S0204 Thalidomide, Chemotherapy, and Peripheral Stem Cell Transplant in Treating Patients With Multiple Myeloma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase II Trial Of Thalidomide/Dexamethasone Induction Followed By Tandem Melphalan Transplant And Prednisone/Thalidomide Maintenance (A BMT Study)

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: filgrastim
* Biological: sargramostim
* Drug: cyclophosphamide
* Drug: dexamethasone
* Drug: melphalan
* Drug: prednisone
* Drug: thalidomide
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment arm<br>thalidomide/dexamethasone followed by tandem melphalan peripheral blood stem cell transplantation (with cyclophosphamide and filgrastim or sargramostim support) and prednisone/thalidomide maintenance | Biological: filgrastim<br>* PBSC collection: 10 mcg/kg SQ days 1-10<br>* Other names: G-CSF;Biological: sargramostim<br>* PBSC collection: 500 mcg/m2 SQ day 1 through last apheresis 1st and 2nd trans: 500 mcg SC or IV days 6-WBC recovery<br>* Other names: GM-CSF;Drug: cyclophosphamide<br>* PBSC collection: 1 mg/m2 IV over 45-60 mins day 0<br>* Other names: cytoxan;Drug: dexamethasone<br>* 40 mg/d PO days 1-4, 9-12, 17-20<br>* Other names: decadron;Drug: melphalan<br>* st trans: 140 mg/m2 IV over 20 mins day -1 nd trans: 200mg/m2 IV over 20 mins day -1<br>Drug: prednisone<br>* maint: 50 mg/d PO every other day until progression<br>* Other names: steroid;Drug: thalidomide<br>* 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<br>* Other names: thalomid;Procedure: peripheral blood stem cell transplantation<br>* 2-4 x 10^6/kg IV day 0<br>* Other names: stem cell transplant;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival |  | 4-7 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Induction | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma