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

May 14, 2019 updated by: Weill Medical College of Cornell University

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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."

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
57

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • Weill Cornell Medical College

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dose Level 1
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
30 mg/m^2 given on day 2 of melphalan
Other Names:
  • Treanda
Drug: Melphalan
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
  • Alkeran
Drug: Bendamustine
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Experimental: Dose Level 2
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: Bendamustine
30 mg/m^2 given on day 2 of melphalan
Other Names:
  • Treanda
Drug: Melphalan
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
  • Alkeran
Drug: Bendamustine
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Experimental: Dose Level 3
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: Bendamustine
30 mg/m^2 given on day 2 of melphalan
Other Names:
  • Treanda
Drug: Melphalan
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
  • Alkeran
Drug: Bendamustine
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Experimental: Dose Level 4
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: Bendamustine
30 mg/m^2 given on day 2 of melphalan
Other Names:
  • Treanda
Drug: Melphalan
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
  • Alkeran
Drug: Bendamustine
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Experimental: Dose Level 5
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: Bendamustine
30 mg/m^2 given on day 2 of melphalan
Other Names:
  • Treanda
Drug: Melphalan
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
  • Alkeran
Drug: Bendamustine
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Experimental: Dose Level 6
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: Bendamustine
30 mg/m^2 given on day 2 of melphalan
Other Names:
  • Treanda
Drug: Melphalan
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
  • Alkeran
Drug: Bendamustine
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Experimental: Phase 2
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: Bendamustine
30 mg/m^2 given on day 2 of melphalan
Other Names:
  • Treanda
Drug: Melphalan
100 mg/m^2 for 2 days (70 mg/m^2 for patients with Creatinine Clearance <70 ml/min)
Other Names:
  • Alkeran
Drug: Bendamustine
60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
60 mg/m^2 given on the 1st and 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
90 mg/m^2 given on the 1st day of melphalan and 60 mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda
Drug: Bendamustine
125 mg/m^2 given on the 1st day of melphalan and 100mg/m^2 given on the 2nd day of melphalan
Other Names:
  • Treanda

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (Phase 1)
Time Frame: 35 days post-transplant
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
Time Frame: 100 days 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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (Phase 1)
Time Frame: From Day 0 to first incidence of disease progression, up to 1,128 days

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
From Day 0 to first incidence of disease progression, up to 1,128 days
Progression-Free Survival (Phase 2)
Time Frame: From Day 0 to first incidence of disease progression, up to 86 months

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
From Day 0 to first incidence of disease progression, up to 86 months
Overall Survival at 2 Years (Phase 1)
Time Frame: From Day 0 until time of death, assessed up to 2 years.
Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 2 years.
From Day 0 until time of death, assessed up to 2 years.
Overall Survival at 3 Years (Phase 2)
Time Frame: From Day 0 until time of death, assessed up to 3 years.
Time elapsed between Day 0 and death from any cause, whichever came first, assessed up to 3 years.
From Day 0 until time of death, assessed up to 3 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Weill Medical College of Cornell University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Tsiporah Shore, M.D., Weill Medical College of Cornell University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 23, 2009

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 11, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 5, 2009

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 8, 2009

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 9, 2009

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 4, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 14, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 0812010147

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