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

ID: NCT02728531
Status: Recruiting
Phase: Phase 1
Start Date: April 18, 2016
First Submitted: March 30, 2016
Last Updated: February 05, 2018
Results: N/A
Sponsors & Collaborators: Washington University School of Medicine
Location: United States
Conditions: Mantle Cell Lymphoma
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Study Description

Brief Summary

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

Condition or disease Intervention/treatment Phase

Mantle Cell Lymphoma

Drug: Bendamustine
Other Names
Bendamustine Hydrochloride Treanda
Drug: Rituximab
Other Names
Rituxan
Drug: Cytarabine
Other Names
Cytosar-U Tarabine PFS
Drug: Pegfilgrastim
Other Names
Neulasta G-CSF
Procedure: Leukapheresis
Other Names
Drug: Filgrastim
Other Names
Neupogen
Procedure: Autologous stem cell transplant
Other Names
Phase 1

Tracking Information

First Submitted DateMarch 30, 2016
Last Update Posted DateFebruary 05, 2018
Start DateApril 18, 2016
Anticipated Completion DateApril 30, 2023
Primary Completion DateSeptember 30, 2018
Results First Submitted DateN/A
Received Results Disposit DateN/A

Current Primary Outcome Measures

  • Stem cell mobilization success rate [Time Frame: Completion of stem cell mobilization (approximately 20 weeks)]

    -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.

Original Primary Outcome Measures

Not Available

Current Secondary Outcome Measures

  • Overall response rate [Time Frame: Completion of treatment (approximately 18 weeks)]

    -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.

  • Pre-transplant complete response rate (CRR) [Time Frame: Completion of treatment (approximately 18 weeks)]

    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.

  • Progression-free survival (PFS) [Time Frame: 5 years]

    -PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.

  • Overall survival (OS) [Time Frame: 5 years]

  • 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)]

    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.

Original Secondary Outcome Measures

Not Available

Study Design

Brief TitleBendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma
Official TitleA Pilot Study of Bendamustine and Rituximab Alternating With Cytarabine and Rituximab for Untreated Mantle Cell Lymphoma
Brief Summary

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

Study TypeInterventional
Study PhasePhase 1
Estimated Enrollment
15
Allocation
Not Available
Interventional Model
Single Group Assignment
Masking
None (Open Label)
Primary Purpose
Treatment
Conditions
Mantle Cell Lymphoma
Target Follow-Up Duration N/A
Biospecimen:
N/A
Sampling MethodN/A
Study PopulationN/A
Intervention
Drug: Bendamustine

Other Names
Bendamustine Hydrochloride
Treanda
Drug: Rituximab

Other Names
Rituxan
Drug: Cytarabine

Other Names
Cytosar-U
Tarabine PFS
Drug: Pegfilgrastim

Other Names
Neulasta
G-CSF
Procedure: Leukapheresis

Other Names
Drug: Filgrastim

Other Names
Neupogen
Procedure: Autologous stem cell transplant

Other Names
Study Groups/Cohorts
Bendamustine, Rituximab, Cytarabine
Bendamustine 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.

Study Arms
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Bendamustine

Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Rituximab

Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Cytarabine

Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Pegfilgrastim

Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Procedure : Leukapheresis

Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Filgrastim

Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Procedure : Autologous stem cell transplant

Arm Intervention/Treatment
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Bendamustine
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Rituximab
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Cytarabine
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Pegfilgrastim
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Procedure : Leukapheresis
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Drug : Filgrastim
Experimental Bendamustine, Rituximab, Cytarabine
Bendamustine 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.
Procedure : Autologous stem cell transplant

Recruitment Information

Recruitment Status:Recruiting
Enrollment15
Completion DateApril 30, 2023
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.
GenderAll
Age18 Years to 65 Years
Accepts Healthy VolunteersNo
Contacts
Listed Location Countries
United States

Administrative Information

NCT Number:NCT02728531
Other Study ID Numbers
201603149
Has Data Monitoring CommitteeYes
U.S. FDA-regulated Product Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Device Product Not Approved or Cleared by U.S. FDA: No
IPD Sharing Statement
Not Available
Responsible Party,
Study Sponsor
Washington University School of Medicine
Collaborators
Not Available
Investigators
Principal Investigator
Brad S Kahl, M.D.
Washington University School of Medicine