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 (Responsible Party):	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:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
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: End of treatment period ] [ Designated as safety issue: No ]
Complete response requires egative 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

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 ]

Enrollment:	172
Study Start Date:	August 2007
Study Completion Date:	November 2010
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: VDR 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.
Experimental: VDCR 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.
Experimental: VDC 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.
Experimental: VDC-mod 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.
ClinicalTrials.gov Identifier:	NCT00507442 History of Changes
Other Study ID Numbers:	C05008
Study First Received:	July 25, 2007
Results First Received:	November 28, 2011
Last Updated:	November 28, 2011
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:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide

Thalidomide
Bortezomib
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on February 12, 2012