Multiple Myeloma
Conditions
Keywords
stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
Brief summary
RATIONALE: Thalidomide may stop the growth of cancer cells by stopping blood flow to the cancer. Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Giving thalidomide before and after peripheral stem cell transplant may be effective in treating newly diagnosed multiple myeloma. PURPOSE: This phase II trial is studying how well giving thalidomide with chemotherapy and peripheral stem cell transplant work in treating patients with newly diagnosed multiple myeloma.
Detailed description
OBJECTIVES: * Determine the efficacy and toxicity of thalidomide and dexamethasone as a pre-transplantation induction regimen in patients with multiple myeloma. * Determine, preliminarily, the safety and efficacy of prednisone and thalidomide maintenance therapy in these patients. * Correlate chromosome 13 abnormalities with therapeutic response in patients treated with this regimen. * Correlate specific subsets of chromosome aberrations with event-free and overall survival of patients treated with this regimen. * Evaluate immune reconstitution and recovery after first and second transplantation in these patients. OUTLINE: This is a multicenter study. * Induction chemotherapy: Patients receive oral thalidomide once daily on days 1-35 and oral dexamethasone once daily on days 1-4, 9-12, and 17-20. Treatment repeats every 35 days for 3 courses in the absence of disease progression or unacceptable toxicity. * Stem cell mobilization and collection: Beginning 5-7 days, but no more than 3 weeks, after completion of induction chemotherapy, patients receive cyclophosphamide IV over 45-60 minutes on day 0, filgrastim (G-CSF) subcutaneously (SC) on days 1-10, and sargramostim (GM-CSF) SC beginning on day 1 and continuing until completion of peripheral blood stem cell (PBSC) collection. Patients begin PBSC collection on day 11 or as soon as blood counts recover. * First transplantation: Within 3-6 weeks after cyclophosphamide administration, patients receive melphalan IV over 20 minutes on day -1. Patients undergo PBSC infusion on day 0. Patients receive GM-CSF SC or IV beginning on day 6 and continuing until blood counts recover. * Second transplantation: Between 2-4 months after first transplantation, patients undergo a second tandem melphalan and PBSC transplantation with GM-CSF support as above. * Maintenance therapy: Beginning 70-90 days post-transplantation, patients receive oral prednisone every other day and oral thalidomide once daily. Treatment continues in the absence of disease progression or unacceptable toxicity. Patients are followed every 12 months for 10 years. PROJECTED ACCRUAL: Approximately 99 patients will be accrued for this study within 18 months.
Interventions
BIOLOGICALfilgrastim
PBSC collection: 10 mcg/kg SQ days 1-10
BIOLOGICALsargramostim
PBSC collection: 500 mcg/m2 SQ day 1 through last apheresis 1st and 2nd trans: 500 mcg SC or IV days 6-WBC recovery
DRUGcyclophosphamide
PBSC collection: 1 mg/m2 IV over 45-60 mins day 0
DRUGdexamethasone
40 mg/d PO days 1-4, 9-12, 17-20
DRUGmelphalan
1. st trans: 140 mg/m2 IV over 20 mins day -1 2. nd trans: 200mg/m2 IV over 20 mins day -1
DRUGprednisone
maint: 50 mg/d PO every other day until progression
DRUGthalidomide
ind: 50 mg increased by 50 mg every week to max 400 mg PO qhs for 35 days maint: 50 mg/d increased by 50 mg every week to 200 mg PO daily until progression
PROCEDUREperipheral blood stem cell transplantation
2-4 x 10\^6/kg IV day 0
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Newly diagnosed multiple myeloma requiring treatment * Smoldering myeloma with evidence of progressive disease requiring chemotherapy * More than 25% increase in M component levels and/or Bence-Jones excretion or symptom development * Non-secretory patients with at least 30% bone marrow plasmacytosis * No IgM peaks unless there is evidence of more than 30% bone marrow plasmacytosis or more than 3 lytic lesions PATIENT CHARACTERISTICS: Age * 18 to 65 Performance status * Zubrod 0-2 OR * Zubrod 3-4 based solely on bone pain Life expectancy * Not specified Hematopoietic * No untreated, unresolved symptomatic hyperviscosity Hepatic * Hepatitis B negative Renal * Creatinine no greater than 3 mg/dL if in renal failure and on dialysis (after hydration and/or correction of hypercalcemia) Cardiovascular * No history of chronic cerebrovascular accident * No myocardial infarction within the past 6 months * No unstable angina * No congestive heart failure that is difficult to control * No uncontrollable hypertension * No cardiac arrhythmia that is difficult to control Pulmonary * No history of chronic obstructive or chronic restrictive pulmonary disease * No untreated, unresolved pneumonia * Pulmonary function tests (PFTs) at least 50% of predicted * DLCO at least 50% of predicted * Arterial partial pressure of oxygen greater than 70 if unable to complete PFTs due to bone pain or fracture Other * HIV negative * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No untreated, unresolved pathologic fractures * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use at least 2 highly effective methods of contraception for 4 weeks before, during, and for at least 4 weeks after study participation PRIOR CONCURRENT THERAPY: Biologic therapy * No more than 8 weeks of prior thalidomide therapy Chemotherapy * No prior chemotherapy for this disease Endocrine therapy * Prior steroid therapy allowed provided treatment duration was no more than 2 weeks Radiotherapy * No prior radiotherapy to more than 50% of the pelvis Surgery * Not specified
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Survival | 4-7 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assess Toxicity of Thalidomide/Dexamethasone as a Pre-transplant Induction Regimen. | Induction | To assess Grade 3-5 AE related to thalidomide/dexamethasone when administered as a pre-transplant induction regimen. |
Countries
United States
Participant flow
Recruitment details
Patients were recruited at participating cooperative group institutions.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Arm thalidomide/dexamethasone followed by tandem melphalan peripheral blood stem cell transplantation (with cyclophosphamide and filgrastim or sargramostim support) and prednisone/thalidomide maintenance | 142 |
| Total | 142 |
Baseline characteristics
| Characteristic | Treatment Arm |
|---|---|
| Age, Continuous | 57 years |
| Gender Female | 56 Participants |
| Gender Male | 86 Participants |
| Region of Enrollment United States | 142 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 140 / 140 | 105 / 105 | 74 / 76 |
| serious Total, serious adverse events | 7 / 140 | 0 / 105 | 1 / 76 |
Outcome results
Primary
Overall Survival
Time frame: 4-7 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction/PBSC Mobilization | Overall Survival | .64 proportion surviving at 4 years |
Comparison: The study was designed to have 82% power for detecting a 50% improvement in survival from a median of 4 years, as observed in SWOG S9321.95% CI: [55, 74]Kaplan and Meier
Secondary
Assess Toxicity of Thalidomide/Dexamethasone as a Pre-transplant Induction Regimen.
To assess Grade 3-5 AE related to thalidomide/dexamethasone when administered as a pre-transplant induction regimen.
Time frame: Induction
Population: All participants receiving at least one dose of induction therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Induction/PBSC Mobilization | Assess Toxicity of Thalidomide/Dexamethasone as a Pre-transplant Induction Regimen. | 2 Participants |