NCT01413178 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE3
Status at capture: COMPLETED
Registry last update: 2020-04-21

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Progression-Free Survival (PFS)

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outcome · POSTED

Number of Participants With Complete Response (CR)

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outcome · POSTED

Treatment-Related Mortality (TRM) Between 2 Arms.

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outcome · POSTED

Number of Participants That Had Grade 3-4 Toxicities.

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outcome · POSTED

Overall Survival (OS)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: 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.
healthy Volunteers: false
maximum Age: 70 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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.
intervention Names
Drug: Busulfan
Drug: Melphalan
Other: Questionnaire
Drug: G-CSF
Procedure: Stem cell transplant
label
Busulfan + Melphalan
type
EXPERIMENTAL
description
High-dose Melphalan 200 mg/m2/day IV over 30 minutes on day -2. SCT Day 0.
intervention Names
Other: Questionnaire
Drug: G-CSF
Drug: High Dose Melphalan
Procedure: Stem cell transplant
label
Melphalan
type
EXPERIMENTAL

interventions

arm Group Labels
Busulfan + Melphalan
description
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.
name
Busulfan
other Names
Busulfex
Myleran
type
DRUG
arm Group Labels
Busulfan + Melphalan
description
70 mg/m2 by vein over 30 minutes minutes on Days -2 and -1.
name
Melphalan
other Names
Alkeran
type
DRUG
arm Group Labels
Busulfan + Melphalan
Melphalan
description
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.
name
Questionnaire
other Names
Survey
type
OTHER
arm Group Labels
Busulfan + Melphalan
Melphalan
description
Approximately 5 mcg/kg/day subcutaneously beginning on Day +5.
name
G-CSF
other Names
Filgrastim
NeupogenTM
type
DRUG
arm Group Labels
Melphalan
description
200 mg/m2 by vein over 30 minutes on Day -2.
name
High Dose Melphalan
other Names
Alkeran
type
DRUG
arm Group Labels
Busulfan + Melphalan
Melphalan
description
Stem cell infusion on Day 0.
name
Stem cell transplant
other Names
ABMT
autologous bone marrow transplantation
Peripheral Blood Progenitor Cells
PBPCs
type
PROCEDURE

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 205
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Participants that are still alive and without Multiple Myeloma 3 years after Stem cell Transplantation.
measure
Progression-Free Survival (PFS)
time Frame
3 years after transplant

secondary Outcomes

description
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.
measure
Number of Participants With Complete Response (CR)
time Frame
Evaluated 90 days from transplant.
measure
Treatment-Related Mortality (TRM) Between 2 Arms.
time Frame
100 days post treatment
measure
Number of Participants That Had Grade 3-4 Toxicities.
time Frame
At day 90 post SCT (Stem Cell Transplantation)
measure
Overall Survival (OS)
time Frame
From time of ASCT to 3 years

Full study description

brief Summary: 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.
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.

Source references

references

citation
Bashir Q, Thall PF, Milton DR, Fox PS, Kawedia JD, Kebriaei P, Shah N, Patel K, Andersson BS, Nieto YL, Valdez BC, Parmar S, Rondon G, Delgado R, Hosing C, Popat UR, Oran B, Ciurea SO, Lin P, Weber DM, Thomas SK, Lee HC, Manasanch EE, Orlowski RZ, Williams LA, Champlin RE, Qazilbash MH. Conditioning with busulfan plus melphalan versus melphalan alone before autologous haemopoietic cell transplantation for multiple myeloma: an open-label, randomised, phase 3 trial. Lancet Haematol. 2019 May;6(5):e266-e275. doi: 10.1016/S2352-3026(19)30023-7. Epub 2019 Mar 22.
pmid
30910541
type
DERIVED