Reduced Intensity Regimen vs Myeloablative Regimen for Myeloid Leukemia or Myelodysplastic Syndrome (BMT CTN 0901)

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01339910
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Cancer Institute (NCI) (NIH), Blood and Marrow Transplant Clinical Trials Network (Other), National Marrow Donor Program (Other)
• Enrollment: 272
• Locations: 32
• Arms: 2
• Actual Duration (Months): 76.5
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The study is designed as a Phase III, multicenter trial comparing outcomes after allogeneic hematopoietic stem cell transplantation (HCT) for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) between patients receiving myeloablative conditioning (MAC) versus reduced intensity conditioning (RIC) regimens.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myelocytic, Acute	Drug: Fludarabine and Busulfan; Drug: Fludarabine and Melphalan; Drug: Busulfan and Fludarabine; Drug: Busulfan and Cyclophosphamide; Drug: Cyclophosphamide and Total Body Irradiation	Phase 3

Detailed Description

Patients randomized to RIC will receive one of two regimen types: the combination of fludarabine (120-180 mg/m^{2) and busulfan (less than or equal to 8 mg/kg or IV equivalent) (Flu/Bu) or fludarabine (120-180 mg/m}2) and melphalan (less than 150 mg/m^{2) (Flu/Mel). Patient randomized to MAC will receive one of three regimens: busulfan (16 mg/kg oral or 12.8 mg/kg IV equivalent) and cyclophosphamide (120 mg/kg) (Bu/Cy); or, busulfan (16 mg/kg PO or 12.8 mg/kg IV) and fludarabine (120-180 mg/m}2) (Bu/Flu); or, cyclophosphamide (120 mg/kg) and total body irradiation (greater than 1200-1420cGy) (CyTBI). A total of 356 patients (178 to each arm) will be accrued on this study over a period of four years. Patients will be followed for up to 18 months from transplantation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 272 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized, Multi-Center, Phase III Study of Allogeneic Stem Cell Transplantation Comparing Regimen Intensity in Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia (BMT CTN #0901)
• Actual Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Jan 16, 2017
• Actual Study Completion Date: Oct 16, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reduced Intensity Conditioning (RIC) One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan.	Drug: Fludarabine and Busulfan; (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4; Other Names: Fludara and Busulfex ; Drug: Fludarabine and Melphalan; (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2; Other Names: Fludara and Alkeran
Active Comparator: Myeloablative Conditioning Regimen (MAC) One of three different regimens in MAC will be administered; busulfan and fludarabine, busulfan and cyclophosphamide, or cyclophosphamide and total body irradiation.	Drug: Busulfan and Fludarabine; (Bu/Flu) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2); Other Names: Busulfex and Fludara ; Drug: Busulfan and Cyclophosphamide; (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg); Other Names: Busulfex and Cytoxan ; Drug: Cyclophosphamide and Total Body Irradiation; (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg); Other Names: Cytoxan and radiation

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Overall Survival (OS) [18 months post-randomization]

   Overall survival is defined as survival of death from any cause.

Secondary Outcome Measures

1. Percentage of Participants With Relapse-Free Survival (RFS) [18 months post-randomization]

   Relapse-free survival is defined as survival without relapse of the primary disease.

2. Percentage of Participants With Disease Relapse [18 months post-randomization]

   Disease Relapse is defined as relapse of the primary disease.

3. Percentage of Participants With Treatment-related Mortality [18 months post-randomization]

   Treatment-related mortality is defined as death without a previous relapse of the primary disease.

4. Percentage of Participants With Neutrophil and Platelet Engraftment [Days 28 and 60 post-transplant]

   Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter for 3 consecutive measurements on different days. The first of the 3 days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.

5. Number of Participants With Donor Cell Engraftment [Days 28 and 100 and 18 months post-transplant]

   Donor cell engraftment will be assessed by donor-recipient chimerism assays. Full donor chimerism is defined as the presence of at least 95% donor cells as a proportion of the total population in the peripheral blood or bone marrow. Graft rejection is defined as the presence of no more than 5% donor cells as a proportion of the total population. Mixed chimerism is defined as the presence of between 5% and 95% donor cells. Mixed or full donor chimerism will be considered evidence of donor engraftment.

6. Percentage of Participants With Acute Graft Versus Host Disease (GVHD) [Day 100 post-transplant]

   Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)*: 0: <2 mg/dL 2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL GI stage*: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4

7. Percentage of Participants With Chronic GVHD [18 months post-transplant]

   Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.

8. Number of Participants With Chronic GVHD Severity [18 months post-transplant]

   Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.

9. Number of Participants With Primary Graft Failure [28 days post-transplant]

   Primary graft failure is defined by lack of neutrophil engraftment.

10. Number of Participants With Secondary Graft Failure [18 months post-transplant]

    Secondary graft failure is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts to less than 500x10^6/liter that is unresponsive to growth factor therapy.

11. Number of Participants With Maximum Grade 3-5 Toxicities [18 months]

    The maximum grade of toxicities reported by participants over the study duration are tabulated. Per the CTCAE criteria, toxicities are graded on a scale of 0-5, with higher numbers indicating greater severity. The categories correspond as follows: 3 - severe; 4 - life-threatening; 5 - fatal

12. Infection Type [18 months post-transplant]

    The number and types of infection events reported are tabulated.

13. Number of Participants With Infections [18 months post-transplant]

    The maximum severity of infections reported by participants are tabulated. The number of infections and the number of patients experiencing infections will be tabulated by type of infection, severity, and time period after transplant. The cumulative incidence of severe, life-threatening, or fatal infections will be compared between the two treatment arms at 6, 12, and 18 months from transplant or until death.

14. Number of Participants With Cause of Death [18 months post-randomization]

    Primary cause of death was adjudicated using previously described criteria (Copelan et al. 2007). When relapse occurred, it was considered the primary cause of death regardless of other events.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age equal or less than 65 years old and equal to or greater than 18 years old.

• Patients with the diagnosis of MDS or AML with fewer than 5% myeloblasts in the bone marrow and no leukemic myeloblasts in the peripheral blood on morphologic analysis performed within 30 days of start of the conditioning regimen enrollment.

• For patients receiving treatment of their MDS or AML prior to transplantation: a)Interval between the start of the most recent cycle of conventional cytotoxic chemotherapy and enrollment must be at least 30 days; b)Interval between completing treatment with a hypomethylating agent or other non-cytotoxic chemotherapy and enrollment must be at least 10 days.

• Patients must have a related or unrelated bone marrow or peripheral blood donor who is human leukocyte antigen (HLA)-matched at 7 or 8 of 8 HLA-A, -B, -C and -DRB1 at high resolution using DNA-based typing.

• HCT-Specific Comorbidity Index Score (HCT-CI) less than or equal to 4.

• Organ function: a) Cardiac function: Ejection fraction greater than or equal to 40%;

1. Hepatic function: total bilirubin less than or equal to 2 times the upper limit of normal and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 3 times the upper limit of normal.; c)Pulmonary function: Diffusing capacity of the lung for carbon monoxide (DLCO) greater than or equal to 40% and forced expiratory volume in one second (FEV1) greater than or equal to 50% (corrected for hemoglobin).

• Creatinine clearance greater than or equal to 50mL/min based on the Cockcroft-Gault formula.

• Signed informed consent.

Exclusion Criteria:

• Prior allograft or prior autograft.

• Symptomatic coronary artery disease.

• Leukemia involvement in the central nervous system (CNS) within 4 weeks of enrollment for patients with a history of prior CNS leukemia involvement (i.e., leukemic blasts previously detected in the cerebral spinal fluid).

• Karnofsky Performance Score less than 70.

• Patients receiving supplemental oxygen.

• Planned use of donor lymphocyte infusion (DLI) therapy.

• Patients with uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms).

• Patients seropositive for the human immunodeficiency virus (HIV).

• Patients with prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent greater than 5 years previously. Cancer treated with curative intent less than 5 years previously will not be allowed unless approved by the Protocol Officer or one of the Protocol Chairs.

• Females who are pregnant or breastfeeding.

• Fertile men and women unwilling to use contraceptive techniques during and for 12 months following treatment.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Phoenix	Phoenix	Arizona	United States	85054
2	University of California, San Diego Medical Center	La Jolla	California	United States	92093
3	University of Florida College of Medicine	Gainesville	Florida	United States	32610-0277
4	Florida Hospital Cancer Institute	Orlando	Florida	United States	32804
5	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33624
6	Emory University	Atlanta	Georgia	United States	30322
7	Blood and Marrow Transplant Program at Northside Hospital	Atlanta	Georgia	United States	30342
8	University of Kansas	Kansas City	Kansas	United States	66160
9	University of Kentucky	Lexington	Kentucky	United States	40536
10	DFCI, Brigham & Women's Hospital	Boston	Massachusetts	United States	02114
11	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
12	University of Minnesota	Minneapolis	Minnesota	United States	55455
13	Mayo Clinic Rochester	Rochester	Minnesota	United States	55095
14	Washington University/Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
15	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
16	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
17	Mount Sinai Medical Center	New York	New York	United States	10029
18	University of Rochester Medical Center	Rochester	New York	United States	14642
19	University of North Carolina Hospital at Chapel Hill	Chapel Hill	North Carolina	United States	27599
20	Duke University Medical Center	Durham	North Carolina	United States	27705
21	Jewish Hospital BMT Program	Cincinnati	Ohio	United States	45236
22	University Hospitals of Cleveland/Case Western	Cleveland	Ohio	United States	44106-5061
23	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
24	Oregon Health & Science University	Portland	Oregon	United States	97239-3098
25	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
26	Baylor University Medical Center	Dallas	Texas	United States	75246
27	Texas Transplant Institute	San Antonio	Texas	United States	78229
28	Utah BMT/University of Utah Medical School	Salt Lake City	Utah	United States	84132
29	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
30	West Virginia University Hospital	Morgantown	West Virginia	United States	26506
31	University of Wisconsin Hospital & Clinics	Madison	Wisconsin	United States	53792-5156
32	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53211

Sponsors and Collaborators

• Medical College of Wisconsin
• National Heart, Lung, and Blood Institute (NHLBI)
• National Cancer Institute (NCI)
• Blood and Marrow Transplant Clinical Trials Network
• National Marrow Donor Program

Investigators

• Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Blood and Marrow Transplant Clinical Trials Network
• National Marrow Donor Program

Publications

• Copelan E, Casper JT, Carter SL, van Burik JA, Hurd D, Mendizabal AM, Wagner JE, Yanovich S, Kernan NA. A scheme for defining cause of death and its application in the T cell depletion trial. Biol Blood Marrow Transplant. 2007 Dec;13(12):1469-76.
• Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005 Dec;11(12):945-56.
• Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005 Oct 15;106(8):2912-9. Epub 2005 Jun 30.
• Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, Harris NL, Le Beau MM, Hellström-Lindberg E, Tefferi A, Bloomfield CD. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009 Jul 30;114(5):937-51. doi: 10.1182/blood-2009-03-209262. Epub 2009 Apr 8. Review.

• Responsible Party: Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT01339910
• Other Study ID Numbers: BMTCTN0901; U01HL069294; U01HL069294-05; BMT CTN 0901; 5U24CA076518
• First Posted: Apr 21, 2011
• Last Update Posted: May 30, 2018
• Last Verified: May 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Medical College of Wisconsin: Acute Myelogenous Leukemia; Myelodysplastic Syndrome
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Preleukemia; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Vidarabine; Cyclophosphamide; Melphalan; Busulfan; Fludarabine; Fludarabine phosphate

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between June 2011 and April 2014 from 32 transplant centers

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Period Title: Overall Study
STARTED	135	137
COMPLETED	132	133
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)	Total
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2	Total of all reporting groups
Overall Participants	135	137	272
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	54.8	54.8	54.8
Sex: Female, Male (Count of Participants)
Female	59 43.7%	70 51.1%	129 47.4%
Male	76 56.3%	67 48.9%	143 52.6%
Primary Disease (Count of Participants)
Acute Myeloid Leukemia (AML)	108 80%	110 80.3%	218 80.1%
Myelodysplastic Syndrome (MDS)	27 20%	27 19.7%	54 19.9%
MDS WHO Classification (Count of Participants)
RA/RARS/RCMD/RCMD-RS/Del-5q/MDS-U	16 11.9%	17 12.4%	33 12.1%
RAEB-1	5 3.7%	5 3.6%	10 3.7%
RAEB-2	6 4.4%	5 3.6%	11 4%
AML WHO Classification (Count of Participants)
AML with recurrent genetic abnormalities	12 8.9%	20 14.6%	32 11.8%
AML with multilineage dysplasia	8 5.9%	12 8.8%	20 7.4%
AML and MDS, therapy related	2 1.5%	3 2.2%	5 1.8%
AML, not otherwise specified	86 63.7%	75 54.7%	161 59.2%
Disease Duration (months) [Median (Full Range) ]
Median (Full Range) [months]	6	6	6
Disease Risk Status (Count of Participants)
Standard	74 54.8%	71 51.8%	145 53.3%
High	54 40%	61 44.5%	115 42.3%
Unknown	7 5.2%	5 3.6%	12 4.4%
HCT-CI (Count of Participants)
0	46 34.1%	40 29.2%	86 31.6%
1-2	45 33.3%	52 38%	97 35.7%
3 or more	42 31.1%	44 32.1%	86 31.6%
Unknown	2 1.5%	1 0.7%	3 1.1%
Conditioning Regimen (Count of Participants)
Flu/Bu4	87 64.4%	0 0%	87 32%
Bu/Cy	40 29.6%	0 0%	40 14.7%
Cy/TBI	8 5.9%	0 0%	8 2.9%
Flu/Mel	0 0%	27 19.7%	27 9.9%
Flu/Bu2	0 0%	110 80.3%	110 40.4%
GVHD Prophylaxis (Count of Participants)
Tacrolimus / Methotrexate	110 81.5%	112 81.8%	222 81.6%
Cyclosporine / Methotrexate	3 2.2%	3 2.2%	6 2.2%
TAC / Mycophenolate mofetil	8 5.9%	5 3.6%	13 4.8%
Cyclosporine / Mycophenolate mofetil	1 0.7%	0 0%	1 0.4%
Sirolimus / Tacrolimus	10 7.4%	12 8.8%	22 8.1%
Other	3 2.2%	5 3.6%	8 2.9%
ATG Use (Count of Participants)
Yes	18 13.3%	22 16.1%	40 14.7%
No	117 86.7%	115 83.9%	232 85.3%
Donor Type (Count of Participants)
Matched Related	57 42.2%	58 42.3%	115 42.3%
Mismatched Related	2 1.5%	5 3.6%	7 2.6%
Matched Unrelated	66 48.9%	58 42.3%	124 45.6%
Mismatched Unrelated	10 7.4%	16 11.7%	26 9.6%
Donor Source (Count of Participants)
Peripheral Blood	127 94.1%	123 89.8%	250 91.9%
Bone Marrow	8 5.9%	14 10.2%	22 8.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Overall Survival (OS)
Description	Overall survival is defined as survival of death from any cause.
Time Frame	18 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	135	137
Number (95% Confidence Interval) [percentage]	77.5	67.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in overall survival at 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. 18 month overall survival was compared between treatment arms using the difference in Kaplan-Meier estimators, which should be close to 0 under the null hypothesis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.07
	Comments	This final test was performed at a 0.049 significance level, since 0.001 was spent at interim analyses and the overall significance level was 0.050.
	Method	Difference in Kaplan-Meier estimators
	Comments
Method of Estimation	Estimation Parameter	Difference in 18 month OS (MAC-RIC)
	Estimated Value	9.8
	Confidence Interval	(2-Sided) 95%; -0.8 to 20.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With Relapse-Free Survival (RFS)
Description	Relapse-free survival is defined as survival without relapse of the primary disease.
Time Frame	18 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	135	137
Number (95% Confidence Interval) [percentage]	67.8	47.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in relapse-free survival at 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. 18 month relapse-free survival was compared between treatment arms using the difference in Kaplan-Meier estimators, which should be close to 0 under the null hypothesis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.01
	Comments	Test performed at a significance level of 0.05
	Method	Difference in Kaplan-Meier estimators
	Comments
Method of Estimation	Estimation Parameter	Difference in 18 month RFS (MAC-RIC)
	Estimated Value	20.4
	Confidence Interval	(2-Sided) 95%; 8.9 to 32.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Disease Relapse
Description	Disease Relapse is defined as relapse of the primary disease.
Time Frame	18 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	135	137
Number (95% Confidence Interval) [percentage]	13.5	48.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the cumulative incidence of disease relapse during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of disease relapse was compared between treatment arms using Gray's test, treating death as a competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.001
	Comments	Test performed at a significance level of 0.05
	Method	Gray's test
	Comments

4. Secondary Outcome

Title	Percentage of Participants With Treatment-related Mortality
Description	Treatment-related mortality is defined as death without a previous relapse of the primary disease.
Time Frame	18 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	135	137
Number (95% Confidence Interval) [percentage]	15.8	4.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the cumulative incidence of treatment-related mortality during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of treatment-related mortality was compared between treatment arms using Gray's test, treating disease relapse as a competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Test performed at a significance level of 0.05
	Method	Gray's test
	Comments

5. Secondary Outcome

Title	Percentage of Participants With Neutrophil and Platelet Engraftment
Description	Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10^6/liter for 3 consecutive measurements on different days. The first of the 3 days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 20,000/microliter for consecutive measurements over 7 days without requiring platelet transfusions. The first of the 7 days will be designated the day of platelet engraftment. Subjects must not have had platelet transfusions during the preceding 7 days.
Time Frame	Days 28 and 60 post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
Neutrophil Engraftment at Day 28	98.5	97.8
Platelet Engraftment at Day 60	95.5	96.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the cumulative incidence of neutrophil engraftment at Day 28 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of neutrophil engraftment at Day 28 was compared between treatment arms using the difference in Aalen-Johansen estimators, which should be close to 0 under the null hypothesis. Death was treated as a competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Test performed at a significance level of 0.05
	Method	Difference in Aalen-Johansen estimators
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the cumulative incidence of platelet engraftment at Day 60 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of platelet engraftment at Day 60 was compared between treatment arms using the difference in Aalen-Johansen estimators, which should be close to 0 under the null hypothesis. Death was treated as a competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.065
	Comments	Test performed at a significance level of 0.05
	Method	Difference in Aalen-Johansen estimators
	Comments

6. Secondary Outcome

Title	Number of Participants With Donor Cell Engraftment
Description	Donor cell engraftment will be assessed by donor-recipient chimerism assays. Full donor chimerism is defined as the presence of at least 95% donor cells as a proportion of the total population in the peripheral blood or bone marrow. Graft rejection is defined as the presence of no more than 5% donor cells as a proportion of the total population. Mixed chimerism is defined as the presence of between 5% and 95% donor cells. Mixed or full donor chimerism will be considered evidence of donor engraftment.
Time Frame	Days 28 and 100 and 18 months post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
Full Donor Chimerism	86 63.7%	80 58.4%
Mixed Chimerism	9 6.7%	30 21.9%
Graft Rejection	1 0.7%	1 0.7%
Death Prior to Assessment	0 0%	0 0%
Unknown (relapsed or missing assay)	36 26.7%	22 16.1%
Full Donor Chimerism	106 78.5%	86 62.8%
Mixed Chimerism	12 8.9%	30 21.9%
Graft Rejection	2 1.5%	1 0.7%
Death Prior to Assessment	6 4.4%	8 5.8%
Unknown (relapsed or missing assay)	6 4.4%	8 5.8%
Full Donor Chimerism	71 52.6%	66 48.2%
Mixed Chimerism	4 3%	5 3.6%
Graft Rejection	1 0.7%	1 0.7%
Death Prior to Assessment	31 23%	42 30.7%
Unknown (relapsed or missing assay)	25 18.5%	19 13.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the proportions of participants with full chimerism, mixed chimerism, graft rejection, and death prior to assessment at Day 28 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments	Test performed at a significance level of 0.05
	Method	Chi-squared
	Comments	3 degrees of freedom

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the proportions of participants with full chimerism, mixed chimerism, graft rejection, and death prior to assessment at Day 100 post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.011
	Comments	Test performed at a significance level of 0.05
	Method	Chi-squared
	Comments	3 degrees of freedom

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the proportions of participants with full chimerism, mixed chimerism, graft rejection, and death prior to assessment at 18 months post-transplant between AML/MDS participants receiving MAC and RIC conditioning regimens.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments	Test performed at a significance level of 0.05
	Method	Chi-squared
	Comments	3 degrees of freedom

7. Secondary Outcome

Title	Percentage of Participants With Acute Graft Versus Host Disease (GVHD)
Description	Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash Rash <25% of body surface area Rash on 25-50% of body surface area Rash on > 50% of body surface area Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)*: 0: <2 mg/dL 2-3 mg/dL 3.01-6 mg/dL 6.01-15.0 mg/dL >15 mg/dL GI stage*: 0: No diarrhea or diarrhea <500 mL/day Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD Diarrhea 1000-1499 mL/day Diarrhea >1500 mL/day Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1. GVHD grade: 0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
Time Frame	Day 100 post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
Grade II-IV Acute GVHD	44.7	31.6
Grade III-IV Acute GVHD	13.6	6.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the cumulative incidence of grade II-IV acute GVHD during the first 100 days post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of grade II-IV acute GVHD was compared between treatment arms using Gray's test, treating death as a competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments	Test performed at a significance level of 0.05
	Method	Gray's test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the cumulative incidence of grade III-IV acute GVHD during the first 100 days post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of grade III-IV acute GVHD was compared between treatment arms using Gray's test, treating death as a competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments	Test performed at a significance level of 0.05
	Method	Gray's test
	Comments

8. Secondary Outcome

Title	Percentage of Participants With Chronic GVHD
Description	Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe. Occurrence of chronic GVHD is defined as the occurrence of mild, moderate, or severe chronic GVHD per this classification.
Time Frame	18 months post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
Number (95% Confidence Interval) [percentage]	64.0	47.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Myeloablative Conditioning Regimen (MAC), Reduced Intensity Conditioning (RIC)
	Comments	The null hypothesis is that there is no difference in the cumulative incidence of chronic GVHD during the first 18 months post-randomization between AML/MDS participants receiving MAC and RIC conditioning regimens. Cumulative incidence of chronic GVHD was compared between treatment arms using Gray's test, treating death as a competing risk.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments	Test performed at a significance level of 0.05
	Method	Gray's test
	Comments

9. Secondary Outcome

Title	Number of Participants With Chronic GVHD Severity
Description	Chronic GVHD is classified per 2005 NIH Consensus Criteria (Filipovich et al. 2005) into categories of severity: none, mild, moderate, and severe.
Time Frame	18 months post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
None	47 34.8%	70 51.1%
Mild	40 29.6%	34 24.8%
Moderate	33 24.4%	17 12.4%
Severe	12 8.9%	12 8.8%

10. Secondary Outcome

Title	Number of Participants With Primary Graft Failure
Description	Primary graft failure is defined by lack of neutrophil engraftment.
Time Frame	28 days post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
Count of Participants [Participants]	1 0.7%	3 2.2%

11. Secondary Outcome

Title	Number of Participants With Secondary Graft Failure
Description	Secondary graft failure is defined by initial neutrophil engraftment followed by subsequent decline in neutrophil counts to less than 500x10^6/liter that is unresponsive to growth factor therapy.
Time Frame	18 months post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
Count of Participants [Participants]	1 0.7%	4 2.9%

12. Secondary Outcome

Title	Number of Participants With Maximum Grade 3-5 Toxicities
Description	The maximum grade of toxicities reported by participants over the study duration are tabulated. Per the CTCAE criteria, toxicities are graded on a scale of 0-5, with higher numbers indicating greater severity. The categories correspond as follows: 3 - severe; 4 - life-threatening; 5 - fatal
Time Frame	18 months

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
0-2	34 25.2%	59 43.1%
3	66 48.9%	47 34.3%
4	22 16.3%	18 13.1%
5	10 7.4%	9 6.6%

13. Secondary Outcome

Title	Infection Type
Description	The number and types of infection events reported are tabulated.
Time Frame	18 months post-transplant

Outcome Measure Data

Analysis Population Description

Infection events

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
Measure Infection events	353	283
Bacterial	192	161
Viral	117	95
Fungal	37	12
Protozoal	1	0
Other	6	15

14. Secondary Outcome

Title	Number of Participants With Infections
Description	The maximum severity of infections reported by participants are tabulated. The number of infections and the number of patients experiencing infections will be tabulated by type of infection, severity, and time period after transplant. The cumulative incidence of severe, life-threatening, or fatal infections will be compared between the two treatment arms at 6, 12, and 18 months from transplant or until death.
Time Frame	18 months post-transplant

Outcome Measure Data

Analysis Population Description

Transplanted participants

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	132	133
None	38 28.1%	43 31.4%
Moderate	42 31.1%	37 27%
Severe	40 29.6%	43 31.4%
Life Threatening or Fatal	12 8.9%	10 7.3%

15. Secondary Outcome

Title	Number of Participants With Cause of Death
Description	Primary cause of death was adjudicated using previously described criteria (Copelan et al. 2007). When relapse occurred, it was considered the primary cause of death regardless of other events.
Time Frame	18 months post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Myeloablative Conditioning Regimen (MAC)	Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)	One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
Measure Participants	135	137
Relapse	10 7.4%	38 27.7%
Organ failure	3 2.2%	1 0.7%
GVHD	15 11.1%	4 2.9%
Infection	2 1.5%	0 0%
Sudden death	0 0%	1 0.7%
Still alive	105 77.8%	93 67.9%

Adverse Events

Time Frame	18 months post-randomization
Adverse Event Reporting Description	Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grade 3-5 AEs were required to be reported through the AE system per protocol.
Arm/Group Title	Myeloablative Conditioning Regimen (MAC)		Reduced Intensity Conditioning (RIC)
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: 4 mg/kg/day PO, 3.2 mg/kg/day IV or mg/m^2/day with Bu Css 900±100 ng/mL (total dose of 16 mg/kg, 12.8 mg/kg or 520 mg/m^2, respectively) on Days -5 to -2 Fludarabine: 30 mg/m^2/day on Days -5 to -2: Flu (total dose of 120 mg/m^2) Busulfan and Cyclophosphamide: (Bu/Cy) Busulfan: 4 mg/kg/day PO, 3.2 mg/kg/day IV or 130 mg/m^2/day with Bu Css 900 ± 100 ng/mL (total dose of 16 mg/kg or 12.8 mg/kg or 520 mg/m^2, respectively) on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg) Cyclophosphamide and Total Body Irradiation: (Cy/TBI) TBI: 1200-1420 cGy on Days -7 to -4 Cyclophosphamide: 60 mg/kg/day on Days -3 to -2 (total dose of 120 mg/kg)		One of two different regimens in RIC will be administered; fludarabine and busulfan, or fludarabine and melphalan. Fludarabine and Busulfan: (Flu/Bu) Fludarabine: 30 mg/m^2/day on Days -6 to -2 (total dose of 150 mg/m^2) Busulfan: 4 mg/kg/day PO or 3.2 mg/kg/day (total dose of 8 mg/kg or 6.4 mg/kg, respectively) on Days -5 to -4 Fludarabine and Melphalan: (Flu/Mel) Fludarabine: 30 mg/m^2/day on Days -5 to -2 (total dose of 120 mg/m^2) Melphalan: 140 mg/m^2 on Day -2
All Cause Mortality
	Myeloablative Conditioning Regimen (MAC)		Reduced Intensity Conditioning (RIC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Myeloablative Conditioning Regimen (MAC)		Reduced Intensity Conditioning (RIC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/132 (15.9%)		16/133 (12%)
Blood and lymphatic system disorders
Autoimmune haemolytic anaemia	1/132 (0.8%)	1	0/133 (0%)	0
Immune thrombocytopenic purpura	1/132 (0.8%)	1	0/133 (0%)	0
Cardiac disorders
Acute myocardial infarction	1/132 (0.8%)	1	1/133 (0.8%)	1
Atrial fibrillation	1/132 (0.8%)	1	0/133 (0%)	0
Cardiac arrest	0/132 (0%)	0	1/133 (0.8%)	1
Pericardial effusion	1/132 (0.8%)	1	1/133 (0.8%)	1
Supraventricular tachycardia	1/132 (0.8%)	1	0/133 (0%)	0
Eye disorders
Vision blurred	1/132 (0.8%)	1	0/133 (0%)	0
Gastrointestinal disorders
Gastrointestinal haemorrhage	1/132 (0.8%)	1	1/133 (0.8%)	1
Oesophagitis	0/132 (0%)	0	1/133 (0.8%)	1
Pancreatitis	0/132 (0%)	0	1/133 (0.8%)	1
Hepatobiliary disorders
Hepatic haemorrhage	1/132 (0.8%)	1	0/133 (0%)	0
Hyperbilirubinaemia	0/132 (0%)	0	1/133 (0.8%)	1
Immune system disorders
Graft versus host disease	1/132 (0.8%)	1	0/133 (0%)	0
Infections and infestations
Device related infection	1/132 (0.8%)	1	0/133 (0%)	0
Enterocolitis infectious	1/132 (0.8%)	1	0/133 (0%)	0
Respiratory tract infection	1/132 (0.8%)	1	0/133 (0%)	0
Injury, poisoning and procedural complications
Fall	0/132 (0%)	0	1/133 (0.8%)	1
Hip fracture	1/132 (0.8%)	1	0/133 (0%)	0
Spinal compression fracture	0/132 (0%)	0	1/133 (0.8%)	1
Spinal fracture	0/132 (0%)	0	1/133 (0.8%)	1
Investigations
Blood bilirubin increased	0/132 (0%)	0	1/133 (0.8%)	1
Liver function test increased	0/132 (0%)	0	1/133 (0.8%)	1
Metabolism and nutrition disorders
Gout	0/132 (0%)	0	1/133 (0.8%)	1
Musculoskeletal and connective tissue disorders
Back pain	0/132 (0%)	0	2/133 (1.5%)	2
Flank pain	1/132 (0.8%)	1	0/133 (0%)	0
Nervous system disorders
Haemorrhage intracranial	1/132 (0.8%)	1	0/133 (0%)	0
Posterior reversible encephalopathy syndrome	1/132 (0.8%)	1	0/133 (0%)	0
Syncope	2/132 (1.5%)	2	0/133 (0%)	0
Vocal cord paralysis	0/132 (0%)	0	1/133 (0.8%)	1
Psychiatric disorders
Mental status changes	1/132 (0.8%)	1	0/133 (0%)	0
Renal and urinary disorders
Hydronephrosis	0/132 (0%)	0	1/133 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	1/132 (0.8%)	1	0/133 (0%)	0
Dyspnoea at rest	1/132 (0.8%)	1	0/133 (0%)	0
Pulmonary embolism	4/132 (3%)	4	1/133 (0.8%)	1
Respiratory distress	0/132 (0%)	0	1/133 (0.8%)	1
Respiratory failure	2/132 (1.5%)	2	1/133 (0.8%)	1
Skin and subcutaneous tissue disorders
Stevens-Johnson syndrome	0/132 (0%)	0	1/133 (0.8%)	1
Surgical and medical procedures
Cholecystectomy	2/132 (1.5%)	2	0/133 (0%)	0
Finger amputation	0/132 (0%)	0	1/133 (0.8%)	1
Prostatectomy	0/132 (0%)	0	1/133 (0.8%)	1
Vascular disorders
Embolism	1/132 (0.8%)	2	0/133 (0%)	0
Hypotension	0/132 (0%)	0	2/133 (1.5%)	2
Venoocclusive disease	1/132 (0.8%)	1	0/133 (0%)	0
Other (Not Including Serious) Adverse Events
	Myeloablative Conditioning Regimen (MAC)		Reduced Intensity Conditioning (RIC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/132 (5.3%)		4/133 (3%)
General disorders
Chest pain	1/132 (0.8%)	1	0/133 (0%)	0
Investigations
Weight decreased	2/132 (1.5%)	2	1/133 (0.8%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/132 (0.8%)	1	0/133 (0%)	0
Musculoskeletal pain	1/132 (0.8%)	1	0/133 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large granular lymphocytosis	1/132 (0.8%)	1	1/133 (0.8%)	1
Nervous system disorders
Syncope	1/132 (0.8%)	1	0/133 (0%)	0
Psychiatric disorders
Mania	0/132 (0%)	0	1/133 (0.8%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/132 (0.8%)	1	0/133 (0%)	0
Surgical and medical procedures
Hernia repair	0/132 (0%)	0	1/133 (0.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.