Rituximab and Cyclophosphamide in Treating Patients With High Risk, Refractory, or Relapsed Multiple Myeloma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with cyclophosphamide may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with cyclophosphamide works in treating patients with high risk, refractory, or relapsed multiple myeloma.

Detailed Description
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OBJECTIVES: Determine the effect of rituximab and high-dose cyclophosphamide on the growth of myeloma stem cells in patients with high-risk, refractory, or relapsed multiple myeloma. OUTLINE: Patients receive rituximab IV on days -10 and -7; once weekly for 4 weeks (after completion of high-dose cyclophosphamide); and then once in months 3, 6, 9, and 12. Patients also receive high-dose cyclophosphamide on days -3 to 0. PROJECTED ACCRUAL: Not specified.

Official Title
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Phase II Study of High Dose Cyclophosphamide and Rituximab in Multiple Myeloma

Conditions
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Multiple Myeloma and Plasma Cell Neoplasm

Intervention / Treatment
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* Biological: rituximab
* Drug: cyclophosphamide


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of multiple myeloma, meeting 1 of the following criteria: High-risk disease in first remission, as defined by the following: Beta-2 microglobulin > 5.0 mg/dL Chromosome 13 deletion Primary refractory disease Relapsed disease after achieving a response to prior chemotherapy The following diagnoses are not allowed: POEMS syndrome Plasma cell leukemia Amyloidosis Nonsecretory myeloma No evidence of spinal cord compression PATIENT CHARACTERISTICS: Age Over 18 Performance status Not specified Life expectancy Not specified Hematopoietic Not specified Hepatic Not specified Renal Not specified Other Not pregnant or nursing Fertile patients must use effective contraception HIV negative Has good organ function Is in good physical condition No active infection requiring antibiotics No other malignancy within the past 2 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix PRIOR CONCURRENT THERAPY: Biologic therapy No persistently detectable donor cells after prior allogeneic stem cell transplantation No prior rituximab Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy Not specified Surgery Not specified Other At least 28 days since prior therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: rituximab + cyclophosphamide<br>Rituximab 375 mg/m^2 on Days -10 and -7; Cyclophosphamide 50 mg/kg on days -3, -2, -1, and 0; Rituximab 375 mg/m^2 weekly x4 after platelet counts recover; For patients achieving at least stable disease, rituximab maintenance 375 mg/m^2 once each during months 3, 6, 9, and 12 | Biological: rituximab<br> <br> * Other names: Rituxan;Drug: cyclophosphamide<br> <br> * Other names: Cytoxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free Survival | Percentage of study participants who did not report that their multiple myeloma relapsed or progressed (got worse) | 1 year | 
| Safety of Maintenance Rituximab Following High Dose Cyclophosphamide |  | 2, 3, 6, 9, and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Toxicity |  | 2, 3, 6, 9, and 12 months | 
| Complete Response (CR) Rate and Partial Response (PR) Rate |  | 1 year | 
| Effect of Rituximab by Clonogenic Growth of Multiple Myeloma (MM) Progenitors and the Mechanisms by Which MM Stem Cells Are Inhibited |  | 2, 3, 6, 9, and 12 months | 
| Overall Survival |  | 5 years | 

 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, refractory multiple myeloma