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 - Full Text View

Sponsor:	Fred Hutchinson Cancer Research Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:	NCT00217438

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 III

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:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

Drug Information available for: Amifostine Melphalan Sarcolysin Melphalan hydrochloride

U.S. FDA Resources

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

Primary Outcome Measures:

CR and near CR rates [ Time Frame: After transplant #1 ] [ 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: During treatment and after completion of the first transplant ] [ Designated as safety issue: No ]

Estimated Enrollment:	130
Study Start Date:	July 2005
Estimated Primary Completion Date:	July 2015 (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

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

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

Locations

United States, California
Cedars-Sinai Medical Center	Recruiting
Los Angeles, California, United States, 90048
Contact: Michael Charles C. Lill 310-423-2997
Principal Investigator: Michael Charles C. Lill
United States, New York
University of Rochester	Recruiting
Rochester, New York, United States, 14642
Contact: Gordon L. Phillips 585-273-4399
Principal Investigator: Gordon L. Phillips
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Recruiting
Seattle, Washington, United States, 98109
Contact: William I. Bensinger 206-667-4933
Principal Investigator: William I. Bensinger
VA Puget Sound Health Care System	Recruiting
Seattle, Washington, United States, 98101
Contact: Thomas R. Chauncey 206-764-2709
Principal Investigator: Thomas R. Chauncey

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

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 28, 2011
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
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012