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

NCT01208662 | Active Not Recruiting Phase 3 Results DMC

• 1 other identifier: 10-106
• Study Type: interventional
• Target: 729
• Locations: 1 country
• Sites: 46

Brief Summary

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.

Conditions

Multiple Myeloma

Keywords

Lenalidomide; Bortezomib; Dexamethasone; Stem Cell Transplant; Myeloma; Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Median Progression-Free Survival (PFS)

  PFS was estimated using the Kaplan-Meier (KM) method and defined as time from randomization to the earlier of disease progression (PD) as determined by central review or death from any cause (events). Patients who started non-protocol therapy (NPT) were censored at the date of NPT initiation if available or date treatment ended if date of NPT was missing. Deaths occurring beyond 1 year from the date last known progression-free are not counted as events and censored at date of last disease evaluation. Patients who had not started NPT, progressed, or died were censored at the date of last disease evaluation. PD was based upon the International Myeloma Working Group (IMWG) uniform response criteria. \[Kumar S, et al Lancet Oncol 2016;17(8):e328-e346\].

  On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median (maximum) PFS follow-up was 70 and 129 months.

Secondary Outcomes (14)

• Partial Response (PR) Rate

  Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 133.5 months in this study cohort.

• Very Good Partial Response (VGPR) Rate

  Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 134 months in this study cohort.

• Complete Response (CR) Rate

  Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 134 months in this study cohort.

• Median Duration of Response: Partial Response (DOR PR)

  On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median (maximum) DOR PR follow-up was 62.9 and 122.9 months.

• 5-Year Time to Progression (TTP)

  On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median TTP follow-up was 70 months. The probability estimate is at 5 years.

Study Arms (2)

RVD Alone

EXPERIMENTAL

All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12

Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone

RVD plus ASCT

ACTIVE COMPARATOR

All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (\~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12

Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone; Procedure: Autologous Stem Cell Transplant

Interventions

Lenalidomide DRUG

oral administration

Also known as: CC-5013

RVD Alone; RVD plus ASCT

Bortezomib DRUG

intravenous or, following protocol amendment, subcutaneous administration

Also known as: PS-341, Velcade

RVD Alone; RVD plus ASCT

Dexamethasone DRUG

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

Also known as: Decadron

RVD Alone; RVD plus ASCT

Autologous Stem Cell Transplant PROCEDURE

Autologous refers to stem cells that are harvested from the participant to be a source of new blood cells after high-dose chemotherapy with melphalan.

Also known as: Peripheral Blood Stem Cell (PBSC) Transplant

RVD plus ASCT

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Paul Richardson, MD: lead
• Celgene Corporation: collaborator
• Millennium Pharmaceuticals, Inc.: collaborator
• Massachusetts General Hospital: collaborator
• Cape Cod Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Emory University: collaborator
• University of Michigan: collaborator
• Fox Chase Cancer Center: collaborator
• Memorial Sloan Kettering Cancer Center: collaborator
• Fred Hutchinson Cancer Center: collaborator
• Barbara Ann Karmanos Cancer Institute: collaborator
• Duke University: collaborator
• University of California, San Francisco: collaborator
• University of Chicago: collaborator
• M.D. Anderson Cancer Center: collaborator
• UNC Lineberger Comprehensive Cancer Center: collaborator
• Roswell Park Cancer Institute: collaborator
• Stanford University: collaborator
• University of Mississippi Medical Center: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• Wake Forest University Health Sciences: collaborator
• University of Arizona: collaborator
• OHSU Knight Cancer Institute: collaborator
• Eastern Maine Medical Center: collaborator
• University of California, San Diego: collaborator
• University of Alabama at Birmingham: collaborator
• University of Pittsburgh Medical Center: collaborator
• Ochsner Health System: collaborator
• State University of New York - Downstate Medical Center: collaborator
• Newton-Wellesley Hospital: collaborator
• Baylor College of Medicine: collaborator
• City of Hope Medical Center: collaborator
• University of Florida: collaborator
• Northwell Health: collaborator
• H. Lee Moffitt Cancer Center and Research Institute: collaborator
• Vanderbilt University Medical Center: collaborator
• Ohio State University: collaborator
• Huntsman Cancer Institute: collaborator
• Columbia University: collaborator
• University of Texas Southwestern Medical Center: collaborator

Study Sites (46)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Arizona Comprehensive Cancer Center

Tucson, Arizona, 85724, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California at San Diego

La Jolla, California, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Stanford University

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Mountain States Tumor Institute at St. Luke's Regional Medical Center

Boise, Idaho, 83712, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Ochsner Foundation Clinic

New Orleans, Louisiana, 70121, United States

Location

Eastern Maine Medical Center

Brewer, Maine, 04412, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Cape Cod Healthcare

Hyannis, Massachusetts, 02601, United States

Location

Newton-Wellesley Hospital

Newton, Massachusetts, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

New Hampshire Oncology and Hematology

Concord, New Hampshire, United States

Location

New Hampshire Oncology and Hematology

Hooksett, New Hampshire, United States

Location

New Hampshire Oncology and Hematology

Laconia, New Hampshire, United States

Location

State University of New York Downstate Medical Center

Brooklyn, New York, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

North Shore Long Island Jewish Health System

Lake Success, New York, 11042, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

Oregon Health and Sciences

Portland, Oregon, United States

Location

University of Pennsylvania Medical Center

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Vanderbilt University

Nashville, Tennessee, 37203, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. doi: 10.1056/NEJMoa2204925. Epub 2022 Jun 5.

  PMID: 35660812 RESULT

• Parmar H, Vesole DH, Biran N. From VAD to VRD: Is Transplant Still Needed in the Upfront Setting of Myeloma? Cancer J. 2021 May-Jun 01;27(3):190-195. doi: 10.1097/PPO.0000000000000522.

  PMID: 34549906 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Lenalidomide; Bortezomib; Dexamethasone; Calcium Dobesilate; Transplantation

Condition Hierarchy (Ancestors)

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Surgical Procedures, Operative

Results Point of Contact

• Title: Ajantha Nithi
• Organization: Dana-Farber Cancer Institute

ajantha_nithi@dfci.harvard.edu

857-215-2829

Study Officials

• Paul G. Richardson, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 24, 2010
• Study Start: September 1, 2010
• Primary Completion: February 1, 2022
• Study Completion (Estimated): December 1, 2026
• Last Updated: January 22, 2026
• Results First Posted: December 18, 2023

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (46)