Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma
N/A
65 Years
Both
Multiple Myeloma and Plasma Cell Neoplasm
Trial Information
Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma
OBJECTIVES:
- Determine the feasibility and toxic effects of high-dose melphalan, busulfan, and
cyclophosphamide followed by autologous peripheral blood stem cell rescue, interferon
alfa, and pamidronate in patients with responsive or stable, low-bulk multiple myeloma.
- Determine the response rate and progression-free and overall survival of patients
treated with this regimen.
- Determine the feasibility of adding thalidomide to interferon alfa and pamidronate in
patients who are not in complete remission (CR) 6 months after the second course of
high-dose chemotherapy.
- Determine whether administration of thalidomide can increase the CR rate in patients
who are not in CR 6 months after the second course of high-dose chemotherapy and
determine its effect on progression-free and overall survival of these patients.
- Determine the pharmacokinetics of busulfan and cyclophosphamide and correlate the
pharmacokinetics with the toxic effects of these drugs and outcome in these patients.
- Determine the effect of thalidomide on microvascular density of bone marrow and
correlate these possible effects with outcome in these patients.
- Determine the cytogenetics, gene rearrangement, and fluorescence in situ hybridization
in baseline and post treatment bone marrow and blood specimens and correlate the
presence/persistence of these features with treatment outcome in these patients.
OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF)
subcutaneously (SC) or IV twice a day beginning on day 2 and continuing until peripheral
blood stem cells (PBSCs) are collected. PBSCs are collected beginning on day 10.
Patients receive high-dose melphalan IV on day -1. PBSCs are reinfused on day 0. G-CSF is
administered IV or SC daily beginning on day 1 and continuing until blood counts recover.
Between 8 and 14 weeks later, patients receive high-dose busulfan IV every 6 hours on days
-7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBSCs are reinfused on day
0 and G-CSF is administered IV or SC daily until blood counts recover.
Patients with responding or stable disease after chemotherapy receive maintenance therapy
with interferon alfa beginning 14-20 weeks after day 0 of the second course of chemotherapy.
Interferon alfa is administered SC 3 times a week for 3 years. Patients also receive
pamidronate IV every 4 weeks until disease progression. Patients who are not in complete
remission (CR) 6 months after completing the second course of chemotherapy receive oral
thalidomide daily for a maximum of 1 year or for 3 months after achieving CR.
Patients are followed monthly for 1 year, every 3 months for 1 year, and then periodically
thereafter.
PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within
approximately 2.5 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically proven stage I-III multiple myeloma
- Less than 18 months since diagnosis
- Smoldering myeloma allowed if there is evidence of progressive disease requiring
therapy
- At least 25% increase in M protein levels or Bence Jones excretion
- Hemoglobin no greater than 10.5 g/dL
- Hypercalcemia
- Frequent infections
- Rise in serum creatinine above normal on 2 separate occasions
- Nonquantifiable monoclonal proteins allowed if other criteria for multiple
myeloma or smoldering myeloma are met
- Response/status after induction therapy:
- Responding or stable disease AND no greater than 40% myelomatous involvement of
bone marrow
- No Waldenstrom's macroglobulinemia
PATIENT CHARACTERISTICS:
Age:
- 65 and under
Performance status:
- Karnofsky 80-100%
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count greater than 100,000/mm^3
Hepatic:
- Bilirubin no greater than 1.5 mg/dL
- SGOT and SGPT less than 2.5 times upper limit of normal
- Hepatitis B antigen or hepatitis C RNA negative
Renal:
- See Disease Characteristics
- Creatinine no greater than 1.4 mg/dL
- Creatinine clearance greater than 65 mL/min
Cardiovascular:
- Cardiac ejection fraction at least 50% by MUGA or echocardiogram
Pulmonary:
- FEV_1 greater than 60%
- DLCO greater than 50% of predicted lower limit
Other:
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No other medical or psychosocial problems that would increase patient risk
- No other malignancy within past 5 years except nonmelanomatous skin cancer or
carcinoma in situ of the cervix
- No known hypersensitivity to filgrastim (G-CSF) or E. coli-derived proteins
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- See Disease Characteristics
- No more than 3 prior chemotherapy regimens
- At least 4 weeks since prior chemotherapy
Endocrine therapy:
- Not specified
Radiotherapy:
- At least 4 weeks since prior radiotherapy
Surgery:
- Not specified
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
George Somlo, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
City of Hope Medical Center
Authority:
United States: Federal Government
Study ID:
99021
NCT ID:
NCT00004088
Start Date:
April 1999
Completion Date:
Related Keywords:
- Multiple Myeloma and Plasma Cell Neoplasm
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- Neoplasms
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
Name | Location |
|---|---|
| City of Hope Comprehensive Cancer Center | Duarte, California 91010 |
| Banner Good Samaritan Medical Center | Phoenix, Arizona 85006 |
