Double Cord Versus Haploidentical (BMT CTN 1101)
A Multi-Center, Phase III, Randomized Trial of RIC and Transplantation of (dUCB) Versus HLA-Haplo Related Bone Marrow for Patients With Hematologic Malignancies.(BMT CTN #1101)
3 other identifiers
interventional
368
1 country
39
Brief Summary
Hematopoietic cell transplants (HCT)are one treatment option for people with leukemia or lymphoma. Family members,unrelated donors or banked umbilical cordblood units with similar tissue type can be used for HCT. This study will compare the effectiveness of two new types of bone marrow transplants in people with leukemia or lymphoma: one that uses bone marrow donated from family members with only partially matched bone marrow; and, one that uses two partially matched cord blood units.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Jun 2012
Longer than P75 for phase_3
39 active sites
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
May 10, 2012
CompletedFirst Posted
Study publicly available on registry
May 14, 2012
CompletedStudy Start
First participant enrolled
June 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 11, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
September 11, 2020
CompletedResults Posted
Study results publicly available
December 1, 2021
CompletedDecember 1, 2021
November 1, 2021
8.3 years
May 10, 2012
September 10, 2021
November 2, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Progression Free Survival (PFS)
The primary endpoint is PFS at 2 years post-randomization. Death or disease relapse/progression will be considered as events. The time to event is defined as the time interval from randomization to relapse/progression, to death or to last follow-up, whichever comes first. Relapse is defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of progressive lymphoma. Minimal residual disease will not be considered evidence of relapse, however, minimal residual disease that progresses will be considered as relapse and the date of relapse will be the date of detection of minimal residual disease that prompted an intervention by the treating physician. Finally, institution of any therapy to treat persistent, progressive or relapsed disease, including withdrawal of immunosuppressive therapy or DLI, will be considered evidence of relapse/progression regardless of whether the criteria described above are met.
Year 2
Secondary Outcomes (13)
Percentage of Participants With PFS by Treatment Arms in Subgroups
Year 2
Percentage of Participants With Neutrophil Recovery
Day 56
Percentage of Participants With Platelet Recovery
Day 100
Participants With Primary Graft Failure
Day 56
Percentage of Participants With Secondary Graft Failure
Year 2
- +8 more secondary outcomes
Study Arms (2)
Haploidentical Bone Marrow Transplant
EXPERIMENTALParticipants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Double Umbilical Cord Blood Transplant
EXPERIMENTALParticipants will receive a double umbilical cord blood transplant using a reduced intensity conditioning regimen.
Interventions
The conditioning regimen consists of: Fludarabine (Flu)30 mg/m2 IV Days -6, -5, -4, -3, -2 Cyclophosphamide (Cy) 14.5 mg/kg IV Days -6, -5 Total body irradiation (TBI) 200cGy Day -1 The GVHD prophylaxis regimen consists of: Cy 50 mg/kg IV Days 3, 4 Tacrolimus (IV or PO) beginning Day 5 Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day 5 until Day 35
The preparative regimen consists of: Fludarabine 40 mg/m2 IV Days -6, -5, -4,-3, -2 Cyclophosphamide 50 mg/kg IV Day -6 Total Body Irradiation (TBI) 200 cGy Day -1 for patients who have received cytotoxic chemotherapy within the 3 months of enrollment or an autologous transplant within 24 months of enrollment or 300 cGy Day -1 for patients who have not received cytotoxic chemotherapy within the 3 months of enrollment and who have not received an autologous transplant within 24 months of enrollment. The GVHD prophylaxis regimen consists of: Cyclosporine beginning Day -3 with dose adjusted to maintain a trough level of 200-400 ng/mL. Mycophenolate mofetil (MMF) 15 mg/kg po three times a day, maximum dose 1 g po TID beginning Day -3 until Day 35
Eligibility Criteria
You may qualify if:
- Patients 18 to 70 years old
- Patients must have available both: a)One or more potential related mismatched donors (biologic parent(s) or siblings (full or half) or children). At least low resolution DNA based human leukocyte antigen (HLA) typing at HLA-A, -B, and -DRB1 for potential haploidentical sibling donors is required. b)At least two potential umbilical cord blood units identified. Each unit must have a minimum of 1.5 x 10\^7/kg pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units, the minimum pre-cryopreserved total nucleated cell dose of each unit must be at least 2.0 x 10\^7/kg. Units must be HLA matched at a minimum of 4/6 to the recipient at HLA-A, HLA-B (at low resolution using DNA based typing) and HLA-DRB1 (at high resolution using DNA based typing). Confirmatory typing is not required for randomization.
- Acute Lymphoblastic Leukemia (ALL) in first complete remission (CR1) that is NOT considered favorable-risk as defined by the presence of at least one of the following: Adverse cytogenetics such as t(9;22), t(1;19), t(4;11), other Mixed Lineage Leukemia (MLL) rearrangements; White blood cell counts of greater than 30,000/mcL (B-ALL) or greater than 100,000/mcL (T-ALL)at diagnosis; Recipient age older than 30 years at diagnosis; Time to CR greater than 4 weeks
- Acute Myelogeneous Leukemia (AML) in CR1 that is NOT considered as favorable-risk. Favorable risk is defined as having one of the following: t(8.21) without CKIT mutation, inv(16) without CKIT mutation or t(16;16), normal karyotype with mutated NPM1 and not FLT-ITD, normal karyotype with double mutated CEBPA, Acute promyelocytic leukemia (APL) in first molecular remission at end of consolidation
- Acute Leukemias in 2nd or subsequent CR
- Biphenotypic/Undifferentiated/Prolymphocytic Leukemias in first or subsequent CR, adult T-cell leukemia/lymphoma in first or subsequent CR
- Burkitt's lymphoma: second or subsequent CR
- Lymphoma fulfilling the following criteria: Chemotherapy-sensitive (at least stable disease lymphomas that have failed at least 1 prior regimen of multi-agent chemotherapy and are INELIGIBLE for an autologous transplant. Patients with chronic lymphocytic leukemia (CLL) are not eligible regardless of disease status.
- Performance status: Karnofsky score greater than or equal to 70%.
- Patients with Adequate Physical Function as Measured by: a. Cardiac: Left ventricular ejection fraction at rest must be greater than or equal to 40%, or shortening fraction less than 25%; b. Hepatic: Bilirubin less than or equal to 2.5 mg/dL, except for patients with Gilbert's syndrome or hemolysis. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Alkaline Phosphatase less than 5 x upper limit of normal; c. Renal: Serum creatinine within normal range, or if serum creatinine outside normal range, then renal function (measured or estimated creatinine clearance or GFR)greater than 40 mL/min/1.73m\^; d. Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) greater than 50% predicted;
- Patients must have available two UCB units fulfilling the following criteria:
- Each unit must have a minimum of 1.5 x 10\^7/kg pre-cryopreserved total nucleated cell dose. For non-red blood cell depleted units, the minimum pre-cryopreserved total nucleated cell dose of each unit must be at least 2.0 x10\^7/kg.
- Units must be HLA matched at a minimum of 4/6 to the recipient at HLA -A, HLA-B (at low resolution using DNA based typing), and HLA -DRB1 (at high resolution using DNA based typing).
- Additional graft selection criteria specified in section 2.5
- Patients must have received at least one cycle of the cytotoxic chemotherapy regimens (or regimen of similar intensity) listed in Appendix D within 3 months of enrollment (measured from the start date of chemotherapy) OR have had an autologous transplant within 24 months of enrollment OR receive 300 cGy as part of the preparative regimen
You may not qualify if:
- Patients with suitably matched related or unrelated donor, as defined per institutional practice.
- Recipients of prior autologous hematopoietic stem cell transplantation are ineligible if disease recurrence occurred less than 6 months from their autologous stem cell transplant.
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- Prior allogeneic HCT.
- Patients with history of primary idiopathic myelofibrosis or any severe marrow fibrosis.
- Planned use of prophylactic donor lymphocyte infusion (DLI) therapy.
- Anti-donor HLA antibodies.
- Pregnancy or breast-feeding.
- Evidence of HIV infection or known HIV positive serology.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Medical College of Wisconsinlead
- National Heart, Lung, and Blood Institute (NHLBI)collaborator
- National Cancer Institute (NCI)collaborator
- Blood and Marrow Transplant Clinical Trials Networkcollaborator
- National Marrow Donor Programcollaborator
Study Sites (39)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
Arizona Cancer Center
Phoenix, Arizona, 85013, United States
City of Hope National Medical Center
Duarte, California, 91010-3000, United States
University of California at Los Angeles
Los Angeles, California, 90095, United States
Stanford Hospital and Clinics
Stanford, California, 94305, United States
University of Florida College of Medicine (Shands)
Gainesville, Florida, 32610-0277, United States
Florida Hospital Cancer Institute
Orlando, Florida, 32804, United States
Emory University
Atlanta, Georgia, 30322, United States
BMT Program at Northside Hospital
Atlanta, Georgia, 30342, United States
University of Kansas Hospital
Kansas City, Kansas, 66160, United States
Johns Hopkins University
Baltimore, Maryland, 21231, United States
DFCI Massachustts General Hospital
Boston, Massachusetts, 02114, United States
DFCI Brigham & Women's Hospital
Boston, Massachusetts, 02115, United States
University of Michigan Medical Center
Ann Arbor, Michigan, 48109, United States
Karmanos Cancer Institute/BMT
Detroit, Michigan, 48201, United States
Univeristy of Minnesota
Minneapolis, Minnesota, 55455, United States
Mayo Clinic Rochester
Rochester, Minnesota, 55905, United States
Roswell Park Cancer Center
Buffalo, New York, 14203, United States
Mt. Sinai Medical Center
New York, New York, 10029, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Rochester Medical Center
Rochester, New York, 14642, United States
Stony Brook University Medical Center
Stony Brook, New York, 11794-7122, United States
University of North Carolina Hospital at Chapel Hill
Chapel Hill, North Carolina, 27599-7305, United States
Duke University Medical Center
Durham, North Carolina, 27705, United States
Jewish Hospital BMT Program
Cincinnati, Ohio, 45236, United States
University Hospitals of Cleveland, Case Western
Cleveland, Ohio, 44106-5061, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State / Arthur G. James Cancer Hospital
Columbus, Ohio, 43210, United States
University of Oklahoma Medical Center
Oklahoma City, Oklahoma, 73104, United States
Penn State College of Medicine - The Milton S. Hershey Medical Center
Hershey, Pennsylvania, 17033, United States
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, 19104, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
Univesity of Texas, MD Anderson CRC
Houston, Texas, 77030, United States
Texas Transplant Institute
San Antonio, Texas, 78229, United States
Virginia Commonwealth University
Richmond, Virginia, 23298, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109-1024, United States
West Virginia University
Morgantown, West Virginia, 26506-9162, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53211, United States
Related Publications (7)
Eapen M, O'Donnell P, Brunstein CG, Wu J, Barowski K, Mendizabal A, Fuchs EJ. Mismatched related and unrelated donors for allogeneic hematopoietic cell transplantation for adults with hematologic malignancies. Biol Blood Marrow Transplant. 2014 Oct;20(10):1485-92. doi: 10.1016/j.bbmt.2014.05.015. Epub 2014 May 23.
PMID: 24862638BACKGROUNDRoth JA, Bensink ME, O'Donnell PV, Fuchs EJ, Eapen M, Ramsey SD. Design of a cost-effectiveness analysis alongside a randomized trial of transplantation using umbilical cord blood versus HLA-haploidentical related bone marrow in advanced hematologic cancer. J Comp Eff Res. 2014 Mar;3(2):135-44. doi: 10.2217/cer.13.95.
PMID: 24645687BACKGROUNDZhang P, Logan B, Martens MJ. Covariate-Adjusted Group Sequential Comparisons of Survival Probabilities. Stat Med. 2025 Dec;44(28-30):e70339. doi: 10.1002/sim.70339.
PMID: 41350757DERIVEDRamsey SD, Bansal A, Li L, O'Donnell PV, Fuchs EJ, Brunstein CG, Eapen M, Thao V, Roth JA, Steuten LMG. Cost-Effectiveness of Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Bone Marrow Transplantation: Evidence from BMT CTN 1101. Transplant Cell Ther. 2023 Jul;29(7):464.e1-464.e8. doi: 10.1016/j.jtct.2023.04.017. Epub 2023 Apr 27.
PMID: 37120135DERIVEDEl Jurdi N, Martens MJ, Brunstein CG, O'Donnell P, Lee SJ, D'Souza A, Logan B, Hong S, Singh AK, Sandhu K, Shapiro RM, Horowitz MM, Hamilton BK. Health-Related Quality of Life in Double Umbilical Cord Blood versus Haploidentical Marrow Transplantation: A Quality of Life Analysis Report of BMT CTN 1101. Transplant Cell Ther. 2023 Jul;29(7):467.e1-467.e5. doi: 10.1016/j.jtct.2023.04.009. Epub 2023 Apr 22.
PMID: 37088401DERIVEDBrunstein CG, DeFor TE, Fuchs EJ, Karanes C, McGuirk JP, Rezvani AR, Eapen M, O'Donnell PV, Weisdorf DJ; Blood and Marrow Transplant Clinical Trials Network. Engraftment of Double Cord Blood Transplantation after Nonmyeloablative Conditioning with Escalated Total Body Irradiation Dosing to Facilitate Engraftment in Immunocompetent Patients. Transplant Cell Ther. 2021 Oct;27(10):879.e1-879.e3. doi: 10.1016/j.jtct.2021.07.006. Epub 2021 Jul 15.
PMID: 34273598DERIVEDFuchs EJ, O'Donnell PV, Eapen M, Logan B, Antin JH, Dawson P, Devine S, Horowitz MM, Horwitz ME, Karanes C, Leifer E, Magenau JM, McGuirk JP, Morris LE, Rezvani AR, Jones RJ, Brunstein CG. Double unrelated umbilical cord blood vs HLA-haploidentical bone marrow transplantation: the BMT CTN 1101 trial. Blood. 2021 Jan 21;137(3):420-428. doi: 10.1182/blood.2020007535.
PMID: 33475736DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Adam Mendizabal, PhD
- Organization
- The Emmes Company
Study Officials
- STUDY DIRECTOR
Mary Horowitz, MD, MS
Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
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
Study Record Dates
First Submitted
May 10, 2012
First Posted
May 14, 2012
Study Start
June 1, 2012
Primary Completion
September 11, 2020
Study Completion
September 11, 2020
Last Updated
December 1, 2021
Results First Posted
December 1, 2021
Record last verified: 2021-11
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, ICF
- Time Frame
- Within 6 months of official study closure at participating sites.
- Access Criteria
- Available to the public
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).