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

Sponsor
Paul G. Richardson, MD (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01208662
Collaborator
Celgene Corporation (Industry), Millennium Pharmaceuticals, Inc. (Industry), Massachusetts General Hospital (Other), Cape Cod Hospital (Other), Beth Israel Deaconess Medical Center (Other), Emory University (Other), University of Michigan (Other), Fox Chase Cancer Center (Other), Memorial Sloan Kettering Cancer Center (Other), Fred Hutchinson Cancer Research Center (Other), Barbara Ann Karmanos Cancer Institute (Other), Duke University (Other), University of California, San Francisco (Other), University of Chicago (Other), M.D. Anderson Cancer Center (Other), UNC Lineberger Comprehensive Cancer Center (Other), Roswell Park Cancer Institute (Other), Stanford University (Other), University of Mississippi Medical Center (Other), Icahn School of Medicine at Mount Sinai (Other), Wake Forest University Health Sciences (Other), University of Arizona (Other), OHSU Knight Cancer Institute (Other), Eastern Maine Medical Center (Other), University of California, San Diego (Other), University of Alabama at Birmingham (Other), University of Pittsburgh Medical Center (Other), Ochsner Health System (Other), University of Texas Southwestern Medical Center (Other), State University of New York - Downstate Medical Center (Other), Newton-Wellesley Hospital (Other), Baylor College of Medicine (Other), City of Hope Medical Center (Other), University of Florida (Other), Northwell Health (Other), H. Lee Moffitt Cancer Center and Research Institute (Other), Vanderbilt University Medical Center (Other), Ohio State University (Other), Huntsman Cancer Institute (Other), Columbia University (Other)
660
Enrollment
46
Locations
2
Arms
164
Duration (Months)
14.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 or DiseaseIntervention/TreatmentPhase
Phase 3

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
660 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (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
Study Start Date :
Jan 1, 2010
Anticipated Primary Completion Date :
Feb 1, 2022
Anticipated Study Completion Date :
Sep 1, 2023

Arms and Interventions

ArmIntervention/Treatment
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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Decadron
  • Procedure: Autologous Stem Cell Transplant
    Stem cell transplant

    Outcome Measures

    Primary Outcome Measures

    1. Primary Outcome [Up to 6 years or until progression]

      To compare progression-free survival (PFS) between Arm A and Arm B.

    Secondary Outcome Measures

    1. Secondary Outcome [Up to 6 years or until progression]

      To compare the response rates (RR) between the two arms.

    2. Secondary Outcome [Up to 6 years or until progression]

      To compare time to progression (TTP) between the two arms.

    3. Secondary Outcome [Up to 6 years or until progression]

      To compare the overall survival (OS) between the two arms.

    4. Secondary Outcome [Up to 6 years or until progression]

      To compare toxicity between the two arms.

    5. Secondary Outcome [Up to 6 years or until progression]

      To define genetic prognostic groups evaluated by gene expression profiling (GEP).

    6. Secondary Outcomes [Up to 6 years or until progression]

      To examine the best treatment in each GEP-defined prognostic group.

    7. Secondary Outcome [Up to 6 years or until progression]

      To compare quality of life (QOL) between the two arms.

    8. Secondary Outcome [Up to 6 years or until progression]

      To collect medical resource utilization (MRU) information which may be used in economic evaluation models.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35294
    2Arizona Comprehensive Cancer CenterTucsonArizonaUnited States85724
    3City of HopeDuarteCaliforniaUnited States91010
    4University of California at San DiegoLa JollaCaliforniaUnited States
    5University of California, San FranciscoSan FranciscoCaliforniaUnited States94143
    6Stanford UniversityStanfordCaliforniaUnited States94305
    7Colorado Blood Cancer InstituteDenverColoradoUnited States80218
    8University of FloridaGainesvilleFloridaUnited States32608
    9H. Lee Moffitt Cancer CenterTampaFloridaUnited States33612
    10Emory UniversityAtlantaGeorgiaUnited States30322
    11Mountain States Tumor Institute at St. Luke's Regional Medical CenterBoiseIdahoUnited States83712
    12University of ChicagoChicagoIllinoisUnited States60637
    13Ochsner Foundation ClinicNew OrleansLouisianaUnited States70121
    14Eastern Maine Medical CenterBrewerMaineUnited States04412
    15Massachusetts General HospitalBostonMassachusettsUnited States02114
    16Dana-Farber Cancer InstituteBostonMassachusettsUnited States02115
    17Beth Israel Deaconess Medical CenterBostonMassachusettsUnited States02215
    18Cape Cod HealthcareHyannisMassachusettsUnited States02601
    19Newton-Wellesley HospitalNewtonMassachusettsUnited States
    20University of MichiganAnn ArborMichiganUnited States48109
    21Barbara Ann Karmanos Cancer InstituteDetroitMichiganUnited States48201
    22University of Mississippi Medical CenterJacksonMississippiUnited States39216
    23New Hampshire Oncology and HematologyConcordNew HampshireUnited States
    24New Hampshire Oncology and HematologyHooksettNew HampshireUnited States
    25New Hampshire Oncology and HematologyLaconiaNew HampshireUnited States
    26State University of New York Downstate Medical CenterBrooklynNew YorkUnited States
    27Roswell Park Cancer InstituteBuffaloNew YorkUnited States14263
    28North Shore Long Island Jewish Health SystemLake SuccessNew YorkUnited States11042
    29Memorial Sloan Kettering Cancer CenterNew YorkNew YorkUnited States10021
    30Mount Sinai Medical CenterNew YorkNew YorkUnited States10029
    31Columbia UniversityNew YorkNew YorkUnited States10032
    32University of Rochester Medical CenterRochesterNew YorkUnited States14642
    33UNC Lineberger Comprehensive Cancer CenterChapel HillNorth CarolinaUnited States27599
    34Duke UniversityDurhamNorth CarolinaUnited States27710
    35Wake Forest UniversityWinston-SalemNorth CarolinaUnited States27157
    36Ohio State University Medical CenterColumbusOhioUnited States43210
    37Oregon Health and SciencesPortlandOregonUnited States
    38University of Pennsylvania Medical CenterPhiladelphiaPennsylvaniaUnited States19104
    39Fox Chase Cancer CenterPhiladelphiaPennsylvaniaUnited States19111
    40University of Pittsburgh Medical CenterPittsburghPennsylvaniaUnited States15232
    41Vanderbilt UniversityNashvilleTennesseeUnited States37203
    42University of Texas Southwestern Medical CenterDallasTexasUnited States75390
    43Baylor College of MedicineHoustonTexasUnited States77030
    44MD Anderson Cancer CenterHoustonTexasUnited States77030
    45Huntsman Cancer InstituteSalt Lake CityUtahUnited States
    46Fred Hutchinson Cancer Research CenterSeattleWashingtonUnited States98109

    Sponsors and Collaborators

    • Paul G. Richardson, MD
    • Celgene Corporation
    • Millennium Pharmaceuticals, Inc.
    • Massachusetts General Hospital
    • Cape Cod Hospital
    • 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
    • Icahn School of Medicine at Mount Sinai
    • Wake Forest University Health Sciences
    • University of Arizona
    • OHSU Knight Cancer Institute
    • Eastern Maine Medical Center
    • University of California, San Diego
    • University of Alabama at Birmingham
    • University of Pittsburgh Medical Center
    • Ochsner Health System
    • University of Texas Southwestern Medical Center
    • State University of New York - Downstate Medical Center
    • Newton-Wellesley Hospital
    • Baylor College of Medicine
    • City of Hope Medical Center
    • University of Florida
    • Northwell Health
    • H. Lee Moffitt Cancer Center and Research Institute
    • Vanderbilt University Medical Center
    • Ohio State University
    • Huntsman Cancer Institute
    • Columbia University

    Investigators

    • Principal Investigator: Paul G. Richardson, MD, Dana-Farber Cancer Institute

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Paul G. Richardson, MD, Principal Investigator, Dana-Farber Cancer Institute
    ClinicalTrials.gov Identifier:
    NCT01208662
    Other Study ID Numbers:
    • 10-106
    First Posted:
    Sep 24, 2010
    Last Update Posted:
    Oct 7, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by Paul G. Richardson, MD, Principal Investigator, Dana-Farber Cancer Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 7, 2021