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

Sponsor:	Millennium Pharmaceuticals, Inc.
Collaborator:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Information provided by:	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00507442

Purpose

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 CR/ very good partial response (VGPR) rate.

Condition	Intervention	Phase
Multiple Myeloma	Drug: bortezomib + dexamethasone + lenalidomide Drug: bortezomib + dexamethasone + cyclophosphamide + lenalidomide Drug: bortezomib + dexamethasone + cyclophosphamide Drug: Bortezomib + Dexamethasone + Cyclophosphamide	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Phase 1/2 Study of VELCADE®, Dexamethasone, and Revlimid® Versus VELCADE, Dexamethasone, Cyclophosphamide, and Revlimid Versus VELCADE, Dexamethasone and Cyclophosphamide in Subjects With Previously Untreated Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Dexamethasone Cyclophosphamide Dexamethasone acetate Doxiproct plus Bortezomib Lenalidomide CC 5013 Dexamethasone Sodium Phosphate

U.S. FDA Resources

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:

Combined complete response and very good partial response. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Evaluate the safety and tolerability of the combination therapy [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
Overall Response [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Stringent Complete Response Rate [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Complete Response Rate + Near Complete Response Rate [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Duration of Response [ Time Frame: time from date of first documented confirmed response to date of first documented progressive disease ] [ Designated as safety issue: No ]
Time to Disease Progression [ Time Frame: time from date of randomization to date of first documented progressive disease ] [ Designated as safety issue: No ]
Time to Response [ Time Frame: time from date of randomization to the date of the first documentation of a confirmed response ] [ Designated as safety issue: No ]
Progression-free Survival [ Time Frame: time from the date of randomization to the date of the first documented progressive disease or death. ] [ Designated as safety issue: No ]
1-year Survival [ Time Frame: survival probability at 1 year after randomization ] [ Designated as safety issue: No ]
Overall Survival [ Time Frame: time from the date of randomization to the date of death ] [ Designated as safety issue: No ]

Estimated Enrollment:	157
Study Start Date:	August 2007
Estimated Study Completion Date:	September 2010
Estimated Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
VDR: Experimental bortezomib, dexamethasone, and lenalidomide	Drug: bortezomib + dexamethasone + lenalidomide bortezomib 1.3 mg/m2 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). dexamethasone 40mg orally on days 1,8, and 15 of a 3-week cycle for 8 cycles, then stop. lenalidomide 25mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop.
VDCR: Experimental Bortezomib, Dexamethasone, Cyclophosphamide, Lenalidomide	Drug: bortezomib + dexamethasone + cyclophosphamide + lenalidomide bortezomib 1.3 mg/m2 intravenously 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). dexamethasone 40mg orally on days 1,8, and 15 of a 3-week cycle for 8 cycles, then stop. cyclophosphamide 500mg/m2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop. lenalidomide 15mg orally on days 1 to 14 of a 3-week cycle for 8 cycles then stop.
VDC: Experimental Bortezomib, Dexamethasone, Cyclophosphamide	Drug: bortezomib + dexamethasone + cyclophosphamide bortezomib 1.3 mg/m2 intravenously 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). dexamethasone 40mg orally on days 1,8, and 15 of a 3-week cycle for 8 cycles, then stop. cyclophosphamide 500mg/m2 orally on days 1 and 8 of a 3-week cycle for 8 cycles, then stop.
VDC-mod: Experimental Modified dosing of Bortezomib, Dexamethasone and Cyclophosphamide	Drug: Bortezomib + Dexamethasone + Cyclophosphamide bortezomib 1.3 mg/m2 intravenously 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). dexamethasone 40mg orally on days 1, 8 and 15 of a 3-week cycle for 8 cycles, then stop. cyclophosphamide 500mg/m2 orally on days 1, 8 and 15 of a 3-week cycle for 8 cycles, then stop.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00507442

Locations

United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55904-0001

Sponsors and Collaborators

Millennium Pharmaceuticals, Inc.

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

Study Director:

Medical Monitor

Millennium Pharmaceuticals, Inc.

More Information

No publications provided

Responsible Party:	Millennium Pharmaceuticals, Inc. ( Clinical Study Medical Monitor )
Study ID Numbers:	C05008
Study First Received:	July 25, 2007
Last Updated:	December 2, 2009
ClinicalTrials.gov Identifier:	NCT00507442 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:

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

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Dexamethasone
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Blood Protein Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Paraproteinemias
Cyclophosphamide
Hemostatic Disorders
Hormones
Hemorrhagic Disorders
Therapeutic Uses

Cardiovascular Diseases
Alkylating Agents
Dexamethasone acetate
Immunoproliferative Disorders
Neoplasms by Histologic Type
Antineoplastic Agents, Hormonal
Immune System Diseases
Hematologic Diseases
Bortezomib
Gastrointestinal Agents
Vascular Diseases
Lenalidomide
Enzyme Inhibitors
Glucocorticoids
Immunosuppressive Agents

ClinicalTrials.gov processed this record on February 08, 2010