Study of Bortezomib and Dexamethasone With or Without Cyclophosphamide in Patients With Relapsed or Not Controllable Multiple Myeloma

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT00813150

2008-003213-27 (EudraCT Number)

CR015247

26866138MMY3022 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to compare bortezomib, dexamethasone and cyclophosphamide to bortezomib and dexamethasone alone for primary refractory or relapsed multiple myeloma.

Full description

This is a prospective, multi-centre, randomized (the study drug is assigned by chance), controlled, open-label (all people involved in the study know the identity of the assigned drug), parallel (each group of patients will be treated at the same time) group phase III study to determine the efficacy of the standard therapy of bortezomib and low dose dexamethasone in combination with or without continuous low dose oral cyclophosphamide for primary refractory or relapsed myeloma patients (1st - 3rd relapse). The study will consist of screening period, which may last from day -14 until day -1 before application of the first dose of bortezomib (on cycle 1, day 1), treatment phase begins on cycle 1 day 1 and continues until completion or discontinuation of all study drugs and follow-up phase. All patients will be followed up after end of treatment regardless of their response. Eligible patients will be randomized in 1:1 ratio to receive either treatment arms (Group A: receiving bortezomib plus dexamethasone or Group B receiving bortezomib plus dexamethasone plus cyclophosphamide). Patients will receive up to eight 3-weeks treatment cycles, unless they experience either unacceptable toxicity or if the patients request to withdraw from the study. The maximum number of cycles is dependent on patient response and investigator's discretion. It is recommended that patients with a confirmed complete response (CR) receive 2 additional cycles beyond a confirmation. Patients who do not achieve a CR but a partial response will receive a total of 8 cycles. For patients achieving stable disease it is within the investigator's discretion to continue study treatment beyond 6 cycles, after discussion with the sponsor. After completion of treatment the patients will be followed up every 12 weeks for up to 72 weeks. If the study is still ongoing a further follow up period will be done every 26 weeks until study end, or until the patient reaches progressive disease or start of alternative anti-myeloma therapy, if earlier. In case progressive disease (PD) has already been established during the treatment phase the patients will not enter the follow-up phase. In case of PD or start of alternative anti-myeloma treatment before the end of study the follow-up phase will be discontinued for the patient but the date of death of the patient will be documented (if applicable) before the end of study.

Enrollment: 96 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Previously diagnosed with multiple myeloma
• Primary refractory multiple myeloma or relapsed following 1 to 3 previous lines of therapy
• Karnofsky performance status must be equal to 60 percentage (ie, better or equal performance than requiring some help and taking care of most personal requirements)
• Has life expectancy estimated at screening must be of at least 6 months
• Agrees to protocol-defined use of effective contraception

Exclusion criteria

• Not received more than three previous lines of therapy for multiple myeloma
• Not received nitrosoureas or any other chemotherapy or immunotherapy or antibody therapy for multiple myeloma within 6 to 8 weeks before enrolment. Plasmapheresis must not be applied within 2 weeks before enrolment
• Patients with peripheral neuropathy or neuropathic pain of Grade 2 or greater intensity
• Patients with poorly controlled cardio vascular, vascular, pulmonary, gastro-intestinal, endocrine, neurological, psychiatric, hepatic, renal or metabolic diseases or hematological disorders
• Not have oligosecretory or non-secretory multiple myeloma

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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96 participants in 2 patient groups

Vd (bortezomib + dexamethasone)

Experimental group

Description:

Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle.

Treatment:

Drug: Bortezomib

Drug: Dexamethasone

Vcd (bortezomib + low-dose dexamethasone + cyclophosphamide)

Active Comparator group

Description:

Participants received bortezomib at a dose of 1.3 mg/m² body surface area (BSA) for eight 3-week cycles. Within each cycle it was administered twice weekly (on Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12 through 21). They received single oral doses of 20 mg dexamethasone on Days 1 and 2, 4 and 5, 8 and 9, and 11 and 12 of each cycle and single oral doses of 50 mg cyclophosphamide on a once daily basis from Day 1, Cycle 1 continuously until Day 21, Cycle 8.

Treatment:

Drug: Bortezomib

Drug: Cyclophosphamide

Drug: Dexamethasone