Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma
filgrastim
+ recombinant interferon alfa
+ busulfan
Blood Protein Disorders+12
+ Cardiovascular Diseases
+ Hematologic Diseases
Treatment Study
Summary
Study start date: April 13, 1999
Actual date on which the first participant was enrolled.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.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.77 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Until 65 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
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 Serum glutamic axaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) less than 2.5 times upper limit of normal Hepatitis B antigen or hepatitis C ribonucleaic acid (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 multigated acquisition scan (MUGA) or echocardiogram Pulmonary: Forced-expiratory volume in one second (FEV_1) greater than 60% of normal Diffusing capacity for carbon monoxide (DLCO) greater than 50% of predicted lower limit Other: Not pregnant Negative pregnancy test Fertile patients must use effective contraception Human immunodeficiency virus (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 Escherechi 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
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 2 locations
Banner Good Samaritan Medical Center
Phoenix, United StatesOpen Banner Good Samaritan Medical Center in Google MapsCity of Hope Comprehensive Cancer Center
Duarte, United States