Clinical trial NCT00908232
Conditions: Multiple Myeloma
Keywords: multiple myeloma bortezomib hematology bone marrow cancer immunoglobulin refractory progression dexamethasone lenalidomide cyclophosphamide
Sponsor: Janssen-Cilag International NV
Start date: 2008-05-01; Completion date: 2011-08-01
Enrollment: 163 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to test the effectiveness and safety of adding cyclophosphamide or lenalidomide to the VD combination in the treatment of patients with multiple myeloma that have achieved a stable response after 4 initial cycles of treatment with VD. Multiple myeloma is the second most common cancer of the blood. Bortezomib disrupts the life cycle of the cell, affecting numerous biologic pathways, including those related to growth and survival of cancer cells.

Detailed description:
It has been shown that quality of response corresponds with clinical benefit. Stable disease is not regarded as a satisfactory result of therapy for relapsed and refractory multiple myeloma. However, there is no consensus if, when and how treatment should be continued or changed in the case of stable disease.

There are different strategies of achieving an optimal quality of response in relapsed and refractory multiple myeloma. One is to treat for a longer duration with one regimen. The alternative path can be a sequential approach adding another agent to the initial regimen depending on the outcome of therapy after a defined treatment period. These two principles will be evaluated in the present study.

Both Cyclophosphamide and Lenalidomide have proven to be efficacious in multiple myeloma and combinations of both agents with bortezomib and Dexamethasone have been shown to be active and tolerable.

In this study patients with relapsed/progressive or refractory multiple myeloma will start treatment with bortezomiib and Dexamethasone. Response will be evaluated after four cycles. Patients with complete, very good partial response or partial response will continue treatment as initiated. Patients with stable disease will either continue treatment with the bortezomib/Dexamethasone combination for another four cycles or will receive Cyclophosphamide or Lenalidomide as an additional third agent for another four cycles.

Patients with multiple myeloma that are refractory to or have relapsed/progressed after primary treatment for multiple myeloma will be enrolled in the study. All patients will receive a combination of bortezomib plus dexamethasone for a total of four cycles. Based on the response to this treatment, further study treatment is customized. Patients with a complete, a very good partial or a partial response will continue to receive bortezomib and Dexamethasone for a maximum additional four cycles, to an overall maximum of eight cycles. Patients achieving stable disease, as defined by International Myeloma Working Group 2006 (IMWG 2006) response criteria, will undergo a central randomisation to continue treatment with VD or VD plus cyclophosphamide or VD plus lenalidomide. Patients with progressive disease will go off study treatment. After randomisation, patients will receive therapy for up to four additional treatment cycles, to an overall maximum of eight cycles. Each cycle will consist of three weeks treatment. There will be a long-term follow-up period with monthly visits until relapse or progressive disease. Thereafter follow-up for survival will be continued by at least a phone call every other month. This will be performed for all patients until the last patient was treated and followed up for 1 year.

Safety will be assessed by the monitoring of adverse events, physical examination (including neurological/peripheral neurological examinations), pulmonary examinations, vital signs measurements, and clinical laboratory tests.

Patients will be treated in a 3-week cycle, up to a maximum of 8 cycles bortezomib 1.3 mg/m2 will be administered on day 1, 4, 8 and 11 as i.v. bolus infusion.

Dexamethasone 20 mg po will be administered on days 1, 2, 4, 5, 8, 9, 11, 12. Dexamethasone will be administered as 2 tables of 8 mg plus 1 tablet of 4 mg Cyclophosphamide 500 mg po will be administered as 10 tablets of 50 mg on day 1, 8, 15 Lenalidomide will be administered as once daily 10 mg tablet from day 1 to 14

Arms: arm 1: Stable disease after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8 arm 2: Stable disease after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8 and 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8 and cyclophosphamide 500 mg, orally daily, days 1, 8 and 15 for cycle 5 to 8 arm 3: Stable disease after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8 and 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8 and lenalidomide 10 mg orally daily from day 1 to day 14 for cycle 5 to 8 arm 4: Complete, very good partial or partial response after 4 cycles bortezomib + dexamethasone: bortezomib 1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 in combination with dexamethasone 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycle 1 to 8
Interventions: intervention 1: Cyclophosphamide intervention 2: Bortezomib intervention 3: Dexamethasone intervention 4: Lenalidomide
Intervention descriptions: intervention 1: 500 mg, p.o daily, days 1, 8 and 15 for cycles 5 to 8 cycles intervention 2: 1.3 mg/m2 IV bolus on Day 1, 4, 8, 11 for cycles 1 to 8 intervention 3: 20 mg orally daily, on Days 1, 2, 4, 5, 8, 9, 11, 12 for cycles 1 to 8 intervention 4: 10 mg orally daily, days 1-14 for cycles 5 to 8

Protocol documents: