Velcade (Bortezomib) Consolidation After Transplant (VCAT)

Janssen (J&J Innovative Medicine)

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Thalidomide; Drug: Bortezomib; Drug: Cyclophosphamide; Drug: Prednisolone; Drug: Dexamethasone

Study type: Interventional

Funder types: Industry

Identifiers

NCT01539083

26866138-MMY-2073 (Other Identifier)

CR018751

Details and patient eligibility

About

The purpose of this study is to determine if bortezomib when added to consolidation treatment with thalidomide and prednisolone leads to an improved response in patients with multiple myeloma who have undergone autologous stem cell transplant and initial treatment with bortezomib, cyclophosphamide, and dexamethasone.

Full description

This is an open-label (patients will know the identity of study treatments), randomized (patients will be assigned by chance to different treatments) study of bortezomib administered as consolidation therapy (therapy given once a remission is achieved) with thalidomide and prednisolone versus thalidomide and prednisolone alone in previously untreated patients with multiple myeloma. Multiple myeloma is a cancer of your plasma cells, a type of white blood cell present in your bone marrow. Patients in this study will receive initial therapy with bortezomib, cyclophosphamide, and dexamethasone (referred to as VCD induction therapy) and will undergo autologous stem cell transplant (ASCT) (a procedure where patients receive an infusion of immature blood cells [stem cells] from their own body to replenish the body's supply of healthy blood-forming cells) before randomization to one of two treatments: Treatment A (thalidomide for up to 12 months or until disease progression and prednisolone on alternate days continued indefinitely or until disease progression) or Treatment B (bortezomib for 32 weeks in addition to thalidomide up to 12 months or until disease progression and prednisolone on alternate days, continued indefinitely or until disease progression.

Throughout the study, the patient's response to therapy will be assessed according to protocol-defined efficacy evaluations and by implementing defined disease response criteria (International Myeloma Working Group [IMWG] criteria). Safety will be evaluated throughout the study. Follow up for progression-free survival (PFS) and overall survival (OS) will be conducted from time of randomization to 3 years post-randomization.

Two interim analyses are planned. The final analysis will be conducted after all patients have completed 12-month consolidation treatment phase or discontinued. The primary endpoint of number and percent of patients with complete response and very good partial response defined by IMWG criteria for multiple myeloma will be examined in the interim and final analyses after approximately 12 months of consolidation therapy. At the completion of the study, updated analyses of PFS and OS will be performed.

Enrollment: 256 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Previously diagnosed with multiple myeloma based on international myeloma working group (IMWG) criteria.and meet all of the following; Serum M-protein greater than or equal to (>=) 1 gram per deciliter (g/dL) (>=10 gram per liter); Urine M-protein >=200 milligram (mg) per 24 hour and Serum Free Light chain (FLC) assay: Involved FLC Level >=10 mg/dL (>=100 mg/L) provided serum FLC ratio is normal
• Meet the pretreatment laboratory criteria as specified in the study protocol at and within 21 days before baseline (Day 1 of Cycle 1, before bortezomib administration for induction).
• Have ECOG status 0-2.
• Men and women must practice an appropriate method of birth control as specified in the study protocol from signing of the informed consent form though to the 12-month visit/early termination visit.

Exclusion criteria

• Has previously received treatment for multiple myeloma (including prior therapy with radiation or pulsed dexamethasone) as specified in the study protocol.
• Has a history of any other malignancy within 5 years before enrolment as specified in the study protocol.
• Has had major surgery as specified in the study protocol within 30 days before enrolment.
• Had a myocardial infarction within 6 months of enrolment or has New York Heart Association (NYHA) Class III or IV heart failure (or other clinically significant cardiac medical history as specified in the study protocol).
• Has any condition that, in the opinion of the investigator, would make participation not be in the best interest (eg, compromise the well-being) of the patient or that could prevent, limit, or confound the protocol-specified assessments.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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256 participants in 3 patient groups

Bortezomib + Cyclophosphamide + Dexamethasone [VCD Induction]

Experimental group

Description:

Bortezomib (Velcade) 1.3 milligram per square meter (mg/m\^2) subcutaneously (SC) on Days 1, 4, 8, and 11; cyclophosphamide 300 mg/m\^2 orally on Days 1, 8, and 15; and dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 in three 21-day treatment cycles. Participants who completed induction phase entered into the consolidation treatment phase.

Treatment:

Drug: Dexamethasone

Drug: Cyclophosphamide

Drug: Bortezomib

Thalidomide + Prednisolone [TP Consolidation]

Experimental group

Description:

Thalidomide 100 mg orally, once daily until disease progression (up to maximum of 12 months) and prednisolone 50 mg orally, on every alternate day until disease progression.

Treatment:

Drug: Prednisolone

Drug: Thalidomide

Bortezomib + Thalidomide + Prednisolone [VTP Consolidation]

Experimental group

Description:

Bortezomib 1.3 mg/m\^2 SC every 2 weeks for 32 weeks in addition to thalidomide 100 mg orally, once daily for a maximum of 12 months or until disease progression and prednisolone 50 mg orally, on every alternate day until disease progression.

Treatment:

Drug: Prednisolone

Drug: Bortezomib

Drug: Thalidomide