Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
368 participants
INTERVENTIONAL
2012-06-30
2020-09-11
Brief Summary
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Detailed Description
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Single or dual center studies have shown that partially HLA-mismatched related bone marrow (haplo-BM) and unrelated double umbilical cord blood (dUCB) are valuable sources of donor cells for RIC HCT, thus extending this treatment modality to patients who lack other donors. In order to study the reproducibility, and thus, the wider applicability of these two alternative donor strategies, The Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) conducted two parallel multicenter prospective Phase II clinical trials. These two studies evaluated the safety and efficacy of related haplo-BM (BMT CTN 0603) and dUCB (BMT CTN 0604) transplantation after RIC. Both of these alternative donor approaches produced early results similar to that reported with unrelated donor, and even HLA-matched sibling, HCT. These data demonstrate not only the efficacy of both of these approaches, but also that both can be safely exported from the single center setting. Both haplo-BM and dUCB grafts can be obtained rapidly for greater than 90% of patients lacking an HLA-matched donor. This study will test the hypothesis that progression free survival at two years after RIC haplo-BM transplantation is similar to the progression free survival after RIC dUCB transplantation.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Haploidentical Bone Marrow Transplant
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant
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
Double Umbilical Cord Blood Transplant
Participants will receive a double umbilical cord blood transplant using a reduced intensity conditioning regimen.
Double Umbilical Cord Blood Transplant
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
Interventions
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Haploidentical Bone Marrow Transplant
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
Double Umbilical Cord Blood Transplant
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
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Inclusion Criteria
* 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;
1. Patients must have available two UCB units fulfilling the following criteria:
1. 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.
2. 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).
3. Additional graft selection criteria specified in section 2.5
2. 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
Exclusion Criteria
* 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.
18 Years
70 Years
ALL
No
Sponsors
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National Heart, Lung, and Blood Institute (NHLBI)
NIH
National Cancer Institute (NCI)
NIH
Blood and Marrow Transplant Clinical Trials Network
NETWORK
National Marrow Donor Program
OTHER
Medical College of Wisconsin
OTHER
Responsible Party
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Principal Investigators
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Mary Horowitz, MD, MS
Role: STUDY_DIRECTOR
Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin
Locations
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University of Alabama at Birmingham
Birmingham, Alabama, United States
Arizona Cancer Center
Phoenix, Arizona, United States
City of Hope National Medical Center
Duarte, California, United States
University of California at Los Angeles
Los Angeles, California, United States
Stanford Hospital and Clinics
Stanford, California, United States
University of Florida College of Medicine (Shands)
Gainesville, Florida, United States
Florida Hospital Cancer Institute
Orlando, Florida, United States
Emory University
Atlanta, Georgia, United States
BMT Program at Northside Hospital
Atlanta, Georgia, United States
University of Kansas Hospital
Kansas City, Kansas, United States
Johns Hopkins University
Baltimore, Maryland, United States
DFCI Massachustts General Hospital
Boston, Massachusetts, United States
DFCI Brigham & Women's Hospital
Boston, Massachusetts, United States
University of Michigan Medical Center
Ann Arbor, Michigan, United States
Karmanos Cancer Institute/BMT
Detroit, Michigan, United States
Univeristy of Minnesota
Minneapolis, Minnesota, United States
Mayo Clinic Rochester
Rochester, Minnesota, United States
Roswell Park Cancer Center
Buffalo, New York, United States
Mt. Sinai Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University of Rochester Medical Center
Rochester, New York, United States
Stony Brook University Medical Center
Stony Brook, New York, United States
University of North Carolina Hospital at Chapel Hill
Chapel Hill, North Carolina, United States
Duke University Medical Center
Durham, North Carolina, United States
Jewish Hospital BMT Program
Cincinnati, Ohio, United States
University Hospitals of Cleveland, Case Western
Cleveland, Ohio, United States
Cleveland Clinic Foundation
Cleveland, Ohio, United States
Ohio State / Arthur G. James Cancer Hospital
Columbus, Ohio, United States
University of Oklahoma Medical Center
Oklahoma City, Oklahoma, United States
Penn State College of Medicine - The Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States
University of Pennsylvania Cancer Center
Philadelphia, Pennsylvania, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Univesity of Texas, MD Anderson CRC
Houston, Texas, United States
Texas Transplant Institute
San Antonio, Texas, United States
Virginia Commonwealth University
Richmond, Virginia, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
West Virginia University
Morgantown, West Virginia, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Countries
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References
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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.
Roth 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.
Ramsey 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.
El 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.
Brunstein 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.
Fuchs 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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Document Type: Informed Consent Form
Other Identifiers
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