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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma
• Intervention / Treatment: Drug: rituximab; Drug: bendamustine; Drug: melphalan; Procedure: Autologous Stem Cell Transplantation (ASCT)

• Study Type: Interventional
• Enrollment (Estimated): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: rituximab, bendamustine & melphalan and ASCT; 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.

Drug: rituximab; 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.; Drug: bendamustine; bendamustine 160 mg/m2 intravenously on days -3 and -2; Drug: melphalan; melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0.; Procedure: Autologous Stem Cell Transplantation (ASCT); reinfusion of autologous stem cells on day 0.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	1 year

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Parastoo Dahi, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2017
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (Actual): November 24, 2017

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: December 2, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Rituximab; Bendamustine; Melphalan; Autologous Stem Cell Transplantation (ASCT); 17-373
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemic and Lymphatic Diseases; Lymphoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hydrocarbons; Acids, Acyclic; Carboxylic Acids; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Amino Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Butyrates; Antibodies, Monoclonal, Murine-Derived; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Bendamustine Hydrochloride; Rituximab; Melphalan
• Other Study ID Numbers: 17-373

Drug and device information, study documents

• 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