NCT01109004

Brief Summary

The study is designed as a Phase III, multicenter trial of tandem autologous transplants plus maintenance therapy versus the strategy of single autologous transplant plus consolidation therapy with lenalidomide, bortezomib and dexamethasone (RVD) followed by maintenance therapy or single autologous transplant plus maintenance therapy as part of upfront treatment of multiple myeloma (MM). Lenalidomide will be used as maintenance therapy for three years in all arms.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
758

participants targeted

Target at P75+ for phase_3 multiple-myeloma

Timeline
Completed

Started May 2010

Typical duration for phase_3 multiple-myeloma

Geographic Reach
1 country

54 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 21, 2010

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 22, 2010

Completed
9 days until next milestone

Study Start

First participant enrolled

May 1, 2010

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 15, 2017

Completed
1.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 3, 2018

Completed
3 months until next milestone

Results Posted

Study results publicly available

June 11, 2018

Completed
Last Updated

December 9, 2021

Status Verified

December 1, 2021

Enrollment Period

6.7 years

First QC Date

April 21, 2010

Results QC Date

April 5, 2018

Last Update Submit

December 8, 2021

Conditions

Keywords

Symptomatic Multiple MyelomaLenalidomideAnti-Myeloma AgentsHematologic DisordersMaintenance TherapyProgressionAutologous TransplantRVD Consolidation

Outcome Measures

Primary Outcomes (1)

  • Percentage of Participants With Progression-free Survival (PFS)

    Progression-free survival is defined as survival without disease progression or initiation of non-protocol anti-myeloma therapy. To account for loss to follow-up of a few participants, the Kaplan-Meier estimator was used to estimate progression-free survival at 38 months post-randomization.

    38 months post-randomization

Secondary Outcomes (9)

  • Percentage of Participants With Disease Progression

    38 months post-randomization

  • Percentage of Participants With Overall Survival (OS)

    38 months post-randomization

  • Percentage of Participants With Treatment-related Mortality (TRM)

    Up to 38 months post-randomization

  • Number of Participants With Treatment Response

    1 and 2 years post-randomization

  • FACT-G Total Score

    Up to 3 years post-randomization

  • +4 more secondary outcomes

Study Arms (3)

Tandem auto transplant

ACTIVE COMPARATOR

Initial autologous transplant followed by a second autologous transplant and lenalidomide maintenance

Drug: Lenalidomide

RVD consolidation

ACTIVE COMPARATOR

Initial autologous transplant followed by lenalidomide, bortezomib and dexamethasone (RVD) consolidation and lenalidomide maintenance

Drug: lenalidomide, bortezomib and dexamethasone

Lenalidomide maintenance

ACTIVE COMPARATOR

Initial autologous transplant followed by lenalidomide maintenance

Drug: Lenalidomide

Interventions

All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive a second autologous PBSC transplant with the same conditioning regimen as the first transplant. All patients will also receive maintenance lenalidomide which will start after the second transplant. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Also known as: Revlimidâ„¢
Tandem auto transplant

All patients will undergo a first autologous peripheral blood stem cell (PBSC) transplant with high-dose melphalan (200 mg/m\^2 IV) given on Day -2. Upon recovery from the first transplant patients will receive consolidation therapy with RVD (lenalidomide 15 mg/day on Days 1-14, dexamethasone 40mg on Days 1, 8 and 15, and bortezomib 1.3mg/m2 on Days 1, 4, 8 and 11 of every 21 day cycle, patients will receive four cycles). All patients will also receive maintenance lenalidomide which will start after consolidation therapy. Maintenance therapy with lenalidomide will start at 10 mg daily for 3 months and increase to 15 mg daily. The duration of maintenance will be three years in all treatment arms.

Also known as: Revlimid™, Velcade®, and Decadron
RVD consolidation

Eligibility Criteria

AgeUp to 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Patients meeting the criteria for symptomatic multiple myeloma (MM).
  • Patients who are 70 years of age, or younger, at time of enrollment.
  • Patients who have received at least two cycles of any regimen as initial systemic therapy and are within 2 - 12 months of the first dose of initial therapy.
  • Cardiac function: left ventricular ejection fraction at rest greater than 40 percent.
  • Hepatic: bilirubin less than 1.5x the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 2.5x the upper limit of normal. (Patients who have been diagnosed with Gilbert's Disease are allowed to exceed the defined bilirubin value of 1.5x the upper limit of normal.)
  • Renal: Creatinine clearance of grater than or equal to 40 mL/min, estimated or calculated.
  • Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50 percent of predicted value (corrected for hemoglobin).
  • Patients with an adequate autologous graft defined as a cryopreserved PBSC graft containing greater than or equal to 4 x 10\^6 CD34+ cells/kg patient weight. The graft may not be CD34+ selected or otherwise manipulated to remove tumor or other cells. The graft can be collected at the transplanting institution or by a referring center. The autograft must be stored so that there are two products each containing at least 2 x 10\^6 CD34+ cells/kg patient weight.
  • Signed informed consent form.

You may not qualify if:

  • Patients who never fulfill the criteria for symptomatic MM.
  • Patients with purely non-secretory MM \[absence of a monoclonal protein (M protein) in serum as measured by electrophoresis and immunofixation and the absence of Bence Jones protein in the urine defined by use of conventional electrophoresis and immunofixation techniques\]. Patients with light chain MM detected in the serum by free light chain assay are eligible.
  • Patients with plasma cell leukemia.
  • Karnofsky performance score less than 70 percent.
  • Patients with greater than grade 2 sensory neuropathy (CTCAE).
  • Patients with uncontrolled bacterial, viral or fungal infections (currently taking medication and progression of clinical symptoms).
  • Patients seropositive for the human immunodeficiency virus (HIV).
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant.
  • Patient has hypersensitivity to bortezomib, boron or mannitol.
  • Patient has received other investigational drugs with 14 days before enrollment.
  • Patients with prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs. Cancer treated with curative intent greater than 5 years previously is allowed.
  • Female patients who are pregnant (positive B-HCG) or breastfeeding.
  • Females of childbearing potential (FCBP) or men who have sexual contact with FCBP unwilling to use contraceptive techniques during the length of lenalidomide maintenance therapy.
  • Prior allograft or prior autograft.
  • Patients who have received mid-intensity melphalan (greater than 50 mg IV) as part of prior therapy.
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (54)

Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

UCSD Medical Center

La Jolla, California, 92093, United States

Location

University of California, San Francisco

San Francisco, California, 94143-0324, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Christiana Care Health System

Newark, Delaware, 19718, United States

Location

University of Florida College of Medicine

Gainesville, Florida, 32610, United States

Location

Florida Hospital Cancer Institute

Orlando, Florida, 32804, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33624, United States

Location

Blood and Marrow Transplant Program at Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Georgia Health Sciences University

Augusta, Georgia, 30912, United States

Location

St. Lukes Mountain States Tumor Institute

Boise, Idaho, 83712, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Wichita CCOP

Wichita, Kansas, 67214, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Louisiana State University Health Sciences Center

Shreveport, Louisiana, 71130, United States

Location

DFCI, Brigham and Womens Hospital

Boston, Massachusetts, 02114, United States

Location

DFCI, Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48105-2967, United States

Location

Karmanos Cancer Institute/BMT

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University, Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-7680, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Center

Buffalo, New York, 14263, United States

Location

North Shore University Hospital

Lake Success, New York, 11042, United States

Location

Mount Sinai Medical Center

New York, New York, 10029, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10174, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University of North Carolina Hospital at Chapel Hill

Chapel Hill, North Carolina, 27599-7305, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

Location

Jewish Hospital BMT Program

Cincinnati, Ohio, 45236, United States

Location

University Hospitals of Cleveland

Cleveland, Ohio, 44106-5061, United States

Location

Ohio State/Arthur G. James Cancer Hospital

Columbus, Ohio, 43210, United States

Location

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239-3098, United States

Location

Penn State College of Medicine, The Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Thompson Cancer Survival Center

Knoxville, Tennessee, 37916, United States

Location

Sarah Cannon Blood & Marrow Transplant Program

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-8210, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine/The Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas, MD Anderson CRC

Houston, Texas, 77030, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

West Virginia University Hospital

Morgantown, West Virginia, 26506, United States

Location

University of Wisconsin Hospital & Clinics

Madison, Wisconsin, 53792-5156, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53211, United States

Location

Related Publications (2)

  • Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S, Efebera Y, Ganguly S, Gasparetto C, Geller N, Horowitz MM, Koreth J, Knust K, Landau H, Brunstein C, McCarthy P, Nelson C, Qazilbash MH, Shah N, Vesole DH, Vij R, Vogl DT, Giralt S, Somlo G, Krishnan A. Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma: Results of the BMT CTN 0702 Trial. J Clin Oncol. 2019 Mar 1;37(7):589-597. doi: 10.1200/JCO.18.00685. Epub 2019 Jan 17.

  • Pasquini MC, Wallace PK, Logan B, Kaur M, Tario JD, Howard A, Zhang Y, Brunstein C, Efebera Y, Geller N, Giralt S, Hari P, Horowitz MM, Koreth J, Krishnan A, Landau H, Somlo G, Shah N, Stadtmauer E, Vogl DT, Vesole DH, McCarthy PL, Hahn T. Minimal Residual Disease Status in Multiple Myeloma 1 Year After Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance Are Associated With Long-Term Overall Survival. J Clin Oncol. 2024 Aug 10;42(23):2757-2768. doi: 10.1200/JCO.23.00934. Epub 2024 May 3.

MeSH Terms

Conditions

Multiple MyelomaHematologic DiseasesDisease Progression

Interventions

LenalidomideBortezomibDexamethasoneCalcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingBoronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsPyrazinesPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsArylsulfonatesArylsulfonic AcidsSulfonic AcidsSulfur AcidsSulfur Compounds

Results Point of Contact

Title
Adam Mendizabal, PhD
Organization
The Emmes Corporation

Study Officials

  • Mary Horowitz, MD

    Center for International Blood and Marrow Transplant Research

    STUDY DIRECTOR

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
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 21, 2010

First Posted

April 22, 2010

Study Start

May 1, 2010

Primary Completion

January 15, 2017

Study Completion

March 3, 2018

Last Updated

December 9, 2021

Results First Posted

June 11, 2018

Record last verified: 2021-12

Data Sharing

IPD Sharing
Will share

Results will be published in a manuscript and supporting information submitted to NIH BioLINCC (including data dictionaries, case report forms, data submission documentation, documentation for outcomes dataset, etc where indicated).

Shared Documents
STUDY PROTOCOL, ICF
Time Frame
Within 6 months of official study closure at participating sites.
Access Criteria
Available to the public
More information

Locations