Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2U10HL069294-11 | U.S. NIH Grant/Contract | View source | |
| 5U24CA076518 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| National Cancer Institute (NCI) | NIH |
| Blood and Marrow Transplant Clinical Trials Network | NETWORK |
Not provided
Not provided
Not provided
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.
Reduced intensity conditioning (RIC) blood or marrow transplantation (BMT) has allowed older and less clinically fit patients to receive potentially curative treatment with allogeneic HCT for high risk or advanced hematological malignancies. Patients lacking an HLA-matched sibling may receive a graft from a suitably HLA-matched unrelated donor. However, up to a third of patients will not have an HLA-matched sibling or a suitably matched adult unrelated donor (i.e., no more than a mismatch at a single locus). Even when a suitably matched unrelated donor is identified, data from the National Marrow Donor Program (NMDP) indicate that a median of four months is required to complete searches that result in transplantation; thus, some number of patients succumb to their disease while awaiting identification and evaluation of a suitably matched adult unrelated donor.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Haploidentical Bone Marrow Transplant | Experimental | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. |
|
| Double Umbilical Cord Blood Transplant | Experimental | Participants will receive a double umbilical cord blood transplant using a reduced intensity conditioning regimen. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Haploidentical Bone Marrow Transplant | Biological | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With PFS by Treatment Arms in Subgroups | Participants' primary diagnosis was categorized into two large groups: leukemia versus lymphoma. Age was dichotomized into two large groups: age <= 59 versus age > 59. The Kaplan-Meier estimate for PFS at 2 years post-randomization are provided for each subgroup. | Year 2 |
Not provided
Inclusion Criteria:
Additional Patient Inclusion Criteria for Conditioning:
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;
Additional Patient Inclusion Criteria for Patients Assigned to Haploidentical BM Arm: Patients must be HLA typed at high resolution using DNA based typing at the following HLA-loci: HLA-A, -B, -C and DRB1 and have available a related haploidentical BM donor with 2, 3, or 4 HLA-mismatches. A unidirectional mismatch in either the graft versus host or host versus graft direction is considered a mismatch. The donor and recipient must be HLA identical for at least one antigen (using high resolution DNA based typing) at the following genetic loci: HLA-A, HLA-B, HLA-C, and HLA-DRB1. Fulfillment of this criterion shall be considered sufficient evidence that the donor and recipient share one HLA haplotype, and typing of additional family members is not required.
Additional Patient Inclusion Criteria for Patients Assigned to Double Umbilical Cord Blood Arm:
Patients must have available two UCB units fulfilling the following criteria:
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:
Additional exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Mary Horowitz, MD, MS | Center for International Blood and Marrow Transplant Research (CIBMTR), Medical College of Wisconsin | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35233 | United States | ||
| Arizona Cancer Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24862638 | Background | 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. | |
| 24645687 | Background | 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. |
Not provided
Not provided
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).
Within 6 months of official study closure at participating sites.
Available to the public
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | dUCB | Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen. Double unrelated cord blood Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 18, 2017 | Jun 16, 2021 |
Not provided
| National Marrow Donor Program |
| OTHER |
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Double Umbilical Cord Blood Transplant | Biological | 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 |
|
| Percentage of Participants With Neutrophil Recovery |
Neutrophil recovery is defined as achieving an absolute neutrophil count greater than or equal to 500/mm^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. |
| Day 56 |
| Percentage of Participants With Platelet Recovery | Platelet recovery is defined by two different metrics as the first day of a sustained platelet count greater than 20,000/mm^3 or greater than 50,000/mm^3 with no platelet transfusions in the preceding seven days. The first day of the sustained platelet count will be designated the day of platelet engraftment. | Day 100 |
| Participants With Primary Graft Failure | Primary graft failure is defined as less than 5% donor chimerism on all measurements up to and including Day 56. | Day 56 |
| Percentage of Participants With Secondary Graft Failure | Secondary graft failure is defined as initial donor chimerism ≥ 5% declining to < 5% on subsequent measurements with time to secondary graft failure beginning at the first day of primary engraftment. | Year 2 |
| Percentage of Participants With Acute Graft-versus-Host Disease (aGVHD) | The cumulative incidences of grade II - IV and III - IV acute aGVHD will be determined. | Day 180 |
| Percentage of Participants With Chronic Graft-versus-Host Disease (cGHVD) | The cumulative incidence of cGVHD from the time of transplant will be determined. Data were collected directly from providers and chart review according to the recommendations of the NIH Consensus Conference. | Year 2 |
| Percentage of Participants With Overall Survival | Overall survival is defined as the time interval between date of randomization and death from any cause or for surviving patients, to last follow-up. The time interval between date of transplant and death from any cause or for surviving patients, to last follow-up are also analyzed. | Year 2 |
| Percentage of Participants With Treatment-related Mortality (TRM) | The cumulative incidence of TRM will be estimated, event for this endpoint is death without evidence of disease progression or recurrence. | Day 100, Day 180, Year 1, and Year 2 |
| Percentage of Participants With Relapse/Progression | Incidence of relapse/progression will be estimated using cumulative incidence function, treating death in remission as a competing risk. Relapse is defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of progressive lymphoma. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy. 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 1, year 2 |
| Toxicities | They are all Grade ≥ 3 toxicities based on NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4. | Day 28, Day 56, Day 180, 1 year, and 2 years |
| Participants With Infections | All Grade 2 and 3 infections will be reported. Grade 1 CMV infections through Day 56 will also be reported. | Up to 2 years |
| Hospital Admission and Length of Stay | Total Time Alive and Not Hospitalized within 6 Months Post Randomization | Month 6 |
| 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 |
| 41350757 | Derived | Zhang 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. |
| 39846144 | Derived | Khanal M, Logan BR, Banerjee A, Fang X, Ahn KW. A Commensurate Prior Model With Random Effects for Survival and Competing Risk Outcomes to Accommodate Historical Controls. Pharm Stat. 2025 Jan-Feb;24(1):e2464. doi: 10.1002/pst.2464. |
| 37120135 | Derived | 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. |
| 37088401 | Derived | 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. |
| 34273598 | Derived | 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. |
| 33475736 | Derived | 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. |
| FG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Baseline characteristics for all enrolled participants by treatment arm.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | dUCB | Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen. Double unrelated cord blood Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
| BG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Full Range | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Karnofsky Performance Score | KPS describes patient-perceived global quality of life and functioning on a scale of 0-100. 100: No evidence of disease; 90: Normal activity. Minor signs or symptoms of disease; 80: Normal activity with effort. Some signs or symptoms of disease; 70: Cares for self. Unable to continue normal activity; 60: Needs occasional assistance, but cares for most personal needs; 50: Needs considerable assistance and medical care; 40: Disabled. Needs special care and assistance; 30: Severely disabled. Hospital admission indicated; 20: Very sick. Active supportive therapy needed; 10: Moribund; 0: Dead | Count of Participants | Participants |
| |||||||||||||||
| Primary Diagnosis | Count of Participants | Participants |
| ||||||||||||||||
| Disease Risk for Leukemia Patients (N=272) | Remission is defined as < 5% blasts with no morphological characteristics of acute leukemia (e.g., Auer Rods) in a bone marrow with > 20% cellularity, peripheral blood counts showing ANC >1000/µl, including patients in CRp. | Disease risk is assessed in enrolled Leukemia patients. | Count of Participants | Participants |
| ||||||||||||||
| Disease Risk for Lymphoma Patients (N=96) | Complete Response is defined as disappearance of all evidence of disease. Partial Response is defined as regression of measurable disease and no new sites. | Disease risk is assessed in enrolled Lymphoma patients. | Count of Participants | Participants |
| ||||||||||||||
| Cytogenetics for Leukemia | For Adult acute myeloid leukemia (AML), Favorable: t(15:17), inv(16), del(16q), t(16:16), [t(8:21) without del(9q) or complex]; Intermediate: normal karyotype, +6, +8, -Y, del(12p), 11q23, t(9:11); Poor: complex karyotype, -5/del(5q), -7/del(7q), abn(3q, 9q, 11q, 21q, 17p), t(6:9), t(9:22). For Acute lymphocytic leukemia (ALL), Poor: Ph+/t(9:22), t(4:11), 11q23, MLL, hypodiploid, t(8:14), complex. For Chronic lymphocytic leukemia (CLL), Intermediate: other; Poor: 17p-, 11q-, complex (>= 5). | Cytogenetics data on leukemia participants were retrieved from CIBMTR. Data is only measured in enrolled Leukemia patients. | Count of Participants | Participants |
| ||||||||||||||
| HLA Matching Score for Haploidentical Donor at Randomization | HLA Match Score includes genetic matching information at HLA-A, -B, and -DRB1 loci or HLA-A, -B, -C, and -DRB1 loci. Matching at all HLA-A, -B, and -DRB1 loci is designated as 6/6 HLA matching. A 4/6 HLA match includes mismatches at any two loci. Matching at all HLA-A, -B, -C, and -DRB1 loci is designated as 8/8 HLA matching. A 6/8 HLA match includes mismatches at any two loci. Note: *Not required if potential haplo-donor is a biological parent or child | Count of Participants | Participants |
| |||||||||||||||
| HLA Matching Score for Cord Blood Unit 1 at Enrollment | Matching at all HLA-A, -B, and -DRB1 loci is designated as 6/6 HLA matching. A 4/6 HLA match includes mismatches at any two loci. | Count of Participants | Participants |
| |||||||||||||||
| HLA Matching Score for Cord Blood Unit 2 at Enrollment | Matching at all HLA-A, -B, and -DRB1 loci is designated as 6/6 HLA matching. A 4/6 HLA match includes mismatches at any two loci. | Count of Participants | Participants |
| |||||||||||||||
| Pre-cryopreservation total nucleated cell count | Statistics is summarized on available data. | Median | Full Range | cells x 10^7/kg |
| ||||||||||||||
| Post-thaw total nucleated cell count | Statistics is summarized on available data. | Median | Full Range | cells x 10^7/kg |
| ||||||||||||||
| Total nucleated cell count at infusion | Statistics is summarized on available data. | Median | Full Range | cells x 10^7/kg |
| ||||||||||||||
| Pre-cryopreservation CD34+ cell count | Statistics is summarized on available data. | Median | Full Range | cells x 10^6/kg |
| ||||||||||||||
| Post-thaw CD34+ cell count | Statistics is summarized on available data. | Median | Full Range | cells x 10^6/kg |
| ||||||||||||||
| CD34+ cell count at infusion | Statistics is summarized on available data. | Median | Full Range | cells x 10^6/kg |
| ||||||||||||||
| Pre-cryopreservation CD3+ cell count | Statistics is summarized on available data. | Median | Full Range | cells x 10^6/kg |
| ||||||||||||||
| Post-thaw CD3+ cell count | Statistics is summarized on available data. | Median | Full Range | cells x 10^6/kg |
| ||||||||||||||
| CD3+ cell count at infusion | Statistics is summarized on available data. | Median | Full Range | cells x 10^6/kg |
| ||||||||||||||
| HCT-comorbidity index (CI) | The HCT-CI was developed to identify comorbidities relevant to transplant and act as a tool for risk assessment and before allogeneic hematopoietic stem cell transplantation. Patients with no comorbidities are assigned a score of zero. Arrhythmia, cardiac, bowel, diabetes, cerebrovascular, psychological, mild chronic hepatitis, obesity, infection are assigned a score of 1. Rheumatoid arthritis, peptic ulcer, renal moderate/severe, pulmonary moderate, are assigned a score of 2. Solid tumor, heart valve disease, pulmonary sever, hepatic moderate/severe are assigned a score of 3. | HCT-CI was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted. | Count of Participants | Participants |
| ||||||||||||||
| CMV Status at Transplant | Cytomegalovirus (CMV) status | CMV status was only measured in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted. | Count of Participants | Participants |
| ||||||||||||||
| Time from Diagnosis to Transplant | Time to transplant was only calculated in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted. | Median | Full Range | day |
| ||||||||||||||
| Prior Autologous Transplant | Count of Participants | Participants |
| ||||||||||||||||
| Number of Regimens Prior to Transplant | Number of regimens prior to transplant was only counted in the transplanted participants. The total number of participants is different from the overall number of enrolled participants as 11 participants from dUCB arm and 15 participants from Haplo-BM arm were not transplanted. | Count of Participants | Participants |
| |||||||||||||||
| Disease Risk Index | The disease risk index was computed based on participant's primary diagnosis, disease risk and cytogenetic data. | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | The primary endpoint analysis is performed using the intent-to-treat principle so that all randomized patients are included in the analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Year 2 |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With PFS by Treatment Arms in Subgroups | Participants' primary diagnosis was categorized into two large groups: leukemia versus lymphoma. Age was dichotomized into two large groups: age <= 59 versus age > 59. The Kaplan-Meier estimate for PFS at 2 years post-randomization are provided for each subgroup. | The randomized participants are included in the analysis. | Posted | Number | 95% Confidence Interval | percentage of participants | Year 2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Neutrophil Recovery | Neutrophil recovery is defined as achieving an absolute neutrophil count greater than or equal to 500/mm^3 for three consecutive measurements on three different days. The first of the three days will be designated the day of neutrophil recovery. | The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 56 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Platelet Recovery | Platelet recovery is defined by two different metrics as the first day of a sustained platelet count greater than 20,000/mm^3 or greater than 50,000/mm^3 with no platelet transfusions in the preceding seven days. The first day of the sustained platelet count will be designated the day of platelet engraftment. | The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 100 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Participants With Primary Graft Failure | Primary graft failure is defined as less than 5% donor chimerism on all measurements up to and including Day 56. | The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded. | Posted | Count of Participants | Participants | Day 56 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Secondary Graft Failure | Secondary graft failure is defined as initial donor chimerism ≥ 5% declining to < 5% on subsequent measurements with time to secondary graft failure beginning at the first day of primary engraftment. | The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded. | Posted | Number | 95% Confidence Interval | percentage of participants | Year 2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Acute Graft-versus-Host Disease (aGVHD) | The cumulative incidences of grade II - IV and III - IV acute aGVHD will be determined. | The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 180 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Chronic Graft-versus-Host Disease (cGHVD) | The cumulative incidence of cGVHD from the time of transplant will be determined. Data were collected directly from providers and chart review according to the recommendations of the NIH Consensus Conference. | The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded. | Posted | Number | 95% Confidence Interval | percentage of participants | Year 2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Overall Survival | Overall survival is defined as the time interval between date of randomization and death from any cause or for surviving patients, to last follow-up. The time interval between date of transplant and death from any cause or for surviving patients, to last follow-up are also analyzed. | The randomized or transplanted participants are included in the analyses. | Posted | Number | 95% Confidence Interval | percentage of participants | Year 2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Treatment-related Mortality (TRM) | The cumulative incidence of TRM will be estimated, event for this endpoint is death without evidence of disease progression or recurrence. | The randomized or transplanted participants are included in the analyses. | Posted | Number | 95% Confidence Interval | percentage of participants | Day 100, Day 180, Year 1, and Year 2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants With Relapse/Progression | Incidence of relapse/progression will be estimated using cumulative incidence function, treating death in remission as a competing risk. Relapse is defined by either morphological or cytogenetic evidence of acute leukemia consistent with pre-transplant features, or radiologic evidence of progressive lymphoma. When in doubt, the diagnosis of recurrent or progressive lymphoma should be documented by tissue biopsy. 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. | The randomized or transplanted participants are included in the analyses. | Posted | Number | 95% Confidence Interval | percentage of participants | Year 1, year 2 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Toxicities | They are all Grade ≥ 3 toxicities based on NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4. | The transplanted participants are included in the analysis. A total of 26 patients (11 on the dUCB arm and 15 on the Haplo-BM arm) who did not proceed to the study transplant are excluded. | Posted | Number | Toxicities | Day 28, Day 56, Day 180, 1 year, and 2 years |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Participants With Infections | All Grade 2 and 3 infections will be reported. Grade 1 CMV infections through Day 56 will also be reported. | The transplanted participants are included in the analysis. | Posted | Count of Participants | Participants | Up to 2 years |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Hospital Admission and Length of Stay | Total Time Alive and Not Hospitalized within 6 Months Post Randomization | The randomized participants are included in the analysis. | Posted | Mean | Standard Deviation | Days | Month 6 |
|
Adverse event reporting and monitoring were conducted throughout the study, up to 2 years.
Adverse event (AE) reporting was conducted according to the BMT CTN's manual of operating procedures (MOP). Unexpected, grade 3-5 AE were reported through an expedited AE reporting system. Expected AEs were reported using National Cancer Institute (NCI)'s Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 at regular intervals and reported in the secondary outcome "Toxicities". All fatal (Grade 5) expected adverse events were reported in an expedited manner.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | dUCB | Participants will receive double unrelated cord blood transplant using a reduced intensity conditioning regimen. Double unrelated cord blood Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 1 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days | 97 | 186 | 4 | 186 | 1 | 186 |
| EG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days | 74 | 182 | 9 | 182 | 0 | 182 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardio-respiratory arrest | Cardiac disorders | MedDRA version 20.0 | Non-systematic Assessment | Cardiorespiratory |
|
| Supraventricular tachycardia | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.0 | Non-systematic Assessment | Supraventricular tachycardia |
|
| Arterial injury | Injury, poisoning and procedural complications | MedDRA version 20.0 | Non-systematic Assessment | Arterial injury |
|
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA version 20.0 | Non-systematic Assessment | Infusion related reaction |
|
| Vascular access complication | Injury, poisoning and procedural complications | MedDRA version 20.0 | Non-systematic Assessment | Vascular access complication |
|
| Acute myeloid leukemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 20.0 | Non-systematic Assessment | Acute myeloid leukemia |
|
| Central nervous system lesion | Nervous system disorders | MedDRA version 20.0 | Non-systematic Assessment | Central nervous system lesion |
|
| Syncope | Nervous system disorders | MedDRA version 20.0 | Non-systematic Assessment | Syncope |
|
| Psychiatric disorders Delirium | Psychiatric disorders | MedDRA version 20.0 | Non-systematic Assessment | Psychiatric disorders Delirium |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 20.0 | Non-systematic Assessment | Respiratory failure |
|
| Embolism | Vascular disorders | MedDRA version 20.0 | Non-systematic Assessment | Embolism |
|
| Hypotension | Vascular disorders | MedDRA version 20.0 | Non-systematic Assessment | Hypotension |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Myelodysplastic syndrome | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA version 20.0 | Non-systematic Assessment | MYELODYSPLASTIC SYNDROME |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Adam Mendizabal, PhD | The Emmes Company | (301) 251-1161 | 10221 | amendizabal@emmes.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 24, 2018 | Jun 16, 2021 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jan 18, 2017 | Jun 16, 2021 | ICF_002.pdf |
| ID | Term |
|---|---|
| D054198 | Precursor Cell Lymphoblastic Leukemia-Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| D002051 | Burkitt Lymphoma |
| D008224 | Lymphoma, Follicular |
| D006689 | Hodgkin Disease |
| D020522 | Lymphoma, Mantle-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D007938 | Leukemia |
| ID | Term |
|---|---|
| D007945 | Leukemia, Lymphoid |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D007951 | Leukemia, Myeloid |
| D020031 | Epstein-Barr Virus Infections |
| D006566 | Herpesviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
| D014412 | Tumor Virus Infections |
| D016393 | Lymphoma, B-Cell |
Not provided
Not provided
|
|
|
|
|
| Acute Myelogeneous Leukemia |
|
|
| Biphenotypic/Undifferentiated/Prolymphocytic Leukemia |
|
|
| Hodgkin's Lymphoma |
|
|
| Large Cell Lymphoma |
|
|
| Follicular Non-Hodgkin's Lymphoma |
|
|
| T-cell Leukemia/Lymphoma |
|
|
| Mantle Cell Lymphoma |
|
|
| Other Lymphoma |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
The null hypothesis of the study is that there is no difference between the 2 year PFS probabilities for dUCB vs. haplo-BM after adjustment for age, performance score, and disease type. |
| Regression, Cox |
| 0.060 |
Statistical significance was determined using a pre-specified threshold of 0.05 |
| Hazard Ratio (HR) |
| 1.30 |
| 2-Sided |
| 95 |
| 0.99 |
| 1.70 |
| Superiority |
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
|
| OG001 | Haplo-BM | Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen. Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes: - Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days |
|
|
Participants will receive haploidentical bone marrow transplant using a reduced intensity conditioning regimen.
Haploidentical Bone Marrow Transplant: The conditioning regimen consists of:
The GVHD prophylaxis regimen consists of:
Supportive care includes:
- Filgrastim (G-CSF) 5 mcg/kg/day beginning Day 5 until ANC >1500/mm3 for 3 consecutive measurements on at least two different days
|
|
|