treatment is guided based upon the Recommendations for Initial Evaluation, Staging and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.
    Measure:Pre-transplant complete response rate (CRR)
    Time Frame:Completion of treatment (approximately 18 weeks)
    Safety Issue:
    Description:CRR= Complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy. London Deauville score of 1 and 2 in lymph nodes and extra lymphatic sites is considered to represent complete metabolic response. A London Deauville score 3 in the post treatment PET scan may be considered to represent complete metabolic response especially if it is not higher than the surrounding normal physiologic uptake. No evidence of FDG avid disease in the bone marrow No new lesions If the bone marrow was involved by lymphoma before treatment, the infiltrate must have cleared on repeat bone marrow biopsy.
    Measure:Progression-free survival (PFS)
    Time Frame:5 years
    Safety Issue:
    Description:-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
    Measure:Overall survival (OS)
    Time Frame:5 years
    Safety Issue:
    Description:
    Measure:Safety and tolerability of bendamustine and rituximab alternating with cytarabine and rituximab as measured by grades 3 or higher toxicities
    Time Frame:30 days following completion of treatment (approximately 22 weeks)
    Safety Issue:
    Description:The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.

    Details

    Phase:Phase 1
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Washington University School of Medicine

    Trial Keywords

      Last Updated

      February 2, 2017