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A Phase I Study of Bendamustine and Melphalan Conditioning and Autologous Stem Cell Transplantation for Treatment of Multiple Myeloma and Relapsed/Refractory B-cell Lymphoma in Elderly Patients

Primary Purpose

Lymphoma

Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rituximab
bendamustine
melphalan
Autologous Stem Cell Transplantation (ASCT)
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring Rituximab, Bendamustine, Melphalan, Autologous Stem Cell Transplantation (ASCT), 17-373

Eligibility Criteria

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

Inclusion Criteria:

Phase I eligibility:

  • Any patient with multiple myeloma B-cell non-Hodgkin lymphoma would be eligible for phase I portion of the study.

Dose expansion eligibility:

  • Histologically confirmed diagnosis of multiple myeloma or rel/ref DLBCL, or diffuse large B cell lymphoma transformed from an indolent lymphoma Since the endpoint of the Phase I portion is safety, any patient with myeloma or B-cell NHL can be enrolled. For dose expansion study patients with myeloma and B-NHL will be analyzed separately. The PFS endpoint varies greatly amongst different types of lymphoma. In order to accurately interpret the survival data as secondary endpoint, a homogeneous cohort of patients with DLBCL will be evaluated. DLBCL is the most aggressive B-NHL with limited options. Other B-NHL's are generally more indolent and have more options available to them.

Additional eligibility for both the phase I and dose expansion cohort:

  • Patients between the ages of 65 to 69 years old with a Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) score of 3 or higher.
  • Any patient age 70 years old or older, irrespective of their Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) score.
  • KPS ≥ 70
  • Males must agree to use an acceptable form of contraception per institutional practices.
  • Complete or partial response to salvage chemotherapy by IWG Working Group Criteria
  • Cardiac ejection fraction of ≥ 45%
  • Hemoglobin-adjusted diffusing capacity of carbon monoxide (DLCO) of ≥45%
  • Creatinine clearance of ≥50 mL/min
  • Completion of most recent salvage therapy within 8 weeks of enrollment
  • Direct bilirubin ≤2.0 mg/dL in the absence of suspected Gilbert's disease (if Gilbert's disease is suspected, the total bilirubin must be ≤3.0 mg/dL), and AST ≤ 2.5 ULN.

Exclusion Criteria:

  • In Lymphoma: Disease progression by IWG Working Group Criteria since last therapy
  • Patients with history of CNS involvement
  • Prior autologous (only in lymphoma) or allogeneic stem cell transplantation
  • Patients who have failed bendamustine-based regimen previously
  • Patients within 6 months of MI and stroke will be excluded

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

rituximab, bendamustine & melphalan and ASCT

Arm Description

This is a phase I study of rituximab, bendamustine and melphalan (RBM) conditioning followed by ASCT in elderly patients with B-cell NHL. Conditioning regimen consist of rituximab 375 mg/m2 on days -11 and -4, bendamustine 160 mg/m2 intravenously on days -3 and -2; melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0. The conditioning timeline can be modified if there are patient scheduling conflicts. Patients who are deemed inevaluable will be replaced for the primary objective. Patients will be considered inevaluable if they don't receive one dose of conditioning regimen and are removed from the study.

Outcomes

Primary Outcome Measures

Dose limiting toxicities (DLT)
are defined as grade > 3, non-hematologic toxicity related to treatment excluding grade 3 nausea or vomiting responsive to anti-emetic treatment, grade 3 diarrhea responding to anti-diarrheal treatment, grade 3 fatigue, grade 3 skin rash responsive to topical or systemic steroids, grade 3 fevers (> 40 degrees Celsius for < 24 hours) and alopecia per CTCAE

Secondary Outcome Measures

Full Information

First Posted
November 21, 2017
Last Updated
January 10, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT03352765
Brief Title
A Phase I Study of Bendamustine and Melphalan Conditioning and Autologous Stem Cell Transplantation for Treatment of Multiple Myeloma and Relapsed/Refractory B-cell Lymphoma in Elderly Patients
Official Title
A Phase I Study of Bendamustine and Melphalan Conditioning and Autologous Stem Cell Transplantation for Treatment of Multiple Myeloma and Relapsed/Refractory B-cell Lymphoma in Elderly Patients
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 20, 2017 (Actual)
Primary Completion Date
November 2023 (Anticipated)
Study Completion Date
November 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

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

5. Study Description

Brief Summary
This study is testing a combination of chemo-immuno therapy called RBM. RBM consists of combination of drugs: rituximab, bendamustine, and melphalan followed by reinfusion of the participants own stem cells which is called autologous stem cell transplant (ASCT). Compared to the standard BEAM regimen, this RBM regimen may or may not be less effective in lymphoma, but will likely have fewer side effects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
Rituximab, Bendamustine, Melphalan, Autologous Stem Cell Transplantation (ASCT), 17-373

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
This is a phase I single arm, open label trial
Masking
None (Open Label)
Allocation
N/A
Enrollment
28 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
rituximab, bendamustine & melphalan and ASCT
Arm Type
Experimental
Arm Description
This is a phase I study of rituximab, bendamustine and melphalan (RBM) conditioning followed by ASCT in elderly patients with B-cell NHL. Conditioning regimen consist of rituximab 375 mg/m2 on days -11 and -4, bendamustine 160 mg/m2 intravenously on days -3 and -2; melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0. The conditioning timeline can be modified if there are patient scheduling conflicts. Patients who are deemed inevaluable will be replaced for the primary objective. Patients will be considered inevaluable if they don't receive one dose of conditioning regimen and are removed from the study.
Intervention Type
Drug
Intervention Name(s)
rituximab
Intervention Description
rituximab 375 mg/m2 on days -11 and -4, The second dose of rituximab (day -4) is administered 7 days after the first dose (day -11), +/- 1 day. Rituximab may be administered by a local oncologist. If the participant has a CD20 negative tumor, rituximab can be omitted from the conditioning regimen.
Intervention Type
Drug
Intervention Name(s)
bendamustine
Intervention Description
bendamustine 160 mg/m2 intravenously on days -3 and -2
Intervention Type
Drug
Intervention Name(s)
melphalan
Intervention Description
melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0.
Intervention Type
Procedure
Intervention Name(s)
Autologous Stem Cell Transplantation (ASCT)
Intervention Description
reinfusion of autologous stem cells on day 0.
Primary Outcome Measure Information:
Title
Dose limiting toxicities (DLT)
Description
are defined as grade > 3, non-hematologic toxicity related to treatment excluding grade 3 nausea or vomiting responsive to anti-emetic treatment, grade 3 diarrhea responding to anti-diarrheal treatment, grade 3 fatigue, grade 3 skin rash responsive to topical or systemic steroids, grade 3 fevers (> 40 degrees Celsius for < 24 hours) and alopecia per CTCAE
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Phase I eligibility: Any patient with multiple myeloma B-cell non-Hodgkin lymphoma would be eligible for phase I portion of the study. Dose expansion eligibility: Histologically confirmed diagnosis of multiple myeloma or rel/ref DLBCL, or diffuse large B cell lymphoma transformed from an indolent lymphoma Since the endpoint of the Phase I portion is safety, any patient with myeloma or B-cell NHL can be enrolled. For dose expansion study patients with myeloma and B-NHL will be analyzed separately. The PFS endpoint varies greatly amongst different types of lymphoma. In order to accurately interpret the survival data as secondary endpoint, a homogeneous cohort of patients with DLBCL will be evaluated. DLBCL is the most aggressive B-NHL with limited options. Other B-NHL's are generally more indolent and have more options available to them. Additional eligibility for both the phase I and dose expansion cohort: Patients between the ages of 65 to 69 years old with a Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) score of 3 or higher. Any patient age 70 years old or older, irrespective of their Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) score. KPS ≥ 70 Males must agree to use an acceptable form of contraception per institutional practices. Complete or partial response to salvage chemotherapy by IWG Working Group Criteria Cardiac ejection fraction of ≥ 45% Hemoglobin-adjusted diffusing capacity of carbon monoxide (DLCO) of ≥45% Creatinine clearance of ≥50 mL/min Completion of most recent salvage therapy within 8 weeks of enrollment Direct bilirubin ≤2.0 mg/dL in the absence of suspected Gilbert's disease (if Gilbert's disease is suspected, the total bilirubin must be ≤3.0 mg/dL), and AST ≤ 2.5 ULN. Exclusion Criteria: In Lymphoma: Disease progression by IWG Working Group Criteria since last therapy Patients with history of CNS involvement Prior autologous (only in lymphoma) or allogeneic stem cell transplantation Patients who have failed bendamustine-based regimen previously Patients within 6 months of MI and stroke will be excluded
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Parastoo Dahi, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

Links:
URL
https://www.mskcc.org/
Description
Memorial Sloan Kettering Cancer Center

Learn more about this trial

A Phase I Study of Bendamustine and Melphalan Conditioning and Autologous Stem Cell Transplantation for Treatment of Multiple Myeloma and Relapsed/Refractory B-cell Lymphoma in Elderly Patients

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