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

NCT03352765 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 17-373
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

Rituximab; Bendamustine; Melphalan; Autologous Stem Cell Transplantation (ASCT); 17-373

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

rituximab, bendamustine & melphalan and ASCT

EXPERIMENTAL

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; Drug: bendamustine; Drug: melphalan; Procedure: Autologous Stem Cell Transplantation (ASCT)

Interventions

rituximab DRUG

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.

rituximab, bendamustine & melphalan and ASCT

bendamustine DRUG

bendamustine 160 mg/m2 intravenously on days -3 and -2

rituximab, bendamustine & melphalan and ASCT

melphalan DRUG

melphalan 140 mg/m2 intravenously on day -1 before the reinfusion of autologous stem cells on day 0.

rituximab, bendamustine & melphalan and ASCT

Autologous Stem Cell Transplantation (ASCT) PROCEDURE

reinfusion of autologous stem cells on day 0.

rituximab, bendamustine & melphalan and ASCT

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma

Interventions

Rituximab; Bendamustine Hydrochloride; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids

Study Officials

• Parastoo Dahi, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase I single arm, open label trial

Study Record Dates

• First Submitted: November 21, 2017
• First Posted: November 24, 2017
• Study Start: November 20, 2017
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 4, 2025

Record last verified: 2025-12

Locations

US (1)