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Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65 (DFCI 10-106)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Dana-Farber Cancer Institute
Sponsor:
Collaborators:
Celgene Corporation
Millennium Pharmaceuticals, Inc.
Massachusetts General Hospital
Cape Cod Healthcare
Beth Israel Deaconess Medical Center
Emory University
University of Michigan
Fox Chase Cancer Center
Memorial Sloan-Kettering Cancer Center
Fred Hutchinson Cancer Research Center
Barbara Ann Karmanos Cancer Institute
Duke University
University of California, San Francisco
University of Chicago
M.D. Anderson Cancer Center
UNC Lineberger Comprehensive Cancer Center
Roswell Park Cancer Institute
Stanford University
University of Mississippi Medical Center
Mount Sinai School of Medicine
Wake Forest Baptist Health
University of Arizona
OHSU Knight Cancer Institute
Eastern Maine Medical Center
University of California, San Diego
University of Alabama at Birmingham
University of Pittsburgh
Ochsner Health System
University of Texas Southwestern Medical Center
State University of New York - Downstate Medical Center
Newton-Wellesley Hospital
Baylor College of Medicine
Beckman Research Institute
University of Florida
North Shore Long Island Jewish Health System
H. Lee Moffitt Cancer Center and Research Institute
Vanderbilt University
Ohio State University
Huntsman Cancer Institute
Columbia University
Information provided by (Responsible Party):
Paul G. Richardson, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT01208662
First received: September 23, 2010
Last updated: August 15, 2014
Last verified: August 2014
  Purpose

The drugs, lenalidomide, bortezomib, and dexamethasone, are approved by the FDA. They have not been approved in the combination for multiple myeloma or any other type of cancer. Bortezomib is currently approved by the FDA for the treatment of multiple myeloma. Lenalidomide is approved for use with dexamethasone for patients with multiple myeloma who have received at least one prior therapy and for the treatment of certain types of myelodysplastic syndrome (another type of cancer affecting the blood). Dexamethasone is commonly used, either alone, or in combination with other drugs, to treat multiple myeloma. Please note that Bortezomib and Lenalidomide are provided to patients participating in this trial at no charge. Melphalan and cyclophosphamide, the drugs used during stem cell collection and transplant, are also approved by the FDA. Melphalan is an FDA-approved chemotherapy for multiple myeloma and is used as a high-dose conditioning treatment prior to stem cell transplantation. Cyclophosphamide is used, either alone, or in combination with other drugs, to treat multiple myeloma. These drugs have been used in other multiple myeloma studies and information from those studies suggests that this combination of therapy may help to treat newly diagnosed multiple myeloma.

In this research study, we are looking to explore the drug combination, lenalidomide, bortezomib and dexamethasone alone or when combined with autologous stem cell transplantation to see what side effects it may have and how well it works for treatment of newly diagnosed multiple myeloma. Specifically, the objective of this trial is to determine if, in the era of novel drugs, high dose therapy (HDT) is still necessary in the initial management of multiple myeloma in younger patients. In this study, HDT as compared to conventional dose treatment would be considered superior if it significantly prolongs progression-free survival by at least 9 months or more, recognizing that particular subgroups may benefit more compared to others.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Drug: Bortezomib
Drug: Dexamethasone
Procedure: Autologous Stem Cell Transplant
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Phase III Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib, and Dexamethasone (RVD) to High-Dose Treatment With Peripheral Stem Cell Transplant in the Initial Management of Myeloma in Patients Up to 65 Years of Age

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • Primary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To compare progression-free survival (PFS) between Arm A and Arm B.


Secondary Outcome Measures:
  • Secondary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To compare the response rates (RR) between the two arms.

  • Secondary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To compare time to progression (TTP) between the two arms.

  • Secondary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To compare the overall survival (OS) between the two arms.

  • Secondary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: Yes ]
    To compare toxicity between the two arms.

  • Secondary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To define genetic prognostic groups evaluated by gene expression profiling (GEP).

  • Secondary Outcomes [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To examine the best treatment in each GEP-defined prognostic group.

  • Secondary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To compare quality of life (QOL) between the two arms.

  • Secondary Outcome [ Time Frame: Up to 6 years or until progression ] [ Designated as safety issue: No ]
    To collect medical resource utilization (MRU) information which may be used in economic evaluation models.


Estimated Enrollment: 660
Study Start Date: September 2010
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: High Dose Treatment
Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Maintenance Lenalidomide.
Drug: Lenalidomide

Oral, 25 mg/day, days 1-14 for 8 total cycles for Arm A. Oral, 25 mg/day, days 1-14 for 5 total cycles for Arm B.

Oral, 10-15 mg/day, daily for 12 months in maintenance for Arm A and Arm B.

Other Name: CC-5013
Drug: Bortezomib
IV, days 1, 4, 8 and 11 for 8 total cycles for Arm A. IV, days 1, 4, 8 and 11 for 5 total cycles for Arm B.
Other Names:
  • PS-341
  • Velcade
Drug: Dexamethasone

Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 8 total cycles for Arm A. Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 5 total cycles for Arm B.

Dose of 20 mg/day for first 3 cycles. Dose of 10 mg/day for remaining cycles.

Other Name: Decadron
Experimental: High Dose Treatment with SCT
Lenalidomide, bortezomib, dexamethasone. Stem cell collection. Autologous Stem Cell Transplant. Maintenance Lenalidomide.
Drug: Lenalidomide

Oral, 25 mg/day, days 1-14 for 8 total cycles for Arm A. Oral, 25 mg/day, days 1-14 for 5 total cycles for Arm B.

Oral, 10-15 mg/day, daily for 12 months in maintenance for Arm A and Arm B.

Other Name: CC-5013
Drug: Bortezomib
IV, days 1, 4, 8 and 11 for 8 total cycles for Arm A. IV, days 1, 4, 8 and 11 for 5 total cycles for Arm B.
Other Names:
  • PS-341
  • Velcade
Drug: Dexamethasone

Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 8 total cycles for Arm A. Oral, days 1, 2, 4, 5, 8, 9, 11 and 12 for 5 total cycles for Arm B.

Dose of 20 mg/day for first 3 cycles. Dose of 10 mg/day for remaining cycles.

Other Name: Decadron
Procedure: Autologous Stem Cell Transplant
Stem cell transplant

Detailed Description:

After screening procedures determine if a patient is eligible for this research study, the patient will be randomized into one of the study groups: lenalidomide, bortezomib and dexamethasone without autologous stem cell transplantation, followed by lenalidomide maintenance (Arm A) or lenalidomide, bortezomib and dexamethasone with autologous stem cell transplantation, followed by lenalidomide maintenance (Arm B). There is an equal chance of being placed in either group.

All participants will receive one cycle of lenalidomide, bortezomib and dexamethasone treatment before being randomized to Arm A or Arm B.

Participants in Arm A will receive two additional cycles of lenalidomide, bortezomib and dexamethasone prior to stem cell collection. If randomized to Arm A, the subject will undergo stem cell collection, followed by five cycles of lenalidomide, bortezomib and dexamethasone. This will be followed by lenalidomide maintenance treatment until disease progression.

Participants in Arm B will receive two additional cycles of lenalidomide, bortezomib and dexamethasone prior to stem cell collection. If randomized to Arm B, the subject will undergo stem cell collection and autologous stem cell transplantation, followed by two cycles of lenalidomide, bortezomib and dexamethasone. This will be followed by lenalidomide maintenance treatment until disease progression.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Multiple Myeloma, according to the International Myeloma Foundation 2003 Diagnostic Criteria
  • Documented symptomatic myeloma, with organ damage related to myeloma with laboratory assessments performed within 21 days of registration
  • Myeloma that is measurable by either serum or urine evaluation of the monoclonal component or by assay of serum free light chains.
  • ECOG performance status </= 2
  • Negative HIV blood test
  • Voluntary written informed consent

Exclusion Criteria:

  • Pregnant or lactating female
  • Prior systemic therapy for MM (localized radiotherapy allowed if at least 7 days before study entry, corticosteroids allowed if dose </= equivalent of 160 mg dexamethasone over 2 weeks)
  • Primary amyloidosis (AL) or myeloma complicated by amylosis
  • Receiving any other investigational agents
  • Known brain metastases
  • Poor tolerability or allergy to any of the study drugs or compounds of similar composition
  • Platelet count <50,000/mm3, within 21 days of registration
  • ANC <1,000 cells/mm3, within 21 days of registration
  • Hemoglobin <8 g/dL, within 21 days of registration
  • Hepatic impairment (>/= 1.5 x institutional ULN or AST (SGOT), ALT (SGPT), or alkaline phosphatase >2 x ULN). Patients with benign hyperbilirubinemia are eligible.
  • Renal insufficiency (serum creatinine >2.0 mg/dl or creatinine clearance <50 ml/min, within 21 days of registration)
  • Respiratory compromise (DLCO < 50%)
  • Clinical signs of heart or coronary failure or LVEF < 40%. Myocardial infarction within 6 months prior to enrollment, NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conductive system abnormalities
  • Intercurrent illness including, but not limited to ongoing or active severe infection, known infection with hepatitis B or C virus, poorly controlled diabetes, severe uncontrolled psychiatric disorder or psychiatric illness/social situations that would limit compliance with study requirements
  • Previous history of another malignant condition except for basal cell carcinoma and stage I cervical cancer. If malignancy was experienced more than 2 years ago and confirmed as cured, these participants may be considered for the study on case by case basis with PI discussion.
  • Inability to comply with an anti-thrombotic treatment regimen
  • Peripheral neuropathy >/= Grade 2
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01208662

Contacts
Contact: Paul G Richardson, MD 617-632-2104 paul_richardson@dfci.harvard.edu

  Show 49 Study Locations
Sponsors and Collaborators
Paul G. Richardson, MD
Celgene Corporation
Millennium Pharmaceuticals, Inc.
Massachusetts General Hospital
Cape Cod Healthcare
Beth Israel Deaconess Medical Center
Emory University
University of Michigan
Fox Chase Cancer Center
Memorial Sloan-Kettering Cancer Center
Fred Hutchinson Cancer Research Center
Barbara Ann Karmanos Cancer Institute
Duke University
University of California, San Francisco
University of Chicago
M.D. Anderson Cancer Center
UNC Lineberger Comprehensive Cancer Center
Roswell Park Cancer Institute
Stanford University
University of Mississippi Medical Center
Mount Sinai School of Medicine
Wake Forest Baptist Health
University of Arizona
OHSU Knight Cancer Institute
Eastern Maine Medical Center
University of California, San Diego
University of Alabama at Birmingham
University of Pittsburgh
Ochsner Health System
University of Texas Southwestern Medical Center
State University of New York - Downstate Medical Center
Newton-Wellesley Hospital
Baylor College of Medicine
Beckman Research Institute
University of Florida
North Shore Long Island Jewish Health System
H. Lee Moffitt Cancer Center and Research Institute
Vanderbilt University
Ohio State University
Huntsman Cancer Institute
Columbia University
Investigators
Principal Investigator: Paul G. Richardson, MD Dana-Farber Cancer Institute
  More Information

No publications provided

Responsible Party: Paul G. Richardson, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT01208662     History of Changes
Other Study ID Numbers: 10-106
Study First Received: September 23, 2010
Last Updated: August 15, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dana-Farber Cancer Institute:
Lenalidomide
Bortezomib
Dexamethasone
Stem Cell Transplant
Myeloma
Multiple Myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents

ClinicalTrials.gov processed this record on November 24, 2014