S9922 Combination Chemo Plus Filgrastim With or Without Thalidomide in Refractory Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Thalidomide may stop the growth of tumor cells by stopping blood flow to the tumor. It is not yet known if combination chemotherapy is more effective with or without thalidomide for multiple myeloma. PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without thalidomide in treating patients who have refractory multiple myeloma.

Detailed Description
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OBJECTIVES: I. Compare the overall and progression-free survival and remission rates in patients with refractory multiple myeloma treated with dexamethasone, cyclophosphamide, etoposide, cisplatin, and filgrastim (G-CSF) with or without thalidomide. II. Compare the qualitative and quantitative toxic effects of these regimens in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior transplantation (yes vs no), prior treatment failure (resistant vs relapsing), prior treatment regimens (1-2 vs 3-4), and prior thalidomide (no vs some). Patients are randomized to one of two treatment arms. Arm I: Patients receive oral dexamethasone daily and cyclophosphamide, etoposide, and cisplatin (DCEP) IV continuously on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously daily beginning on day 5 and continuing until blood counts recover. Treatment continues every 3-4 weeks for 3 courses. Patients achieving stable disease or better proceed to maintenance chemotherapy with DCEP administered every 8 weeks for 3 additional courses. Arm II: Patients receive chemotherapy with DCEP as in arm I plus oral thalidomide daily. Thalidomide continues with maintenance chemotherapy and then continues after chemotherapy is completed until disease progression. Patients are followed every 3 months for 1 year, every 6 months for 1 year, and then annually for 3 years. PROJECTED ACCRUAL: A total of 320 patients will be accrued for this study within 4 years.

Official Title
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A Phase III Trial of Dexamethasone, Cyclophosphamide, Etoposide, Cisplatin (DCEP) and G-CSF With or Without Thalidomide (NSC #66847) as Salvage Therapy for Patients With Refractory Multiple Myeloma

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Biological: filgrastim
* Drug: cisplatin
* Drug: cyclophosphamide
* Drug: dexamethasone
* Drug: etoposide
* Drug: thalidomide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed stage I, II, or III multiple myeloma with protein criteria present Quantifiable M-components of IgG, IgA, IgD, IgE AND/OR Urinary kappa or lambda light chain excretion No IgM peaks Quantifiable monoclonal proteins Received at least 1, but no more than 4 prior treatment regimens, including the following: Chemotherapy Bone marrow transplantation Biologic therapy Radiotherapy Interferon therapy or steroid pulsing given as maintenance therapy after transplantation or chemotherapy is not considered a separate treatment regimen Progressive disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-2 (3-4 allowed if due solely to bone pain) Life expectancy: At least 3 months Hematopoietic: Absolute granulocyte count at least 1,000/mm3 Platelet count at least 50,000/mm3 (at least 50% plasma cells in bone marrow) Hepatic: Bilirubin no greater than 2.5 times upper limit of normal (ULN) SGOT or SGPT no greater than 2.5 times ULN Renal: Creatinine no greater than 2.0 mg/dL OR Creatinine clearance at least 60 mL/min Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use 2 methods of effective contraception for 4 weeks before, during, and for 4 weeks after study No other prior or concurrent malignancies within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or any other adequately treated stage I or II cancer in complete remission No grade 2 or greater preexisting peripheral neuropathy PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Prior thalidomide allowed if received less than 3 months of therapy Recovered from prior biologic therapy Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy and recovered No other concurrent chemotherapy Endocrine therapy: See Disease Characteristics No concurrent hormonal therapy Radiotherapy: See Disease Characteristics At least 3 weeks since prior extensive or limited radiotherapy and recovered No concurrent radiotherapy Surgery: Not specified

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemo with thalidomide<br>chemo with thalidomide | Biological: filgrastim<br>* Arms 1 and 2: 300 mcg (pts </= 60 kg) or 480 mcg (pts > 60 kg), SC beginning day 5<br>* Other names: G-CSF;Drug: cisplatin<br>* Arms 1 and 2: 15 mg/m2/d continuous IV days 1-4<br>* Other names: platinol;Drug: cyclophosphamide<br>* Arms 1 and 2: 400 mg/m2/d continuous IV days 1-4<br>* Other names: cytoxan;Drug: dexamethasone<br>* Arms 1 and 2: 40 mg/d PO days 1-4<br>* Other names: decadron;Drug: etoposide<br>* Arms 1 and 2: 40 mg/m2/d continuous IV days 1-4<br>* Other names: VP-16;Drug: thalidomide<br>* Arm 2: 800 mg/d (max dose) PO daily<br>* Other names: thalomid;|
| Active Comparator: chemo without thalidomide<br>chemo without thalidomide | Biological: filgrastim<br>* Arms 1 and 2: 300 mcg (pts </= 60 kg) or 480 mcg (pts > 60 kg), SC beginning day 5<br>* Other names: G-CSF;Drug: cisplatin<br>* Arms 1 and 2: 15 mg/m2/d continuous IV days 1-4<br>* Other names: platinol;Drug: cyclophosphamide<br>* Arms 1 and 2: 400 mg/m2/d continuous IV days 1-4<br>* Other names: cytoxan;Drug: dexamethasone<br>* Arms 1 and 2: 40 mg/d PO days 1-4<br>* Other names: decadron;Drug: etoposide<br>* Arms 1 and 2: 40 mg/m2/d continuous IV days 1-4<br>* Other names: VP-16;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | Length of time until progression - 25% increase from the baseline in myeloma protein production of other signs of disease progression such as hypercalcemia. | 18 months | 

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