NCT00075829

Brief Summary

The study is designed as a Phase III, multi-center trial of tandem autologous transplants versus the strategy of autologous followed by Human Leukocyte Antigen (HLA)-matched sibling non-myeloablative allogeneic transplant. Study subjects will be biologically assigned to the appropriate arm depending on the availability of an HLA-matched sibling. There is a nested randomized phase III trial of observation versus maintenance therapy following the second autologous transplant for patients on the tandem autologous transplant arm.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
710

participants targeted

Target at P75+ for phase_3 multiple-myeloma

Timeline
Completed

Started Dec 2003

Longer than P75 for phase_3 multiple-myeloma

Geographic Reach
1 country

36 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

Study Start

First participant enrolled

December 1, 2003

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

January 9, 2004

Completed
4 days until next milestone

First Posted

Study publicly available on registry

January 13, 2004

Completed
8.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
3.4 years until next milestone

Results Posted

Study results publicly available

August 4, 2016

Completed
Last Updated

November 1, 2021

Status Verified

August 1, 2017

Enrollment Period

8.5 years

First QC Date

January 9, 2004

Results QC Date

December 17, 2014

Last Update Submit

October 19, 2021

Conditions

Keywords

Stage II Multiple MyelomaStage III Multiple MyelomaRefractory Plasma Cell Neoplasm

Outcome Measures

Primary Outcomes (1)

  • Progression-Free Survival (PFS)

    Patients are considered a failure for this endpoint if they die or if they progress or relapse.

    Year 3

Secondary Outcomes (7)

  • Overall Survival (OS) for Standard Risk

    Years 1, 2, and 3

  • Overall Survival (OS) for High Risk

    Year 3

  • Cumulative Incidence of Progression/Relapse

    Year 3

  • Cumulative Incidence of Treatment Related Mortality (TRM)

    Year 3

  • Interval From First to Second Transplantation

    Year 1

  • +2 more secondary outcomes

Study Arms (3)

Auto transplants plus Therapy

ACTIVE COMPARATOR

One autologous transplant along with a second autologous transplant will be preformed followed by one year of Dexamethasone and Thalidomide maintenance therapy.

Procedure: One Autologous TransplantProcedure: Second Autologous TransplantDrug: ThalidomideDrug: Dexamethasone

Auto transplants

ACTIVE COMPARATOR

One autologous transplant along with a second autologous transplant will be preformed followed by one year of observation.

Procedure: One Autologous TransplantProcedure: Second Autologous TransplantBehavioral: Observation

Auto and Allo transplants

ACTIVE COMPARATOR

One autologous transplant and one non-myeloablative allogeneic transplant will be preformed and followed by one year of observation.

Procedure: One Autologous TransplantProcedure: Non-Myeloablative Allogeneic TransplantBehavioral: Observation

Interventions

Melphalan will be administered at a dose of 200 mg/m2. Melphalan will be given in one dose infused on Day -2. Melphalan dose is based on ideal body weight (IBW) for patients who weigh 100-120% of their IBW. All patients will receive an autologous graft with a minimum cell dose of 2.0 x 106 CD34+ cells/kg patient weight. Patients will receive \~5 ug/kg/day of Granulocyte-Colony Stimulating Factor (G-CSF) subcutaneously from Day 5 post-transplant until absolute neutrophil count (ANC) \> 500/mm3 for two days.

Auto and Allo transplantsAuto transplantsAuto transplants plus Therapy

Upon recovery and at least Day 60 post-autograft, patients with an available 6/6 HLA matched sibling will receive an allograft after non-myeloablative conditioning. Day 0 patients will receive Total Body Irradiation (TBI) 2.0 Gy from a linear accelerator ≤ 20 cGy/min, followed by allogeneic peripheral blood stem cell (PBSC) infusion. Commence cyclosporine (CSA) on Day -3 at 5 mg/kg bid PO for a daily dose of 10 mg/kg/day through Day +84 based on actual body weight. Starting on Day 84, patients in partial or complete response with the absence of graph versus host disease (GVHD) will have CSA tapered so the patient will be off CSA by Day 180. Oral administration of Mycophenolate Mofetil will be at a daily dose of 30 mg/kg/day from the evening of Day 0 until Day 27 post-transplant.

Auto and Allo transplants

Upon recovery from the first autograft, but at least 60 days (preferably between 60-120 days) after the first autograft, patients without an HLA-matched sibling donor will receive a second autograft, also conditioned with melphalan 200 mg/m2.

Auto transplantsAuto transplants plus Therapy

Patients will be initiated on a starting dose of 50 mg/day. The dose will be increased weekly by 50 mg as tolerated to achieve a target dose of 200 mg/day. Patients will be treated for 12 months with thalidomide.

Also known as: Thalomidâ„¢
Auto transplants plus Therapy

Patients will receive dexamethasone at a dose of 40 mg per day during Days 1-4 of each month for 12 months. The first dose of dexamethasone to be given the same day the patient starts thalidomide.

Also known as: Decadron, DexPak
Auto transplants plus Therapy
ObservationBEHAVIORAL

One year of observation post-transplants.

Auto and Allo transplantsAuto transplants

Eligibility Criteria

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

You may qualify if:

  • Meeting the Durie and Salmon criteria for initial diagnosis of MM
  • Stage II or III MM at diagnosis or anytime thereafter
  • Symptomatic MM requiring treatment at diagnosis or anytime thereafter
  • Received at least three cycles of initial systemic therapy and are within 2-10 months of initiation of the initial therapy (this time frame excludes the time for mobilization therapy)
  • If receiving chemotherapy-based mobilization regimens, must be able to receive high-dose melphalan between 2 and 8 weeks after the initiation of mobilization therapy whether delivered at the transplant center or at a referring center
  • Adequate organ function as measured by:
  • Cardiac: Left ventricular ejection fraction at rest greater than 40%
  • Hepatic: Bilirubin less than 2 times the upper limit of normal and alanine transaminase (ALT) and aspartate transaminase (AST) less than 3 times the upper limit of normal
  • Renal: Creatinine clearance greater than 40 ml/min (measured or calculated/estimated)
  • Pulmonary: Carbon monoxide diffusion (DLCO), Volume forcibly exhaled in one second (FEV1), and Forced Vital Capacity (FVC) greater than 50% of predicted value (corrected for hemoglobin), or O2 saturation greater than 92% of room air
  • An adequate autologous graft defined as a cryopreserved PBSC graft containing at least 4.0 x 106 CD34+ cells/kg patient weight; if prior to enrollment it is known that a patient will be on the auto-allo arm (i.e., a consenting, eligible HLA-matched sibling donor is available), the required autograft must contain at least 2.0 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; for patients without an HLA-matched sibling donor, the autograft must be stored so that there are two products each containing at least 2 x 10\^6 CD34+ cells/kg patient weight

You may not qualify if:

  • Never advanced beyond Stage I MM since diagnosis
  • 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)
  • Plasma cell leukemia
  • Karnofsky performance score less than 70%, unless approved by the Medical Monitor or one of the Protocol Chairs
  • Uncontrolled hypertension
  • Uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms)
  • 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 Medical Monitor or one of the Protocol Chairs; cancer treated with curative intent more than 5 years previously will be allowed
  • Pregnant or breastfeeding
  • Seropositive for the human immunodeficiency virus (HIV)
  • Unwilling to use contraceptive techniques during and for 12 months following treatment
  • Prior allograft or prior autograft
  • Received mid-intensity melphalan (more than 50 mg IV) as part of prior therapy
  • Prior organ transplant requiring immunosuppressive therapy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (36)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

City of Hope Samaritan

Phoenix, Arizona, 85006, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-3000, United States

Location

Scripps Clinic/Green Hospital

La Jolla, California, 92037-1027, United States

Location

UCSD Medical Center

La Jolla, California, 92093, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

University of Florida College of Medicine (Shands)

Gainesville, Florida, 32610-100277, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

BMT Group of Georgia/Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Loyola University

Maywood, Illinois, 60156, United States

Location

IBMT (Indiana Blood and Marrow Transplant) at St Francis Franciscan Health

Indianapolis, Indiana, 46237, United States

Location

Wichita CCOP

Wichita, Kansas, 67214, United States

Location

Tufts - New England Medical Center

Boston, Massachusetts, 02111, United States

Location

DFCI/Brigham & Women's

Boston, Massachusetts, 02114, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109-0942, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Jewish Hospital BMT Program

Cincinnati, Ohio, 45236, United States

Location

University Hospitals of Cleveland/Case Western

Cleveland, Ohio, 44106, United States

Location

University of Oklahoma Medical Center

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Health Sciences University (A)

Portland, Oregon, 97239-3098, United States

Location

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Fox Chase - Temple University - BMT Program

Philadelphia, Pennsylvania, 19111-2442, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Baylor College of Medicine/The Methodist Hospital

Houston, Texas, 77030, United States

Location

University of Texas/MD Anderson Cancer Research Center

Houston, Texas, 77030, United States

Location

Texas Transplant Institute

San Antonio, Texas, 78229, United States

Location

Utah BMT/Univ of Utah Med School

Salt Lake City, Utah, 84132, United States

Location

Virginia Commonwealth University MCV Hospitals

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

University of Wisconsin Hospitals & Clinics

Madison, Wisconsin, 53792-6164, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (3)

  • Krishnan A, Pasquini MC, Logan B, Stadtmauer EA, Vesole DH, Alyea E 3rd, Antin JH, Comenzo R, Goodman S, Hari P, Laport G, Qazilbash MH, Rowley S, Sahebi F, Somlo G, Vogl DT, Weisdorf D, Ewell M, Wu J, Geller NL, Horowitz MM, Giralt S, Maloney DG; Blood Marrow Transplant Clinical Trials Network (BMT CTN). Autologous haemopoietic stem-cell transplantation followed by allogeneic or autologous haemopoietic stem-cell transplantation in patients with multiple myeloma (BMT CTN 0102): a phase 3 biological assignment trial. Lancet Oncol. 2011 Dec;12(13):1195-203. doi: 10.1016/S1470-2045(11)70243-1. Epub 2011 Sep 29.

  • Logan B, Leifer E, Bredeson C, Horowitz M, Ewell M, Carter S, Geller N. Use of biological assignment in hematopoietic stem cell transplantation clinical trials. Clin Trials. 2008;5(6):607-16. doi: 10.1177/1740774508098326.

  • Giralt S, Costa LJ, Maloney D, Krishnan A, Fei M, Antin JH, Brunstein C, Geller N, Goodman S, Hari P, Logan B, Lowsky R, Qazilbash MH, Sahebi F, Somlo G, Rowley S, Vogl DT, Vesole DH, Pasquini M, Stadtmauer E. Tandem Autologous-Autologous versus Autologous-Allogeneic Hematopoietic Stem Cell Transplant for Patients with Multiple Myeloma: Long-Term Follow-Up Results from the Blood and Marrow Transplant Clinical Trials Network 0102 Trial. Biol Blood Marrow Transplant. 2020 Apr;26(4):798-804. doi: 10.1016/j.bbmt.2019.11.018. Epub 2019 Nov 19.

MeSH Terms

Conditions

Multiple MyelomaNeoplasms, Plasma Cell

Interventions

ThalidomideDexamethasoneCalcium DobesilateObservation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

PhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedBenzenesulfonatesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsArylsulfonatesArylsulfonic AcidsSulfonic AcidsSulfur AcidsSulfur CompoundsMethodsInvestigative Techniques

Results Point of Contact

Title
Adam Mendizabal
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
CROSSOVER
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 9, 2004

First Posted

January 13, 2004

Study Start

December 1, 2003

Primary Completion

June 1, 2012

Study Completion

March 1, 2013

Last Updated

November 1, 2021

Results First Posted

August 4, 2016

Record last verified: 2017-08

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

Available IPD Datasets

Individual Participant Data Set (BMT CTN-0102)Access
Study Protocol (BMT CTN-0102)Access
Study Forms (BMT CTN-0102)Access

Locations