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
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Drug/Agent Toxicity by Tissue/Organ; Multiple Myeloma and Plasma Cell Neoplasm
Intervention: amifostine trihydrate (Drug); melphalan (Drug)
Phase: Phase 3
Status: Recruiting
Sponsored by: Fred Hutchinson Cancer Research Center Official(s) and/or principal investigator(s):
William I. Bensinger, MD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center
Summary
RATIONALE: Drugs used in chemotherapy, 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.
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 or stage III multiple myeloma.
Clinical Details
Official title: A Multi-Center Phase III Study of Autologous Transplantation for Patients With Multiple Myeloma Comparing Melphalan 280 mg/m + Amifostine With Melphalan 200mg/m + Amifostine
Study design: Treatment, Randomized, Active Control
Primary outcome: Compare complete response and near complete response rate after completion of the first transplant
Detailed description:
OBJECTIVES:
Primary
- 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
- Compare the toxic effects of these regimens in these patients.
- 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.
- Compare the time to progression in patients treated with these regimens followed by
maintenance therapy comprising clarithromycin, thalidomide, and dexamethasone.
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.
PROJECTED ACCRUAL: A total of 130 patients will be accrued for this study.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
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 10^6 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
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
- FEV_1 ≥ 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
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
Locations and Contacts
Samuel Oschin Comprehensive Cancer Institute at Cedars-Sinai Medical Center, Los Angeles, California 90048, United States; Recruiting
Michael C. C. Lill, MD, Phone: 310-423-2997, Email: lillm@cshs.org
James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester, New York 14642, United States; Recruiting
Gordon L. Phillips, MD, Phone: 585-273-4399
St. Vincent's Comprehensive Cancer Center - Manhattan, New York, New York 10011, United States; Recruiting
Sundar Jagannath, MD, Phone: 888-442-2623, Email: sjaganna@salick.com
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States; Recruiting
Kathy Lilleby, Phone: 206-667-5836
Veterans Affairs Medical Center - Seattle, Seattle, Washington 98108, United States; Recruiting
Thomas R. Chauncey, MD, PhD, Phone: 206-764-2709
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: July 2005
Last updated: July 7, 2009
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