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

Primary Purpose

Mantle Cell Lymphoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bendamustine
Rituximab
Cytarabine
Pegfilgrastim
Leukapheresis
Filgrastim
Autologous stem cell transplant
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bendamustine, Rituximab, Cytarabine

Arm Description

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.

Outcomes

Primary Outcome Measures

Stem cell mobilization success rate
-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

Overall response rate
-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)
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)
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Overall survival (OS)
Safety and tolerability of bendamustine and rituximab alternating with cytarabine and rituximab as measured by grades 3 or higher toxicities
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.

Full Information

First Posted
March 30, 2016
Last Updated
May 25, 2023
Sponsor
Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT02728531
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 18, 2016 (Actual)
Primary Completion Date
January 16, 2019 (Actual)
Study Completion Date
September 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mantle Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bendamustine, Rituximab, Cytarabine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Bendamustine Hydrochloride, Treanda
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Cytosar-U, Tarabine PFS
Intervention Type
Drug
Intervention Name(s)
Pegfilgrastim
Other Intervention Name(s)
Neulasta, G-CSF
Intervention Type
Procedure
Intervention Name(s)
Leukapheresis
Intervention Type
Drug
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
Neupogen
Intervention Type
Procedure
Intervention Name(s)
Autologous stem cell transplant
Primary Outcome Measure Information:
Title
Stem cell mobilization success rate
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.
Time Frame
Completion of stem cell mobilization (approximately 25 weeks)
Secondary Outcome Measure Information:
Title
Overall response rate
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.
Time Frame
Completion of treatment (approximately 24 weeks)
Title
Pre-transplant complete response rate (CRR)
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.
Time Frame
Completion of treatment (approximately 24 weeks)
Title
Progression-free survival (PFS)
Description
-PFS is defined as the duration of time from start of treatment to time of progression or death, whichever occurs first.
Time Frame
5 years
Title
Overall survival (OS)
Time Frame
5 years
Title
Safety and tolerability of bendamustine and rituximab alternating with cytarabine and rituximab as measured by grades 3 or higher toxicities
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.
Time Frame
30 days following completion of treatment (approximately 29 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brad S Kahl, M.D.
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32126141
Citation
Merryman RW, Edwin N, Redd R, Bsat J, Chase M, LaCasce A, Freedman A, Jacobson C, Fisher D, Ng S, Crombie J, Kim A, Odejide O, Davids MS, Brown JR, Jacene H, Cashen A, Bartlett NL, Mehta-Shah N, Ghobadi A, Kahl B, Joyce R, Armand P, Jacobsen E. Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma. Blood Adv. 2020 Mar 10;4(5):858-867. doi: 10.1182/bloodadvances.2019001355.
Results Reference
derived
Links:
URL
http://www.siteman.wustl.edu
Description
Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Learn more about this trial

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

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