Relapse Myeloma; Cyclofosfamide; Bortezomib; Maintenance

Study Overview
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Brief Summary
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Bortezomib and cyclophosphamide in combination with dexamethasone has already demonstrated high response rates in refractory multiple myeloma. Low dose continuous cyclophosphamide, also called metronomic scheduling, minimize toxic side effects and eliminate the obligatory rest periods. Combining cyclophosphamide with bortezomib might target distinct aspects of a myeloma functionality. The objectives of the present study are whether patients with refractory or relapsed multiple myeloma after reinduction with bortezomib, cyclophosphamide and dexamethasone will benefit from maintenance therapy with bortezomib and cyclophosphamide with acceptable side-effects. Recently two studies have shown with thalidomide that maintenance therapy might improve EFS and one study also the OS.

Official Title
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Bortezomib in Combination With Continuous Low-dose Oral Cyclophosphamide and Dexamethason Followed by Maintenance in Primary Refractory or Relapsed Bortezomib naïve Multiple Myeloma Patients. A Prospective Phase II Study.

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Bortezomib
* Drug: Cyclophosphamide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Stage II-III Multiple Myeloma Relapse or primary refractory disease after initial chemotherapy WHO performance status 0 - 2 Life expectancy of at least 6 weeks ANC (absolute neutrophil count) ≥ 1.0x109/l(or ≥ 0.5x109/l, if due to bone marrow infiltration by malignancy) Platelet count ≥ 75x109/l or ≥ 50x109/l, if due to bone marrow infiltration by malignancy) Written informed consent (present in patient's file) Patient is able and willing to use adequate contraception during therapy and for at least 1 month after study Patient has the ability to understand the requirements of the study Exclusion Criteria: Previous treatment with bortezomib Urine production < 1.5 l/24h Pre-existent polyneuropathy (grade 2 or higher, according to CTCAE 3.0) Pregnancy or positive pregnancy tests during study and for 1 month after final dose of thalidomide History of active malignancy during the past 5 years with the exception of basal carcinoma of the skin) Active uncontrolled infections Additional uncontrolled serious medical or psychiatric illness

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Bortezomib, cyclophosphamide, dexamethason<br>To assess the efficacy of bortezomib, cyclophosphamide and dexamethasone during re-induction and in maintenance therapy. To assess the safety of bortezomib, cyclophosphamide and dexamethasone during re-induction and in maintenance therapy in patients with refractory or relapsed multiple myeloma. | Drug: Bortezomib<br>* Re-induction chemotherapy with bortezomib, cyclophosphamide and dexamethasone. All patients with first relapse or primary refractory multiple myeloma and bortezomib naive will be given 6 cycles of re-induction therapy. Patients will be evaluated for response after cycle 3 and 6. Maintenance therapy with bortezomib and cyclophosphamide Maintenance therapy with bortezomib and cyclophosphamide will start at 4 weeks after the last cycle of re-induction chemotherapy if ANC ≥ 2.0 x 109/l and platelets > 75 x 109/l. Bortezomib is administered once every other week and cyclophosphamide (50 mg) every day for 1 year or until progression or death of any cause.<br>* Other names: Velcade;Drug: Cyclophosphamide<br>* Re-induction chemotherapy with bortezomib, cyclophosphamide and dexamethasone. All patients with first relapse or primary refractory multiple myeloma and bortezomib naive will be given 6 cycles of re-induction therapy. Patients will be evaluated for response after cycle 3 and 6. Maintenance therapy with bortezomib and cyclophosphamide Maintenance therapy with bortezomib and cyclophosphamide will start at 4 weeks after the last cycle of re-induction chemotherapy if ANC ≥ 2.0 x 109/l and platelets > 75 x 109/l. Bortezomib is administered once every other week and cyclophosphamide (50 mg) every day for 1 year or until progression or death of any cause.<br>* Other names: Endoxan;Drug: Dexamethasone<br>* Re-induction chemotherapy with bortezomib, cyclophosphamide and dexamethasone. All patients with first relapse or primary refractory multiple myeloma and bortezomib naive will be given 6 cycles of re-induction therapy. Patients will be evaluated for response after cycle 3 and 6. Maintenance therapy with bortezomib and cyclophosphamide Maintenance therapy with bortezomib and cyclophosphamide will start at 4 weeks after the last cycle of re-induction chemotherapy if ANC ≥ 2.0 x 109/l and platelets > 75 x 109/l. Bortezomib is administered once every other week and cyclophosphamide (50 mg) every day for 1 year or until progression or death of any cause.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity of induction chemotherapy according to CTCAE version 3.0 |  | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | 5 years | 
| Overall Survival |  | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bortezomib, cyclophosphamide, dexamethason, multiple myeloma