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

• ClinicalTrials.gov Identifier: NCT03352765
• Recruitment Status: Recruiting
• First Posted: November 24, 2017
• Last Update Posted: March 8, 2022
• Sponsor: Memorial Sloan Kettering Cancer Center
• Information provided by (Responsible Party): Memorial Sloan Kettering Cancer Center

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.

Condition or disease	Intervention/treatment	Phase
Lymphoma	Drug: rituximab; Drug: bendamustine; Drug: melphalan; Procedure: Autologous Stem Cell Transplantation (ASCT)	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: This is a phase I single arm, open label trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: November 20, 2017
• Estimated Primary Completion Date: November 2023
• Estimated Study Completion Date: November 2023

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Dose limiting toxicities (DLT) [ Time Frame: 1 year ]
   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

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Parastoo Dahi, MD; 212-639-5846; ABMTTrials@mskcc.org

Contact: Paul Hamlin, MD; 908-542-3366; ABMTTrials@mskcc.org

Locations

United States, New York

Memorial Sloan Kettering Cancer Center; Recruiting

New York, New York, United States, 10065

Contact: Parastoo Dahi, MD 212-639-5846

Contact: Paul Hamlin, MD 908-542-3366

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

Investigators

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

More Information

Additional Information:

Memorial Sloan Kettering Cancer Center 

• Responsible Party: Memorial Sloan Kettering Cancer Center
• ClinicalTrials.gov Identifier: NCT03352765
• Other Study ID Numbers: 17-373
• First Posted: November 24, 2017
• Last Update Posted: March 8, 2022
• Last Verified: March 2022

• 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

Keywords provided by Memorial Sloan Kettering Cancer Center:

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

Additional relevant MeSH terms:

Lymphoma; Multiple Myeloma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Rituximab; Melphalan; Bendamustine Hydrochloride; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Myeloablative Agonists; Immunosuppressive Agents