Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)
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ClinicalTrials.gov Identifier: NCT01339910 |
Recruitment Status :
Terminated
(Accrual terminated as recommended by the data and safety monitoring board.)
First Posted : April 21, 2011
Results First Posted : May 30, 2018
Last Update Posted : January 4, 2023
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Study Type | Interventional |
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Study Design | Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment |
Condition |
Leukemia, Myelocytic, Acute |
Interventions |
Drug: Fludarabine and Busulfan Drug: Fludarabine and Melphalan Drug: Busulfan and Fludarabine Drug: Busulfan and Cyclophosphamide Drug: Cyclophosphamide and Total Body Irradiation |
Enrollment | 272 |
Recruitment Details | Participants were enrolled between June 2011 and April 2014 from 32 transplant centers |
Pre-assignment Details |
Arm/Group Title | Myeloablative Conditioning Regimen (MAC) | Reduced Intensity Conditioning (RIC) |
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Arm/Group Description |
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu)
Busulfan and Cyclophosphamide: (Bu/Cy)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
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One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu)
Fludarabine and Melphalan: (Flu/Mel)
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Period Title: Overall Study | ||
Started | 135 | 137 |
Completed | 132 | 133 |
Not Completed | 3 | 4 |
Reason Not Completed | ||
Withdrawal by Subject | 1 | 0 |
Physician Decision | 1 | 0 |
Disease relapse | 1 | 4 |
Arm/Group Title | Myeloablative Conditioning Regimen (MAC) | Reduced Intensity Conditioning (RIC) | Total | |
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Arm/Group Description |
One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation. Busulfan and Fludarabine: (Bu/Flu)
Busulfan and Cyclophosphamide: (Bu/Cy)
Cyclophosphamide and Total Body Irradiation: (Cy/TBI)
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One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu)
Fludarabine and Melphalan: (Flu/Mel)
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Total of all reporting groups | |
Overall Number of Baseline Participants | 135 | 137 | 272 | |
Baseline Analysis Population Description |
[Not Specified]
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Age, Continuous
Median (Full Range) Unit of measure: Years |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
54.8
(21.9 to 66.0)
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54.8
(21.9 to 65.9)
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54.8
(21.9 to 66.0)
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Sex: Female, Male
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Female |
59 43.7%
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70 51.1%
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129 47.4%
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Male |
76 56.3%
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67 48.9%
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143 52.6%
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Primary Disease
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Acute Myeloid Leukemia (AML) |
108 80.0%
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110 80.3%
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218 80.1%
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Myelodysplastic Syndrome (MDS) |
27 20.0%
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27 19.7%
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54 19.9%
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MDS WHO Classification
[1] [2] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 27 participants | 27 participants | 54 participants | |
RA/RARS/RCMD/RCMD-RS/Del-5q/MDS-U |
16 59.3%
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17 63.0%
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33 61.1%
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RAEB-1 |
5 18.5%
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5 18.5%
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10 18.5%
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RAEB-2 |
6 22.2%
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5 18.5%
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11 20.4%
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[1]
Measure Description:
Participants with MDS are categorized per 2008 WHO classification (Vardiman et al. 2009). Major features of each class are given below: Refractory Anemia (RA): Anemia without marrow blasts or sideroblasts; Refractory Anemia with Ringed Sideroblasts (RARS): > 15% marrow sideroblasts; Refractory Cytopenias with Multilineage Dysplasia (RCMD): Dysplasia in >10% marrow cells; Isolated del(5q) (Del-5q): Isolated del(5q) in marrow; Unclassified (MDS-U) Refractory Anemia with Excess Blasts-1 (RAEB-1): 5-9% marrow blasts; Refractory Anemia with Excess Blasts-2 (RAEB-2): 10-19% marrow blasts; [2]
Measure Analysis Population Description: Participants with MDS
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AML WHO Classification
[1] [2] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 108 participants | 110 participants | 218 participants | |
AML with recurrent genetic abnormalities |
12 11.1%
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20 18.2%
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32 14.7%
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AML with multilineage dysplasia |
8 7.4%
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12 10.9%
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20 9.2%
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AML and MDS, therapy related |
2 1.9%
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3 2.7%
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5 2.3%
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AML, not otherwise specified |
86 79.6%
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75 68.2%
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161 73.9%
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[1]
Measure Description:
Participants with AML are categorized per 2008 WHO classification (Vardiman et al. 2009). Major features of each class are given below: AML with recurrent genetic abnormalities: Presence of specific genetic abnormalities known to be prognostic; AML with multilineage dysplasia: > 50% of cells in at least 2 myeloid lineages are dysplastic; AML and MDS, therapy related: development of myeloid neoplasms in response to therapy that is diagnosed as either AML or MDS; AML not otherwise specified: AML that does not satisfy criteria for other classes [2]
Measure Analysis Population Description: Participants with AML
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Disease Duration
Median (Full Range) Unit of measure: Months |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
6
(2 to 86)
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6
(2 to 130)
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6
(2 to 130)
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Disease Risk Status
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Standard |
74 54.8%
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71 51.8%
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145 53.3%
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High |
54 40.0%
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61 44.5%
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115 42.3%
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Unknown |
7 5.2%
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5 3.6%
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12 4.4%
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[1]
Measure Description: Disease risk status is defined according to cytogenetic and molecular abnormalities identified prior to transplantation and classified as standard or high risk. Among AML participants, high-risk disease is defined as the presence of cytogenetic abnormalities at 3q, 9q, 11q, 20q, 21q, or 17p; the presence of del(5q)/-5, -7/del(7q), t(6;9), or t(9;22); and/or FLT-3 internal tandem duplication mutation. Among MDS participants, high-risk disease is defined as the presence of > 10% blasts in bone marrow.
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HCT-CI
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
0 |
46 34.1%
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40 29.2%
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86 31.6%
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1-2 |
45 33.3%
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52 38.0%
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97 35.7%
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3 or more |
42 31.1%
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44 32.1%
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86 31.6%
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Unknown |
2 1.5%
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1 0.7%
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3 1.1%
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[1]
Measure Description: The Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) (Sorror et al., 2005) summarizes relevant comorbidities present in participants prior to allogeneic transplant. Each comorbidity reported at the time of transplant is given a score of 0, 1, 2, or 3 and the overall HCT-CI score is the sum of the comorbidity scores, ranging from 0 - 26.
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Conditioning Regimen
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Flu/Bu4 |
87 64.4%
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0 0.0%
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87 32.0%
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Bu/Cy |
40 29.6%
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0 0.0%
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40 14.7%
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Cy/TBI |
8 5.9%
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0 0.0%
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8 2.9%
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Flu/Mel |
0 0.0%
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27 19.7%
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27 9.9%
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Flu/Bu2 |
0 0.0%
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110 80.3%
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110 40.4%
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[1]
Measure Description:
Flu/Bu4: busulfan (16 mg/kg oral or 12.8 mg/kg IV) and fludarabine (120-180 mg/m2); Bu/Cy: busulfan (16 mg/kg oral or 12.8 mg/kg IV) and cyclophosphamide (120 mg/kg) ; Cy/TBI: cyclophosphamide (120 mg/kg) and total body irradiation (1200-1420 cGy); Flu/Mel: fludarabine (120-180 mg/m2) and melphalan (≤ 150 mg/m2); Flu/Bu2: fludarabine (120-180 mg/m2) with busulfan (≤ 8 mg/kg oral or 6.4 mg/kg IV); Flu/Bu4, Bu/Cy, and Cy/TBI are myeloablative conditioning regimens, while Flu/Mel and Flu/Bu2 are reduced intensity conditioning regimens. |
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GVHD Prophylaxis
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Tacrolimus / Methotrexate |
110 81.5%
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112 81.8%
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222 81.6%
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Cyclosporine / Methotrexate |
3 2.2%
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3 2.2%
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6 2.2%
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TAC / Mycophenolate mofetil |
8 5.9%
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5 3.6%
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13 4.8%
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Cyclosporine / Mycophenolate mofetil |
1 0.7%
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0 0.0%
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1 0.4%
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Sirolimus / Tacrolimus |
10 7.4%
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12 8.8%
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22 8.1%
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Other |
3 2.2%
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5 3.6%
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8 2.9%
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[1]
Measure Description: Prophylaxis for Graft Versus Host Disease
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ATG Use
[1] Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Yes |
18 13.3%
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22 16.1%
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40 14.7%
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No |
117 86.7%
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115 83.9%
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232 85.3%
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[1]
Measure Description: Use of Anti-Thymocyte Globulin
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Donor Type
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Matched Related |
57 42.2%
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58 42.3%
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115 42.3%
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Mismatched Related |
2 1.5%
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5 3.6%
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7 2.6%
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Matched Unrelated |
66 48.9%
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58 42.3%
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124 45.6%
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Mismatched Unrelated |
10 7.4%
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16 11.7%
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26 9.6%
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Donor Source
Measure Type: Count of Participants Unit of measure: Participants |
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Number Analyzed | 135 participants | 137 participants | 272 participants | |
Peripheral Blood |
127 94.1%
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123 89.8%
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250 91.9%
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Bone Marrow |
8 5.9%
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14 10.2%
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22 8.1%
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Name/Title: | Adam Mendizabal, PhD |
Organization: | The Emmes Corporation |
Phone: | 301-251-1161 |
EMail: | amendizabal@emmes.com |
Responsible Party: | Medical College of Wisconsin |
ClinicalTrials.gov Identifier: | NCT01339910 |
Other Study ID Numbers: |
BMTCTN0901 U01HL069294 ( U.S. NIH Grant/Contract ) U01HL069294-05 ( U.S. NIH Grant/Contract ) BMT CTN 0901 ( Other Identifier: Blood and Marrow Transplant Clinical Trial Network ) 5U24CA076518 ( U.S. NIH Grant/Contract ) |
First Submitted: | April 20, 2011 |
First Posted: | April 21, 2011 |
Results First Submitted: | March 12, 2018 |
Results First Posted: | May 30, 2018 |
Last Update Posted: | January 4, 2023 |