Clinical trial NCT00507442: Phase 1/2 Study of VELCADE® in Combination With Other Drugs to Treat Previously Untreated Multiple Myeloma Patients
Official title: Phase 1/2 Study of VELCADE® (Bortezomib), Dexamethasone, and Revlimid® (Lenalidomide) Versus VELCADE, Dexamethasone, Cyclophosphamide, and Revlimid Versus VELCADE, Dexamethasone and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: Treatment for patients with multiple myeloma
who have received no prior treatment
Lead sponsor: Millennium Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
First posted: 2007-07-26
Enrollment: 158
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 Phase 1/2 study is to evaluate the efficacy and safety of treatment with VELCADE, dexamethasone, and Revlimid® (VDR) as well as VELCADE, dexamethasone, cyclophosphamide, and Revlimid (VDCR) in patients with multiple myeloma who have received no prior treatment. This study will evaluate whether the addition of Revlimid to VELCADE and Dexamethasone will increase the complete response (CR)/ very good partial response (VGPR) rate.


Eligibility criteria: Inclusion Criteria:

* Voluntary written informed consent
* Male or female subject 18 years of age or older
* A Karnofsky Performance Status score of ≥50% (Eastern Cooperative Oncology Group Performance Status score ≤2)
* Subjects must have symptomatic myeloma or asymptomatic myeloma with myeloma-related organ damage
* Diagnosed Multiple myeloma
* Subjects must have measurable disease requiring systemic therapy
* Subjects must not have been treated previously with any systemic therapy for multiple myeloma
* Two weeks must have elapsed since the date of the last radiotherapy treatment
* Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (1 highly effective method and 1 additional effective method) used at the same time, beginning at least 4 weeks before initiation of Revlimid treatment. Women must also agree to ongoing pregnancy testing
* Men must agree to not father a child and agree to use a latex condom during therapy and for 4 weeks after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential
* All subjects must agree to comply with the requirements of the RevAssistSM program

Exclusion Criteria:

* History of allergy to any of the study medications, their analogues, or excipients in the various formulations
* ≥Grade 2 peripheral neuropathy on clinical examination
* Myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities.
* Female subject who is pregnant or breast-feeding
* Clinically relevant active infection or serious comorbid medical conditions
* Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical or psychiatric illness likely to interfere with participation in this clinical study
* Active prior malignancy diagnosed or treated within the last 3 years

Primary outcomes:
measure: Number of Patients With Combined Complete Response and Very Good Partial Response
timeFrame: Up to 48 weeks or until disease progression
Secondary outcomes:
measure: Number of Patients With Adverse Events (AEs)
timeFrame: From first dose of study drug through the 30 day post-treatment AE assessment visit
measure: Number of Patients With Overall Response
timeFrame: Up to 48 weeks or until disease progression
measure: Number of Patients With Stringent Complete Response Rate
timeFrame: Up to 48 weeks or until disease progression
measure: Number of Patients With Complete Response Rate + Near Complete Response Rate
timeFrame: Up to 48 weeks or until disease progression
measure: Duration of Response
timeFrame: Up to 48 weeks or until disease progression
measure: Time to Disease Progression
timeFrame: Up to 48 weeks or until disease progression
measure: Time to Response
timeFrame: Up to 48 weeks or until disease response
measure: Progression-free Survival
timeFrame: Up to 48 weeks or until disease progression/death
measure: Probability of 1-year Survival
timeFrame: survival probability at 1 year after randomization
measure: Overall Survival
timeFrame: Up to 48 weeks or until death
Other outcomes:
Locations:
city: Denver
country: United States
facility: Rocky Mountain Cancer Center
state: Colorado
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, Stewart AK, Turturro F, Rifkin R, Wolf J, Estevam J, Mulligan G, Shi H, Webb IJ, Rajkumar SV. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10;119(19):4375-82. doi: 10.1182/blood-2011-11-395749. Epub 2012 Mar 15.
citation: Kumar SK, Flinn I, Noga SJ, Hari P, Rifkin R, Callander N, Bhandari M, Wolf JL, Gasparetto C, Krishnan A, Grosman D, Glass J, Sahovic EA, Shi H, Webb IJ, Richardson PG, Rajkumar SV. Bortezomib, dexamethasone, cyclophosphamide and lenalidomide combination for newly diagnosed multiple myeloma: phase 1 results from the multicenter EVOLUTION study. Leukemia. 2010 Jul;24(7):1350-6. doi: 10.1038/leu.2010.116. Epub 2010 May 27.