A Randomized Trial to Compare Busulfan + Melphalan 140 mg/m2 With Melphalan 200 mg/m2 as Preparative Regimen for Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

April 7, 2020 updated by: M.D. Anderson Cancer Center

The goal of this clinical research study is to compare Busulfex (busulfan) with or without Alkeran (melphalan) to learn which study therapy may be better at helping to control MM in patients who will receive an autologous stem cell transplant. The safety of this combination therapy will also be studied.

Melphalan and busulfan are designed to damage the DNA (genetic material) of cells, which may cause cancer cells to die.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 study groups.

  • Group 1 will receive melphalan and busulfan.
  • Group 2 will receive melphalan.

Both groups will have a stem cell transplant.

Study Drug Administration:

If you are in Group 1, you will first receive an additional low-level "test" dose of busulfan given by vein to check how your blood levels change over time. This information will be used to decide the next dose that is needed to reach a target blood level of busulfan. Blood (about 1 teaspoon each time) will be drawn up to 11 times during the next 11 hours after the test dose and the first high-dose busulfan treatment.

A heparin lock line will be placed in a vein to lower the number of needle sticks needed for these draws.

This test dose of busulfan can be given as an outpatient before you are admitted to the hospital, or you will be admitted on Day -10 (10 days before your transplant) and will receive the test dose on Day -9. If it is not possible for these blood level tests to be performed for technical or scheduling reasons, you will receive the standard, fixed (unchanging) dose of busulfan.

Eight (8) or 10 days before the transplant, you will be admitted to the hospital and given hydration fluids by vein.

On Days -7, -6, -5, and -4, you will receive busulfan by vein over 3 hours. You will receive melphalan on Days -2 and -1 by vein over 30 minutes. You will receive the stem cell transplant through the CVC on Day 0.

If you are in Group 2, you may be admitted to the hospital 3 days before the transplant. You will receive hydration fluids by vein. Two (2) days before the transplant, you will receive melphalan by vein over 30 minutes. You will not receive melphalan the day before the transplant.

Stem Cell Transplant:

The day that you receive the stem cell transplant is called Day 0. The stem cells will be given by vein through the CVC. The cells will travel to your bone marrow where they are designed to start making healthy, new blood cells after several weeks. You will sign a separate consent for the collection of your stem cells.

Beginning 5 days after the transplant, you will receive filgrastim (G-CSF) through a needle under your skin 1 time each day until your blood cell levels return to normal. Filgrastim is designed to help with the growth of white blood cells.

You will be in the hospital after the transplant for about 2-4 weeks.

Questionnaire:

You will be asked to complete a quality-of-life questionnaire before starting the study drugs and then once a week during Weeks 1, 2, and 4 after the stem cell transplant. The questionnaire will take about 15 minutes to complete.

Follow-Up Visits:

About 3 months after the transplant, you will have a bone marrow aspiration and biopsy to check the status of the disease. To collect a bone marrow aspiration and biopsy, an area of the hip is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle.

Every 3 months during the first year after the transplant, blood (about 1-2 tablespoons) will be drawn to check your immune response and status of the disease.

About 1 year after the transplant, you will have a bone scan if the doctor thinks it is needed.

Length of Study:

One (1) year after the transplant, your participation in this study will be over.

If intolerable side effects from the chemotherapy occur or there is sign of disease after the transplant, you will be taken off study. If you have intolerable side effects after you receive chemotherapy, then you will still have the transplant. If you are taken off study early, you still may need to return for routine post-transplant follow-up visits, if your transplant doctor decides it is needed.

This is an investigational study. Busulfan and melphalan are commercially available and FDA approved for the treatment of myeloma. The use of melphalan alone before an autologous stem cell transplant is considered standard of care. Using busulfan with melphalan is investigational.

Up to 205 patients will take part in this study. All will be enrolled at MD Anderson.

Study Type

Interventional

Enrollment (Actual)

205

Phase

  • Phase 3

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
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center

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

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients with multiple myeloma in complete remission (CR), partial remission (PR), or very good partial remission (VGPR), or symptomatic stable disease (no evidence of progression) including patients with light chain MM detected in the serum by free light chain assay.
  2. Patients with non-secretory multiple myeloma [absence of a monoclonal protein (M protein) in serum as measured by electrophoresis (SPEP) and immunofixation (SIFE) and the absence of Bence Jones protein in the urine (UPEP) defined by use of conventional electrophoresis and immunofixation (UIFE) techniques] but with measurable disease on imaging studies like MRI, CT scan or PET scan.
  3. Who have received at least two cycles of initial systemic therapy and are within 2 to 12 months of the first dose. Mobilization therapy is not considered initial therapy.
  4. 70 years of age or younger.
  5. Karnofsky performance score 70% or higher.
  6. Cardiac function: left ventricular ejection fraction at rest > 40% within 3 months of registration.
  7. Hepatic function: bilirubin < 2x the upper limit of normal and ALT and AST < 2.5x the upper limit of normal.
  8. Renal function: creatinine clearance of >/= 40 mL/min, estimated or calculated.
  9. Pulmonary function: DLCO, FEV1, FVC >/= 50% of predicted value (corrected for hemoglobin) within 3 months of registration
  10. Signed informed consent form.

Exclusion Criteria:

  1. Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).
  2. Patients seropositive for the human immunodeficiency virus (HIV).
  3. Patients with history of myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
  4. Patients participating in an investigational new drug protocol within 14 days before enrollment.
  5. Female patients who are pregnant (positive b-HCG) or breastfeeding.
  6. Prior stem cell transplantation allogeneic or autologous.
  7. Prior organ transplant requiring immunosuppressive 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: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Busulfan + Melphalan
Busulfan test dose (32 mg/m^2) on day -9 then 130 mg/m^2 intravenous (IV) Days -7, -6, -5, and -4 + Melphalan 70 mg/m2 IV on Days -2 and -1. Stem Cell Transplant (SCT) Day 0.
Drug: Busulfan
Test dose (32 mg/m^2) on day -9 then 130 mg/m^2 by vein or adjusted dose on Days -7, -6, -5, and -4.
Other Names:
  • Busulfex
  • Myleran
Drug: Melphalan
70 mg/m2 by vein over 30 minutes minutes on Days -2 and -1.
Other Names:
  • Alkeran
Other: Questionnaire
Quality of Life (QOL) questionnaire before starting the study drugs and then once every 4 weeks after the stem cell transplant, taking about 15 minutes to complete.
Other Names:
  • Survey
Drug: G-CSF
Approximately 5 mcg/kg/day subcutaneously beginning on Day +5.
Other Names:
  • Filgrastim
  • NeupogenTM
Procedure: Stem cell transplant
Stem cell infusion on Day 0.
Other Names:
  • ABMT
  • autologous bone marrow transplantation
  • Peripheral Blood Progenitor Cells
  • PBPCs
EXPERIMENTAL: Melphalan
High-dose Melphalan 200 mg/m2/day IV over 30 minutes on day -2. SCT Day 0.
Other: Questionnaire
Quality of Life (QOL) questionnaire before starting the study drugs and then once every 4 weeks after the stem cell transplant, taking about 15 minutes to complete.
Other Names:
  • Survey
Drug: G-CSF
Approximately 5 mcg/kg/day subcutaneously beginning on Day +5.
Other Names:
  • Filgrastim
  • NeupogenTM
Procedure: Stem cell transplant
Stem cell infusion on Day 0.
Other Names:
  • ABMT
  • autologous bone marrow transplantation
  • Peripheral Blood Progenitor Cells
  • PBPCs
Drug: High Dose Melphalan
200 mg/m2 by vein over 30 minutes on Day -2.
Other Names:
  • Alkeran

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival (PFS)
Time Frame: 3 years after transplant
Participants that are still alive and without Multiple Myeloma 3 years after Stem cell Transplantation.
3 years after transplant

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Complete Response (CR)
Time Frame: Evaluated 90 days from transplant.
Complete response (CR), evaluated 90 days from transplant, defined as (i) negative immunofixation of the multiple myeloma (MM) protein in urine and serum, (ii) disappearance of any soft tissue plasmacytomas, and (iii) less than 5% plasma MM cells in the bone marrow. International Myeloma Working Group uniform response criteria.
Evaluated 90 days from transplant.
Treatment-Related Mortality (TRM) Between 2 Arms.
Time Frame: 100 days post treatment
100 days post treatment
Number of Participants That Had Grade 3-4 Toxicities.
Time Frame: At day 90 post SCT (Stem Cell Transplantation)
At day 90 post SCT (Stem Cell Transplantation)
Overall Survival (OS)
Time Frame: From time of ASCT to 3 years
From time of ASCT to 3 years

Collaborators and Investigators

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

Sponsor

M.D. Anderson Cancer Center

Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

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

Helpful Links

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)

September 30, 2011

Primary Completion (ACTUAL)

March 10, 2019

Study Completion (ACTUAL)

March 10, 2019

Study Registration Dates

First Submitted

August 8, 2011

First Submitted That Met QC Criteria

August 8, 2011

First Posted (ESTIMATE)

August 10, 2011

Study Record Updates

Last Update Posted (ACTUAL)

April 21, 2020

Last Update Submitted That Met QC Criteria

April 7, 2020

Last Verified

April 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-0071
  • NCI-2011-02760 (REGISTRY: NCI CTRP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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