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Rituximab/Bendamustine + Rituximab/Cytarabine for Mantle Cell Lymphoma

Primary Purpose

Mantle Cell Lymphoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Bendamustine
Cytarabine
Sponsored by
Dana-Farber Cancer Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Mantle Cell Lymphoma focused on measuring Newly diagnosed

Eligibility Criteria

18 Years - 69 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Mandatory pathologic review of the diagnostic specimen(s) at Brigham and Women's Hospital or Massachusetts General Hospital
  • Measurable disease
  • Candidate for ASCT

Exclusion Criteria:

  • Prior anti-lymphoma therapy
  • Pregnant or breastfeeding
  • Hypersensitivity to rituximab
  • Uncontrolled intercurrent illness
  • Receiving other study agents
  • HIV positive on combination antiretroviral therapy

Sites / Locations

  • Massachusetts General Hospital
  • Brigham and Women's Hospital
  • Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RB/RC

Arm Description

Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to: 2 g/m2 for age >60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity; 1.5 g/m2 for age >60 years old AND creatinine 114.9-176.8 lmol/l, or for age >60 years old AND pre-existing neurotoxicity; 1 g/m2 for age > 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity. Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study.

Outcomes

Primary Outcome Measures

Complete Remission (CR) Rate After 6 Cycles
The CR rate is defined as the proportion of patients who after 6 cycles of therapy achieve complete remission based on the International Working Group (IWG) Criteria (Cheson et al, 1999), using CT scans. CR or CRu (CR unconfirmed) by CT scans was defined by standard IWG criteria, ie resolution of all abnormal adenopathy and organomegaly, and clearance of marrow disease when present at baseline.

Secondary Outcome Measures

1 Year Progression-Free Survival
1-year progression-free survival is the probability of patients remaining alive and progression-free at 1 year from study entry estimated using Kaplan-Meier methods. Disease progression was based on the International Working Group (IWG) Criteria (Cheson et al, 1999).
Autologous Stem Cell Transplant (ASCT) Rate
ASCT rate is the proportion of patients who completed therapy and proceeded to autologous stem cell transplant (ASCT)

Full Information

First Posted
July 15, 2012
Last Updated
June 6, 2023
Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01661881
Brief Title
Rituximab/Bendamustine + Rituximab/Cytarabine for Mantle Cell Lymphoma
Official Title
A Phase II Study of Rituximab/Bendamustine Followed by Rituximab/Cytarabine for Untreated Mantle Cell Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 16, 2012 (Actual)
Primary Completion Date
February 2015 (Actual)
Study Completion Date
March 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Dana-Farber Cancer Institute
Collaborators
Massachusetts General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Mantle cell lymphoma (MCL) is not curable with conventional therapy. This study sought to improve upon standard of care in newly diagnosed, untreated MCL patients who were transplant-eligible using drugs already established as active in MCL. The combination of Rituximab-Bendamustine followed by Rituximab-Cytarabine (RB/RC) was expected to maximize pre-ASCT complete response (CR) rate compared to historical rates approximating 55% with tolerable toxicity.
Detailed Description
This was a PII single-arm design to determine whether the regimen looked promising for further study. Primary Objective • To evaluate the efficacy of an alternating regimen of Rituximab-Bendamustine and Rituximab-Cytarabine (RB/RC) using the CR/Cru rate. Secondary Objectives To assess safety. To estimate the rate of complete remission (CR), unconfirmed CR (CRu), partial remission (PR), stable disease (SD) and progressive disease (PD). To estimate the rate of successful stem cell mobilization after RB/RC in responding patients. To estimate the proportion of patients who can successfully complete the regimen and proceed to autologous stem cell transplantation (ASCT). To estimate the rate of neutrophil and platelet engraftment after ASCT. To estimate the CR/CRu and PR rate for patients with blastoid variant MCL. To estimate the rate of minimal residual disease (MRD)-negativity at treatment completion.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RB/RC
Arm Type
Experimental
Arm Description
Patients received 3 cycles of outpatient RB (rituximab 375 mg/m2 day 1, bendamustine 90 mg/m2 days 1 and 2 of a 4-week cycle), followed by interim CT restaging. Patients with progressive disease (PD) went off study. Those with stable disease (SD) or better went on to receive three cycles of inpatient RC (rituximab 375 mg/m2 day 1, cytarabine 3 g/m2 every 12 h for 4 doses). The cytarabine was dose reduced to: 2 g/m2 for age >60 years old, creatinine 114.9-176.8 lmol/l (for patients ≤60 years old), and pre-existing neurotoxicity; 1.5 g/m2 for age >60 years old AND creatinine 114.9-176.8 lmol/l, or for age >60 years old AND pre-existing neurotoxicity; 1 g/m2 for age > 60 years old AND creatinine 114.9-176.8 lmol/l AND pre-existing neurotoxicity. Stem cell mobilization and collection, ASCT and post-transplantation supportive care were performed per institutional standard and not as part of this study.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Depocyt
Primary Outcome Measure Information:
Title
Complete Remission (CR) Rate After 6 Cycles
Description
The CR rate is defined as the proportion of patients who after 6 cycles of therapy achieve complete remission based on the International Working Group (IWG) Criteria (Cheson et al, 1999), using CT scans. CR or CRu (CR unconfirmed) by CT scans was defined by standard IWG criteria, ie resolution of all abnormal adenopathy and organomegaly, and clearance of marrow disease when present at baseline.
Time Frame
Disease was assessed after three- and six-cycles of therapy, up to approximately 25 weeks. All patients completed 6 cycles of therapy with a cycle duration of 28 days.
Secondary Outcome Measure Information:
Title
1 Year Progression-Free Survival
Description
1-year progression-free survival is the probability of patients remaining alive and progression-free at 1 year from study entry estimated using Kaplan-Meier methods. Disease progression was based on the International Working Group (IWG) Criteria (Cheson et al, 1999).
Time Frame
Disease was assessed after three- and six-cycles of therapy and in long-term follow-up per standard practice every 6 months until the earliest of relapse, death or 5 years. Median follow-up in this study cohort was 13 months.
Title
Autologous Stem Cell Transplant (ASCT) Rate
Description
ASCT rate is the proportion of patients who completed therapy and proceeded to autologous stem cell transplant (ASCT)
Time Frame
All patients were followed for continuation to ASCT upon completion of induction therapy. Patients usually proceed to ASCT within 3 months of completing induction.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
69 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Mandatory pathologic review of the diagnostic specimen(s) at Brigham and Women's Hospital or Massachusetts General Hospital Measurable disease Candidate for ASCT Exclusion Criteria: Prior anti-lymphoma therapy Pregnant or breastfeeding Hypersensitivity to rituximab Uncontrolled intercurrent illness Receiving other study agents HIV positive on combination antiretroviral therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe Armand, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute
Official's Role
Study Chair
Facility Information:
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02113
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
26729345
Citation
Armand P, Redd R, Bsat J, Mayuram S, Giardino A, Fisher DC, LaCasce AS, Jacobson C, Davids MS, Brown JR, Weng L, Wilkins J, Faham M, Freedman AS, Joyce R, Jacobsen ED. A phase 2 study of Rituximab-Bendamustine and Rituximab-Cytarabine for transplant-eligible patients with mantle cell lymphoma. Br J Haematol. 2016 Apr;173(1):89-95. doi: 10.1111/bjh.13929. Epub 2016 Jan 5.
Results Reference
result
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
result

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Rituximab/Bendamustine + Rituximab/Cytarabine for Mantle Cell Lymphoma

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