Phase 1/2 Study of VELCADE® in Combination With Other Drugs to Treat Previously Untreated Multiple Myeloma Patients

NCT00507442 | Completed Phase 1 Results

• 1 other identifier: C05008
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Myeloma

Keywords

Treatment for patients with multiple myeloma; who have received no prior treatment

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Combined Complete Response and Very Good Partial Response

  Complete response requires negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \< 5% plasma cells in bone marrow. Very good partial response requires serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \< 100 mg per 24 h

  Up to 48 weeks or until disease progression

Secondary Outcomes (10)

• Number of Patients With Adverse Events (AEs)

  From first dose of study drug through the 30 day post-treatment AE assessment visit

• Number of Patients With Overall Response

  Up to 48 weeks or until disease progression

• Number of Patients With Stringent Complete Response Rate

  Up to 48 weeks or until disease progression

• Number of Patients With Complete Response Rate + Near Complete Response Rate

  Up to 48 weeks or until disease progression

• Duration of Response

  Up to 48 weeks or until disease progression

Study Arms (4)

VDR

EXPERIMENTAL

VELCADE (bortezomib), dexamethasone, and Revlimid (lenalidomide)

Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: Revlimid (lenalidomide)

VDCR

EXPERIMENTAL

VELCADE (bortezomib), dexamethasone, cyclophosphamide, Revlimid (lenalidomide)

Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: cyclophosphamide; Drug: Revlimid (lenalidomide)

VDC

EXPERIMENTAL

VELCADE (bortezomib), dexamethasone, cyclophosphamide

Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: cyclophosphamide

VDC-mod

EXPERIMENTAL

Modified dosing of VELCADE (bortezomib), dexamethasone, cyclophosphamide

Drug: VELCADE (bortezomib); Drug: dexamethasone; Drug: cyclophosphamide

Interventions

VELCADE (bortezomib) DRUG

bortezomib 1.3 mg/m\^2 given via IV on days 1, 4, 8, and 11 of a 3-week cycle for 8 cycles, then on days 1, 8, 15 and 22 of a 6-week cycle for 4 cycles (maintenance).

VDC; VDC-mod; VDCR; VDR

dexamethasone DRUG

dexamethasone 40 mg orally on days 1, 8, and 15 of a 3-week cycle for 8 cycles, then stop

VDC; VDC-mod; VDCR; VDR

cyclophosphamide DRUG

cyclophosphamide 500 mg/m\^2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop

VDC; VDC-mod; VDCR

Revlimid (lenalidomide) DRUG

lenalidomide 25 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDR arm) lenalidomide 15 mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop (VDCR arm)

VDCR; VDR

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Millennium Pharmaceuticals, Inc.: lead
• Johnson & Johnson Pharmaceutical Research & Development, L.L.C.: collaborator

Study Sites (2)

Rocky Mountain Cancer Center

Denver, Colorado, 80218, United States

Location

Mayo Clinic

Rochester, Minnesota, 55904-0001, United States

Location

Related Publications (2)

• 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.

  PMID: 22422823 DERIVED

• 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.

  PMID: 20508619 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bortezomib; Dexamethasone; Cyclophosphamide; Lenalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dixie-Lee Esseltine, MD
• Organization: Millennium Pharmaceuticals, Inc

(617) 679-7000

Study Officials

• Medical Monitor

  Millennium Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 25, 2007
• First Posted: July 26, 2007
• Study Start: August 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: November 1, 2010
• Last Updated: July 26, 2013
• Results First Posted: December 29, 2011

Record last verified: 2012-04

Locations

US (2)