Clinical trial NCT01539083: Velcade (Bortezomib) Consolidation After Transplant
Official title: An Open-label, Randomised Trial of Bortezomib Consolidation (With Thalidomide and Prednisolone) Vs Thalidomide and Prednisolone Alone in Previously Untreated Subjects With Multiple Myeloma After Receiving Bortezomib, Cyclophosphamide, Dexamethasone (VCD) Induction and Autologous Stem Cell Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
Bortezomib
VELCADE
Consolidation therapy
Subcutaneous
Thalidomide
Prednisolone
Autologous stem cell transplant (ASCT)
VELCADE, cyclophosphamide, dexamethasone (VCD) induction therapy
Lead sponsor: Janssen Scientific Affairs, LLC
Sponsor class: INDUSTRY
First posted: 2012-02-27
Enrollment: 256
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Consolidation Phase: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) at Month 12
timeFrame: Month 12
Secondary outcomes:
measure: Consolidation Phase: Percentage of Participants With Complete Response (CR) at Months 3, 6, 9 and 12
timeFrame: Months 3, 6, 9 and 12
measure: Consolidation Phase: Percentage of Participants With Stringent Complete Response (sCR) at Months 3, 6, 9 and 12
timeFrame: Months 3, 6, 9 and 12
measure: Progression Free Survival (PFS)
timeFrame: Baseline until progressive disease (up to 5 years)
measure: Disease-free Survival (DFS)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Consolidation Phase: Change From Baseline in AQOL-6D Scores at the End of the Consolidation Phase
timeFrame: Baseline, Month 12
measure: Consolidation Phase: Change From Baseline in FACT/GOG-NTX Total Score at the End of the Consolidation Phase
timeFrame: Baseline, Month 12
Other outcomes:
Locations:
city: Adelaide
country: Australia
city: Camperdown
country: Australia
city: Geelong
country: Australia
city: Greenslopes
country: Australia
city: Heidelberg
country: Australia
city: Herston
country: Australia
city: Malvern
country: Australia
city: Melbourne
country: Australia
city: Nedlands
country: Australia
city: Newcastle
country: Australia
city: Prahran
country: Australia
city: Sydney
country: Australia
city: Westmead
country: Australia
city: Woodville South
country: Australia
city: Woolloongabba
country: Australia
city: Beijing
country: China
city: Guangzhou
country: China
city: Shanghai
country: China
city: Tianjin
country: China
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Jeollanam-do
country: Korea, Republic of
city: Ulsan
country: Korea, Republic of
Study officials:
affiliation: Janssen Asia-Pacific Medical Affairs
name: Janssen Asia-Pacific Medical Affairs Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Horvath N, Spencer A, Kenealy M, Joshua D, Campbell PJ, Lee JJ, Hou J, Qiu L, Kalff A, Khong T, Londhe A, Siggins S, van Kooten Losio M, Eisbacher M, Prince HM. Phase 3 study of subcutaneous bortezomib, thalidomide, and prednisolone consolidation after subcutaneous bortezomib-based induction and autologous stem cell transplantation in patients with previously untreated multiple myeloma: the VCAT study. Leuk Lymphoma. 2019 Sep;60(9):2122-2133. doi: 10.1080/10428194.2019.1579322. Epub 2019 Feb 19.