Conditioning Regimen of Bendamustine and Melphalan Followed by Transplant in Patients With Multiple Myeloma

NCT00916058 | Completed Phase 1 Results DMC

• 1 other identifier: 0812010147
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of Bendamustine (TREANDA™), in combination with Melphalan in subjects with multiple myeloma who are undergoing an Autologous Stem Cell Transplant.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Autologous Stem Cell Transplant; ASCT; MM

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose (Phase 1)

  The Maximum Tolerated Dose was not met in Phase 1 of the study. Phase 2 participants were enrolled at the highest dose administered in Phase 1 (Dose Level 6) and this Outcome Measure is the reported number of dose-limiting toxicities experienced by Phase 1 participants. DLTs were defined as any grade 3 non-hematologic adverse even that did not resolve within 72 hours, any occurrence of a grade 4 non-hematologic adverse event, or failure to engraft with an absolute neutrophil count of 500/mm\^3 and platelet count of 20,000/mm\^3 untransfused by Day 35 post-transplant.

  35 days post-transplant

• Overall Response Rate (Phase 2) - Number of Participants Achieving at Least a Partial Response or Better in Disease Status at Day 100 Post-transplant

  Number of patients achieving at least a partial response or better in disease status at Day 100 post-transplant, as defined by the International Myeloma Working Group (IMWG) disease response criteria. Partial response in disease status is defined by the IMWG as ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to \<200 mg per 24 hours; If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria; If serum and urine M-protein are unmeasurable, and serum-free light assay is also unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma-cell percentage was ≥30%. In addition to these criteria, if present at baseline, a ≥50% reduction in the size (SPD) of soft tissue plasmacytomas is also required

  100 days post-transplant

Secondary Outcomes (4)

• Progression-Free Survival (Phase 1)

  From Day 0 to first incidence of disease progression, up to 1,128 days

• Progression-Free Survival (Phase 2)

  From Day 0 to first incidence of disease progression, up to 86 months

• Overall Survival at 2 Years (Phase 1)

  From Day 0 until time of death, assessed up to 2 years.

• Overall Survival at 3 Years (Phase 2)

  From Day 0 until time of death, assessed up to 3 years.

Study Arms (7)

Dose Level 1

EXPERIMENTAL

Dose Level 1; Bendamustine 30 mg/m\^2 total, Melphalan 200 mg/m\^2 total (140 mg/m\^2 total for patients with Creatinine Clearance \<70 ml/min)

Drug: Bendamustine; Drug: Melphalan

Dose Level 2

EXPERIMENTAL

Dose Level 2; Bendamustine 60 mg/m\^2 total, Melphalan 200 mg/m\^2 total (140 mg/m\^2 total for patients with Creatinine Clearance \<70 ml/min)

Drug: Melphalan; Drug: Bendamustine

Dose Level 3

EXPERIMENTAL

Dose Level 3; Bendamustine 90 mg/m\^2 total, Melphalan 200 mg/m\^2 total (140 mg/m\^2 total for patients with Creatinine Clearance \<70 ml/min)

Drug: Melphalan; Drug: Bendamustine

Dose Level 4

EXPERIMENTAL

Dose Level 4; Bendamustine 120 mg/m\^2 total, Melphalan 200 mg/m\^2 total (140 mg/m\^2 total for patients with Creatinine Clearance \<70 ml/min)

Drug: Melphalan; Drug: Bendamustine

Dose Level 5

EXPERIMENTAL

Dose Level 5; Bendamustine 150 mg/m\^2 total, Melphalan 200 mg/m\^2 total (140 mg/m\^2 total for patients with Creatinine Clearance \<70 ml/min)

Drug: Melphalan; Drug: Bendamustine

Dose Level 6

EXPERIMENTAL

Dose Level 6; Bendamustine 225 mg/m\^2 total, Melphalan 200 mg/m\^2 total (140 mg/m\^2 total for patients with Creatinine Clearance \<70 ml/min)

Drug: Melphalan; Drug: Bendamustine

Phase 2

EXPERIMENTAL

Bendamustine 225 mg/m\^2 total, Melphalan 200 mg/m\^2 total (140 mg/m\^2 total for patients with Creatinine Clearance \<70 ml/min)

Drug: Melphalan; Drug: Bendamustine

Interventions

Bendamustine DRUG

30 mg/m\^2 given on day 2 of melphalan

Also known as: Treanda

Dose Level 1

Melphalan DRUG

100 mg/m\^2 for 2 days (70 mg/m\^2 for patients with Creatinine Clearance \<70 ml/min)

Also known as: Alkeran

Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4; Dose Level 5; Dose Level 6; Phase 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with multiple myeloma who have received induction therapy and have had stem cells mobilized in preparation for autologous transplantation will be eligible for this study. Patients are also eligible with relapsed or refractory disease, after attempts at more standard approaches, and with the availability of stem cells.
• Patients must be age 18 or older.
• Patients must have a life expectancy of at least 12 weeks.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.
• Patients must provide written informed consent.

You may not qualify if:

• Impaired renal function with a measured or calculated creatinine clearance of less than 25 ml/min.
• Impaired hepatic function defined as a bilirubin greater than 1.5 x upper limit of normal (ULN) or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 5 x ULN.
• Serious active or uncontrolled infection or medical condition.
• Women who are pregnant or breast feeding. Women of childbearing age must use adequate contraception and have a negative pregnancy test.
• Impaired pulmonary function with a diffusing capacity of the lung for carbon monoxide (DLCO) less than 45% predicted.
• Impaired cardiac function with an ejection fraction less than 40% of predicted.
• Other systemic anticancer therapy or ongoing toxicities from such therapy.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead

Study Sites (1)

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Related Publications (1)

• Gomez-Arteaga A, Mark TM, Guarneri D, Christos PJ, Gergis U, Greenberg JD, Hsu J, Mayer SA, Niesvizky R, Pearse RN, Phillips AA, Rossi A, Coleman M, van Besien K, Shore TB. High-dose bendamustine and melphalan conditioning for autologous stem cell transplantation for patients with multiple myeloma. Bone Marrow Transplant. 2019 Dec;54(12):2027-2038. doi: 10.1038/s41409-019-0587-0. Epub 2019 Jun 12.

  PMID: 31190006 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bendamustine Hydrochloride; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

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; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Tsiporah Shore
• Organization: Weill Cornell Medical College

tbs2001@med.cornell.edu

646-962-7950

Study Officials

• Tsiporah Shore, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 5, 2009
• First Posted: June 9, 2009
• Study Start: April 23, 2009
• Primary Completion: March 11, 2016
• Study Completion: March 1, 2018
• Last Updated: June 4, 2019
• Results First Posted: June 4, 2019

Record last verified: 2019-05

Locations

US (1)