Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III	Treatment	Active	18 to 70	NCI, Pharmaceutical / Industry	FHCRC-2004.00 6004, MEDIMMUNE-FHCRC-2004.00, NCT00217438

Objectives

Primary

1. Compare the complete response (CR) and near-CR rates in patients with stage II or III multiple myeloma treated with induction therapy comprising two different doses of high-dose melphalan and amifostine followed by a single autologous or syngeneic peripheral blood stem cell transplantation (PBSCT).

Secondary

1. Compare the toxic effects of these regimens in these patients.
2. Determine the CR and near-CR rates in patients who fail to achieve a CR or near-CR after a single autologous or syngeneic PBSCT and subsequently receive a second course of induction therapy comprising high-dose melphalan and amifostine followed by a second autologous or syngeneic PBSCT.
3. Compare the time to progression in patients treated with these regimens followed by maintenance therapy comprising clarithromycin, thalidomide, and dexamethasone.

Entry Criteria

Disease Characteristics:

• Diagnosis of multiple myeloma (MM)
  • Stage II or III disease
• Planning to undergo autologous or syngeneic peripheral blood stem cell transplantation (PBSCT) for MM
  • Patients undergoing autologous PBSCT must have sufficient stem cells available (i.e., ≥ 3.0 x 10⁶ CD34-positive cells/kg) for 2 transplantations
• Patients who have achieved a complete response or near-complete response after prior conventional therapy are not eligible
• Ineligible for or refused allogeneic stem cell transplantation
• No nonsecretory MM

Prior/Concurrent Therapy:

Biologic therapy

• Prior combination therapy comprising clarithromycin, thalidomide, and a steroid allowed provided the patient achieved a response
• No prior autologous stem cell transplantation
• No concurrent tandem autologous or reduced-intensity allogeneic PBSCT

Chemotherapy

• Not specified

Endocrine therapy

• See Biologic therapy

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age

• 18 to 70

Performance status

• Karnofsky 80-100%

Life expectancy

• Not severely limited by concurrent illness

Hematopoietic

• Not specified

Hepatic

• SGPT < 4 times normal
• Bilirubin < 2 mg/dL

Renal

• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• LVEF ≥ 50%
• No uncontrolled arrhythmia
• No symptomatic cardiac disease

Pulmonary

• FEV₁ ≥ 50%
• Forced vital capacity ≥ 50%
• DLCO ≥ 50%
• No symptomatic pulmonary disease

Immunologic

• HIV negative
• No uncontrolled infection
• No allergy to clarithromycin, thalidomide, or dexamethasone

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile female patients must use effective double-method contraception (1 highly effective and 1 additional method) 4 weeks before, during, and for 4 weeks after completion of study treatment
• Fertile male patients must use effective barrier-method contraception during and for 4 weeks after completion of study treatment
• No sperm, ovum, or blood donation during study treatment
• No history of seizures
• No other illness that would severely limit life expectancy

Expected Enrollment

A total of 130 patients will be accrued for this study.

Outcomes

Compare complete response and near complete response rate after completion of the first transplant

Outline

This is a randomized, controlled, multicenter study. Patients are stratified according to pre-transplantation response (< a partial response [PR] vs > a PR), pre-transplantation serum beta-2 microglobulin level (< 5 mg/dL vs > 5 mg/dL), and the presence of deletion on chromosome 13 by fluorescence in situ hybridization (yes vs no).

• Induction therapy: Patients are randomized to 1 of 2 treatment arms.
  • Arm I (high-dose melphalan and amifostine): 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.
  • Arm II (higher-dose melphalan and amifostine): Patients receive amifostine as in arm I and melphalan as in arm I but at a higher dose.

• Autologous or syngeneic peripheral blood stem cell transplantation (PBSCT): At least 20 hours after completion of melphalan, all 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 complete response (CR) or near-CR proceed to maintenance therapy. Patients who do not achieve a CR or near-CR 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 proceed to maintenance therapy.

• Maintenance therapy: Beginning 90-120 days after first or second PBSCT, patients receive oral clarithromycin twice daily and oral thalidomide once daily for 1 year. Patients also receive oral dexamethasone once weekly for 1 year followed by a taper for 8 weeks. Treatment with thalidomide alone then continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

William Bensinger, MD, Principal investigator		Ph: 206-667-4933

U.S.A.
California
	Los Angeles
	Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center
		Michael Lill, MD	Ph:  310-423-2997
			Email: lillm@cshs.org
New York
	New York
	St. Vincent's Comprehensive Cancer Center - Manhattan
		Sundar Jagannath, MD	Ph:  888-442-2623
			Email: sjaganna@salick.com
	Rochester
	James P. Wilmot Cancer Center at University of Rochester Medical Center
		Gordon Phillips, MD	Ph:  585-273-4399
Washington
	Seattle
	Fred Hutchinson Cancer Research Center
		Kathy Lilleby	Ph:  206-667-5836
	Veterans Affairs Medical Center - Seattle
		Thomas R. Chauncey, MD, PhD	Ph:  206-764-2709 800-329-8387

Registry Information
Official Title		A Multi-center Phase III Study of Autologous Transplantation for Patients with Multiple Myeloma Comparing Melphalan 280 mg/m2 + Amifostine with Melphalan 200mg/m2 + Amifostine
Trial Start Date		2005-07-06
Trial Completion Date		2011-12-01 (estimated)
Registered in ClinicalTrials.gov		NCT00217438
Date Submitted to PDQ		2005-07-19
Information Last Verified		2009-07-05
NCI Grant/Contract Number		CA15704

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