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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03352765

Collaborator

(none)

Enrollment

Location

Arm

71.4

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a phase I single arm, open label trialThis 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 :

Nov 20, 2017

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 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.

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

Dose limiting toxicities (DLT) [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

Criteria

Ages Eligible for Study:

65 Years and Older

Sexes Eligible for Study:

All

Accepts 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