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

Primary Purpose

Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bendamustine
Melphalan
Bendamustine
Bendamustine
Bendamustine
Bendamustine
Bendamustine
Sponsored by
Weill Medical College of Cornell University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring Multiple Myeloma, Autologous Stem Cell Transplant, ASCT, MM

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Sites / Locations

  • Weill Cornell Medical College

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose Level 1

Dose Level 2

Dose Level 3

Dose Level 4

Dose Level 5

Dose Level 6

Phase 2

Arm Description

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)

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)

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)

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)

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)

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)

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)

Outcomes

Primary Outcome Measures

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.
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

Secondary Outcome Measures

Progression-Free Survival (Phase 1)
Time elapsed between Day 0 and disease progression, as defined by the International Myeloma Working Group (IMWG) disease response criteria. Disease progression is defined as an increase of >25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL) Urine M-component and/or (the absolute increase must be > 200 mg/24 h) Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved free light chain levels. The absolute increase must be > 10 mg/dL Bone marrow plasma cell percentage; the absolute percentage must be > 10% Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder
Progression-Free Survival (Phase 2)
Time elapsed between Day 0 and disease progression, as defined by the International Myeloma Working Group (IMWG) disease response criteria. Disease progression is defined as an increase of >25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL) Urine M-component and/or (the absolute increase must be > 200 mg/24 h) Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved free light chain levels. The absolute increase must be > 10 mg/dL Bone marrow plasma cell percentage; the absolute percentage must be > 10% Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder
Overall Survival at 2 Years (Phase 1)
Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 2 years.
Overall Survival at 3 Years (Phase 2)
Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 3 years.

Full Information

First Posted
June 5, 2009
Last Updated
May 14, 2019
Sponsor
Weill Medical College of Cornell University
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1. Study Identification

Unique Protocol Identification Number
NCT00916058
Brief Title
Conditioning Regimen of Bendamustine and Melphalan Followed by Transplant in Patients With Multiple Myeloma
Official Title
A Phase 1-2 Study of a Novel Conditioning Regimen of Bendamustine and Melphalan Followed by Autologous Stem Cell Transplant for Patients With Multiple Myeloma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
April 23, 2009 (Actual)
Primary Completion Date
March 11, 2016 (Actual)
Study Completion Date
March 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Weill Medical College of Cornell University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
Bendamustine (TREANDA™) has been used in clinical trials to treat multiple myeloma. The results from these trials suggest that it may be beneficial in the treatment of multiple myeloma in a different treatment context. Researchers aim to determine if there may be an improved benefit in the context of bone marrow transplant. This initial clinical trial is intended to help determine how safe it is to use bendamustine as a conditioning regimen for bone marrow transplant, and to look for any initial evidence of benefit. Bendamustine (TREANDA™) is approved by the Food and Drug Administration (FDA) for the treatment of Chronic Lymphocytic Leukemia and Melphalan is a type of chemotherapy drug. The use of Melphalan alone as a conditioning regimen for Autologous Stem Cell Transplant is considered "Standard of Care," that is, the treatment or process that your doctor would normally follow to treat your disease. Although Bendamustine (TREANDA™) has been used in multiple myeloma research studies, the combination of Bendamustine (TREANDA™) and Melphalan as treatment for Multiple Myeloma is not approved by the FDA, thus the combination therapy used in this research study is considered "investigational."

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Multiple Myeloma, Autologous Stem Cell Transplant, ASCT, MM

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Level 1
Arm Type
Experimental
Arm Description
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)
Arm Title
Dose Level 2
Arm Type
Experimental
Arm Description
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)
Arm Title
Dose Level 3
Arm Type
Experimental
Arm Description
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)
Arm Title
Dose Level 4
Arm Type
Experimental
Arm Description
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)
Arm Title
Dose Level 5
Arm Type
Experimental
Arm Description
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)
Arm Title
Dose Level 6
Arm Type
Experimental
Arm Description
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)
Arm Title
Phase 2
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
30 mg/m^2 given on day 2 of melphalan
Intervention Type
Drug
Intervention Name(s)
Melphalan
Other Intervention Name(s)
Alkeran
Intervention Description
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
60 mg/m^2 given on the 2nd day of melphalan
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
90 mg/m^2 given on the 2nd day of melphalan
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
60 mg/m^2 given on the 1st and 2nd day of melphalan
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Other Intervention Name(s)
Treanda
Intervention Description
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Primary Outcome Measure Information:
Title
Maximum Tolerated Dose (Phase 1)
Description
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.
Time Frame
35 days post-transplant
Title
Overall Response Rate (Phase 2) - Number of Participants Achieving at Least a Partial Response or Better in Disease Status at Day 100 Post-transplant
Description
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
Time Frame
100 days post-transplant
Secondary Outcome Measure Information:
Title
Progression-Free Survival (Phase 1)
Description
Time elapsed between Day 0 and disease progression, as defined by the International Myeloma Working Group (IMWG) disease response criteria. Disease progression is defined as an increase of >25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL) Urine M-component and/or (the absolute increase must be > 200 mg/24 h) Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved free light chain levels. The absolute increase must be > 10 mg/dL Bone marrow plasma cell percentage; the absolute percentage must be > 10% Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder
Time Frame
From Day 0 to first incidence of disease progression, up to 1,128 days
Title
Progression-Free Survival (Phase 2)
Description
Time elapsed between Day 0 and disease progression, as defined by the International Myeloma Working Group (IMWG) disease response criteria. Disease progression is defined as an increase of >25% from lowest response value in any one or more of the following: Serum M-component and/or (the absolute increase must be > 0.5 g/dL) Urine M-component and/or (the absolute increase must be > 200 mg/24 h) Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved free light chain levels. The absolute increase must be > 10 mg/dL Bone marrow plasma cell percentage; the absolute percentage must be > 10% Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder
Time Frame
From Day 0 to first incidence of disease progression, up to 86 months
Title
Overall Survival at 2 Years (Phase 1)
Description
Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 2 years.
Time Frame
From Day 0 until time of death, assessed up to 2 years.
Title
Overall Survival at 3 Years (Phase 2)
Description
Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 3 years.
Time Frame
From Day 0 until time of death, assessed up to 3 years.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tsiporah Shore, M.D.
Organizational Affiliation
Weill Medical College of Cornell University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31190006
Citation
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.
Results Reference
derived

Learn more about this trial

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

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