Relapse Myeloma; Cyclofosfamide; Bortezomib; Maintenance

NCT ID: NCT02467010

Last Updated: 2015-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2013-07-31

Brief Summary

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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bortezomib, cyclophosphamide, dexamethason

• 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.

Group Type: EXPERIMENTAL

Bortezomib

Intervention Type: DRUG

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.

Cyclophosphamide

Intervention Type: DRUG

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.

Dexamethasone

Intervention Type: DRUG

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.

Interventions

Bortezomib

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.

Intervention Type: DRUG

Cyclophosphamide

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.

Intervention Type: DRUG

Dexamethasone

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.

Intervention Type: DRUG

Other Intervention Names

Velcade; Endoxan

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: lead

Responsible Party

E. Vellenga

Prof.dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sjoerd Hovenga

Role: PRINCIPAL_INVESTIGATOR

Nij Smellinghe Hospital Drachten

Locations

University Medical Center Groningen

Groningen, Provincie Groningen, Netherlands

Countries

Netherlands

Other Identifiers

2008-004822-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UMCG REMM

Identifier Type: -

Identifier Source: org_study_id