Melphalan and Amifostine Followed By One or Two Autologous or Syngeneic Stem Cell Transplants and Maintenance Therapy in Treating Patients With Stage II-III Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00217438
First received: September 20, 2005
Last updated: December 26, 2012
Last verified: December 2012
  Purpose

RATIONALE: Giving chemotherapy drugs, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Chemoprotective drugs, such as amifostine, may protect normal cells from the side effects of chemotherapy. Giving chemotherapy with a peripheral stem cell transplant once or twice, using stem cells from the patient or an identical brother or sister, may allow more chemotherapy to be given so more cancer cells are killed. Giving maintenance therapy after a stem cell transplant may kill any cancer cells that remain. It is not yet known which dose of melphalan is more effective in treating multiple myeloma (MM).

PURPOSE: This randomized phase III trial is studying two different doses of melphalan to compare how well they work when given together with amifostine followed by one or two autologous or syngeneic stem cell transplants and maintenance therapy in treating patients with stage II-III MM


Condition Intervention Phase
Refractory Multiple Myeloma
Stage II Multiple Myeloma
Stage III Multiple Myeloma
Drug: melphalan
Drug: amifostine trihydrate
Procedure: peripheral blood stem cell transplantation
Genetic: fluorescence in situ hybridization
Procedure: bone marrow ablation with stem cell support
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multi-Center Phase III Study of Autologous Transplantation for Patients With Multiple Myeloma Comparing Melphalan 280 mg/m2 + Amifostine With Melphalan 200 mg/m2 + Amifostine

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • CR and near CR rates [ Time Frame: Up to 120 days after transplant ] [ Designated as safety issue: No ]
    Observe a statistically significant difference at the two-sided significance level of .05 with 80% and 90% power for various assumed-true CR rates.


Secondary Outcome Measures:
  • Relative toxicities between melphalan 280 mg/m^2 or melphalan 200 mg/m^2 [ Time Frame: Up to day 56 after transplant ] [ Designated as safety issue: No ]

Enrollment: 130
Study Start Date: July 2005
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (high dose melphalan, amifostine trihydrate, transplant)

INDUCTION THERAPY:

Patients receive amifostine IV over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day 2.

AUTOLOGOUS OR SYNGENEIC PBSCT: At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy.

Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Drug: amifostine trihydrate
Given IV
Other Names:
  • ethiofos
  • Ethyol
  • gammaphos
  • WR-2721
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Genetic: fluorescence in situ hybridization
Correlative study
Other Name: fluorescence in situ hybridization (FISH)
Procedure: bone marrow ablation with stem cell support
Undergo transplant
Active Comparator: Arm II (low dose melphalan, amifostine trihydrate, transplant)

INDUCTION THERAPY:

Patients receive amifostine as in arm I and melphalan as in arm I at a lower dose.

AUTOLOGOUS OR SYNGENEIC PBSCT: At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy.

Drug: melphalan
Given IV
Other Names:
  • Alkeran
  • CB-3025
  • L-PAM
  • L-phenylalanine mustard
  • L-Sarcolysin
Drug: amifostine trihydrate
Given IV
Other Names:
  • ethiofos
  • Ethyol
  • gammaphos
  • WR-2721
Procedure: peripheral blood stem cell transplantation
Undergo PBSCT
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Genetic: fluorescence in situ hybridization
Correlative study
Other Name: fluorescence in situ hybridization (FISH)
Procedure: bone marrow ablation with stem cell support
Undergo transplant

Detailed Description:

PRIMARY OBJECTIVES:

I. Compare the complete response (CR) and near CR rate in patients undergoing autologous stem cell transplant (ASCT) using melphalan 280 mg/m^2 or melphalan 200 mg/m^2.

SECONDARY OBJECTIVES:

I. Compare toxicities between patients receiving amifostine and melphalan 280 mg/m^2 or melphalan 200 mg/m^2.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

INDUCTION THERAPY:

ARM I (HIGH DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine intravenously (IV) over 3-5 minutes on days -3 and -2 followed by high-dose melphalan IV over 15-30 minutes on day 2.

ARM II (LOW DOSE MELPHALAN AND AMIFOSTINE): Patients receive amifostine as in arm I and melphalan as in arm I at a lower dose.

AUTOLOGOUS OR SYNGENEIC PERIPHERAL BLOOD STEM CELL TRANSPLANTATION (PBSCT): At least 20 hours after completion of melphalan, patients undergo autologous or syngeneic PBSCT on day 0.

Patients undergo restaging of the disease between days 80-90. Patients with progressive disease are removed from the study. Patients who achieve a CR or near-CR can proceed to optional maintenance therapy. Patients who do not achieve a CR or near-CR may undergo additional induction therapy as in arm I followed by a second autologous or syngeneic PBSCT.

Patients again undergo restaging of the disease 80-90 days later. Patients with progressive disease are removed from the study. Patients without progressive disease can proceed to maintenance therapy.

After completion of study treatment, patients are followed up every 3 months for 5 years.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients who have MM undergoing autologous or syngeneic hematopoietic transplantation
  • Patients must meet Salmon and Durie criteria for initial diagnosis of MM
  • Transplant will be offered to patients with stage II or III MM
  • Measurable disease, defined as serum monoclonal protein >= 0.2 g/dl or Bence Jones protein >= 200 mg/24 h
  • Karnofsky >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2
  • Life expectancy is not severely limited by concomitant illness
  • Left ventricular ejection fraction >= 50%
  • No uncontrolled arrhythmias or symptomatic cardiac disease
  • Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusion capacity of carbon monoxide (DLCO) >= 50%
  • No symptomatic pulmonary disease
  • Human immunodeficiency virus (HIV) negative
  • Bilirubin < 2 mg/dl
  • Serum glutamic pyruvate transaminase (SGPT) < 2.5 x normal
  • Creatinine clearance >= 60 cc/min, estimated or measured
  • Signed informed consent

Exclusion Criteria:

  • Pregnant or lactating females
  • Uncontrolled infection
  • Planned tandem autologous/reduced intensity allograft
  • Insufficient PBSC for an autologous transplant (< 3.0 x 10^6 CD34+ cells/kg total)
  • Prior autologous transplant
  • Non-secretory myeloma and patients who are in a complete response or near complete response after conventional therapy
  • Patients unwilling to practice adequate forms of contraception if clinically indicated
  • Male patients on study need to be consulted to use latex condoms, even if they have had a vasectomy, every time they have sex with a woman who is able to have children
  • Patients with history of seizures
  • Patients receiving antihypertensive therapy that cannot be stopped for 24 hours preceding amifostine treatment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00217438

Locations
United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, New York
University of Rochester
Rochester, New York, United States, 14642
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
VA Puget Sound Health Care System
Seattle, Washington, United States, 98101
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Investigators
Principal Investigator: William Bensinger Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Bensinger, William, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT00217438     History of Changes
Other Study ID Numbers: 2004.00, NCI-2009-01543
Study First Received: September 20, 2005
Last Updated: December 26, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Amifostine
Melphalan
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 01, 2014