Acute Myeloid Leukemia (AML), Hematopoietic Stem Cell Transplant (HSCT), Myelodysplastic Syndrome (MDS)
Conditions
Brief summary
The purpose of this study is to compare safety and efficacy of reduced-intensity conditioning and myeloablative conditioning regimens prior to HSCT in high-risk AML/MDS pediatric and young adult patients. This study investigates the use of two novel conditioning therapies for hematopoietic stem cell transplant (HSCT). The primary focus of both the investigators' myeloablative and reduced-intensity conditioning regimens is to reduce overall toxicity so that pediatric and young adult patients with high-risk AML/MDS with significant pretransplant comorbidities who would have been ineligible to proceed to HSCT previously can now receive potentially life-saving treatment.
Interventions
DRUGReduced-Intensity Conditioning Regimen
Campath (alemtuzumab) - drug class: monoclonal antibody Droxia (hydroxyurea) - drug class: antimetabolite Fludara (fludarabine) - drug class: antimetabolite Alkeran (melphalan) - drug class: alkylating agent Thiotepa (triethylenethiophosphoramide) - drug class: cytotoxic agent
Campath (alemtuzumab) - drug class: monoclonal antibody Thiotepa (triethylenethiophosphoramide) - drug class: cytotoxic agent Fludara (fludarabine) - drug class: antimetabolite Busulfex (busulfan) - drug class: alkylating agent
Sponsors
Randy Windreich
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Months to 26 Years
Healthy volunteers
No
Inclusion criteria
Individuals must meet all the following criteria to be eligible for this study. * Subject, parent, or legal guardian, if applicable, must have given written informed consent. For patients ≤ 17 years of age who are developmentally able, assent or affirmation will be obtained. * Age 0-26, inclusive, at time of consent. * Diagnosis of myelodysplastic syndrome or acute myeloid leukemia, either high-risk (defined below), relapsed or primary refractory, MRD-positive without circulating myeloblasts or active extramedullary disease at the time of transplant. Active marrow disease is permitted. High-risk AML features are defined by the following: RAM phenotype; adverse cytogenetic abnormalities of monosomy 5, monosomy 7, 5q deletion, or other unfavorable prognostic markers according to cytogenetics, FISH, or next generation sequencing (NGS); presence of FLT3 positive internal tandem duplication (FLT3/ITD+), particularly high allelic ratio; treatment-related AML; or positive minimal residual disease (MRD) at end of Induction I. * Stem cell sources include bone marrow, peripheral blood stem cells, or umbilical cord blood. Related bone marrow, peripheral blood stem cell, or cord blood unit: sibling should be HLA-matched at A, B, and DR-B1 loci. Unrelated cord blood unit should be at a minimum of 4/6 matched at antigen level on HLA A and B, and allele level at HLA DR-B1 loci. Unrelated bone marrow or peripheral blood stem cell donor should be HLA allele level matched at DR-B1. * Minimum pre-freezing cell dose for cord blood units: 3 x 10\^7 total nucleated cells/kg and 1.5 x 10\^5 CD34+ cells/kg. If this is not attainable, then double cord blood transplant should be considered. * Subject must have adequate performance status: Lansky score ≥60% for patients \<16 years, Karnofsky score ≥60% for patients ≥16 years. * Subject must have adequate pre-transplant organ function to undergo one of the two conditioning regimens, either the myeloablative conditioning (MAC) OR reduced-intensity conditioning (RIC) regimen. If a subject does not meet the following organ function criteria for the MAC regimen, the RIC regimen will be considered if eligibility criteria is met. The RIC regimen may also be considered, regardless of MAC eligibility, if deemed appropriate by the Principal Investigator and/or treating physician. Pre-transplant organ function criteria for Myeloablative Conditioning regimen: * Renal: creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2. * Hepatic: total bilirubin ≤2.0 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline Phosphatase \<4 x upper limit of normal (ULN) for age. * Cardiac: normal cardiac function by echocardiogram or radionuclide scan, as defined by left ventricular ejection fraction at rest \>45% or shortening fraction \>26%. * Pulmonary: FEV1, FVC, and DLCO (corrected for hemoglobin) ≥50% of predicted; if unable to perform pulmonary function tests, then oxygen saturation ≥92% on room air. OR Pre-transplant organ function criteria for Reduced-Intensity Conditioning regimen: * Renal: creatinine clearance or radioisotope GFR ≥70 mL/min/1.73 m2. * Hepatic: total bilirubin ≤2.5 mg/dL unless the increase in bilirubin is attributable to Gilbert's syndrome; and SGOT (AST), SGPT (ALT), and Alkaline Phosphatase \<5 x upper limit of normal (ULN) for age. * Cardiac: normal cardiac function by echocardiogram or radionuclide scan, as defined by left ventricular ejection fraction at rest \>40% or shortening fraction \>26%. * Pulmonary: FEV1, FVC, and DLCO (corrected for hemoglobin) ≥40% of predicted; if unable to perform pulmonary function tests, then oxygen saturation ≥92% on room air. * HIV and HTLV negative, by either PCR or serology. * Negative pregnancy test for females ≥10 years old or who have reached menarche. * All females of childbearing potential and sexually active males must agree to use an FDA approved method of birth control for up to 12 months after HSCT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect.
Exclusion criteria
Individuals who meet any of the following criteria are not eligible for this protocol. * Uncontrolled bacterial, viral, fungal, or other infection at the time of cytoreduction, defined by positive blood cultures and/or fevers \>38.0 within 24 hours of start of conditioning therapy. * Females who are pregnant or who are lactating. * Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study. Additional
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Preliminary Efficacy (Event-free Survival at 6 Months) in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | 6 months | Event-free survival at 6 months, where events are defined as relapse or death |
| Number of Non-relapsed Deaths by 6 Months Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | Day 180 | Number of non-relapsed deaths that occur |
| Number of Non-relapsed Deaths by 100 Days Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | Day 100 | Number of non-relapsed deaths that occur |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Pace of Platelet Recovery | Day of transplant to end of study (Day 365) | Platelet Engraftment (the first of three consecutive days in which the platelet count exceeded 20,000/mm3 without platelet transfusions for the preceding 7 days) |
| Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | Day of transplant to end of study (Day 365) | Grade 0: no stage 1-4 of any organ. Grade I: stage 1-2 skin rash (stage 1: \<25%, stage 2: 25-50% body surface area affected by maculopapular rash), no gut or liver involvement. Grade II: stage 3 skin rash (\>50% body surface area affected), or stage 1 GI involvement (10-19.9 mL/kg/day volume of diarrhea), or stage 1 liver involvement (2-3 mg/dL total bilirubin level). Grade III: stage 0-3 skin rash with stage 2-4 GI involvement (stage 2: 20-30 mL/kg/day, stage 3: \>30 mL/kg/day volume of diarrhea, stage 4: severe abdominal pain with or without ileus and/or grossly blood stool) or stage 2-3 liver involvement (stage 2: 3-6 mg/dL, stage 3: 6-15 mg/dL total bilirubin level). Grade IV: stage 4 skin rash (generalized erythroderma with bullous formation) or stage 4 liver involvement (\>15 mg/dL total bilirubin level). |
| Day 0 Campath (Alemtuzumab) Level | Day 0 | Campath (Alemtuzumab) level measured on the day of transplant |
| Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Day of transplant to end of study (Day 365) | Limited cGVHD: localized skin involvement and/or hepatic dysfunction due to cGVHD. Extensive cGVHD: one or more of the following: generalized skin involvement; liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis; involvement of eye, minor salivary glands or oral mucosa based on biopsy, or any other target organ. Mild cGVHD: 1 or 2 organs involved with no more than score 1 plus lung score 0. Moderate cGVHD: 3 or more organs involved with no more than score 1, or at least one organ (not lung) with score 2, or lung score 1. Severe cGVHD: at least one organ with score 3, or lung score 2 or 3. |
| Pace of Immune Reconstitution | Day 180 | Immune recovery as measured by lymphocyte subsets |
| Treatment-related Mortality (TRM) | Day 100 and 180 post-transplant | The number of subjects deceased due to transplant-related (i.e. non-relapse) causes |
| Incidence of Primary Graft Failure. | Post-transplant to 42 days post-transplant | The failure to achieve an ANC ≥500/μL after 42 days, determined by three consecutive measurements on different days, and not caused by recurrent leukemia. |
| Incidence of Grades 4 and 5 Adverse Events | Day 180 | Adverse events as assessed by CTCAE |
| Disease-free Survival (DFS) | Day 100 and 180 post-transplant | The number of subjects who are alive without relapse/leukemia |
| The Number of Subjects With Overall Survival (OS) | Day 100 and 180 post-transplant | The number of subjects who are alive |
| The Pace of Neutrophil Recovery | Day of transplant to end of study (Day 365) | Neutrophil Engraftment (the first of three consecutive days in which the absolute neutrophil count (ANC) exceeded 500/mcL) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Reduced-Intensity Conditioning Campath (alemtuzumab), Droxia (hydroxyurea), Fludara (fludarabine), Alkeran (melphalan), Thiotepa (triethylenethiophosphoramide)
Trade Name (generic name)
Reduced-Intensity Conditioning Regimen: Campath (alemtuzumab) - drug class: monoclonal antibody Droxia (hydroxyurea) - drug class: antimetabolite Fludara (fludarabine) - drug class: antimetabolite Alkeran (melphalan) - drug class: alkylating agent Thiotepa (triethylenethiophosphoramide) - drug class: cytotoxic agent | 6 |
| Myeloablative Conditioning Campath (alemtuzumab), Thiotepa (triethylenethiophosphoramide) , Fludara (fludarabine), Busulfex (busulfan)
Trade Name (generic name)
Myeloablative Conditioning Regimen: Campath (alemtuzumab) - drug class: monoclonal antibody Thiotepa (triethylenethiophosphoramide) - drug class: cytotoxic agent Fludara (fludarabine) - drug class: antimetabolite Busulfex (busulfan) - drug class: alkylating agent | 15 |
| Total | 21 |
Baseline characteristics
| Characteristic | Myeloablative Conditioning | Total | Reduced-Intensity Conditioning |
|---|---|---|---|
| Age, Continuous | 8 years | 12.3 years | 17.3 years |
| Diagnosis Acute Myeloid Leukemia (AML) | 10 Participants | 15 Participants | 5 Participants |
| Diagnosis Myelodysplastic syndrome (MDS) | 5 Participants | 6 Participants | 1 Participants |
| Donor Source Sibling donor | 2 Participants | 6 Participants | 4 Participants |
| Donor Source Unrelated donor | 13 Participants | 15 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants | 19 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 18 Participants | 5 Participants |
| Region of Enrollment Puerto Rico | 1 participants | 1 participants | 0 participants |
| Region of Enrollment United States | 14 participants | 20 participants | 6 participants |
| Sex: Female, Male Female | 7 Participants | 9 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 12 Participants | 4 Participants |
| Stem Cell Source Bone Marrow | 5 Participants | 9 Participants | 4 Participants |
| Stem Cell Source Peripheral Blood | 3 Participants | 3 Participants | 0 Participants |
| Stem Cell Source Umbilical Cord Blood | 7 Participants | 9 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 6 | 1 / 15 |
| other Total, other adverse events | 0 / 6 | 0 / 15 |
| serious Total, serious adverse events | 6 / 6 | 15 / 15 |
Outcome results
Primary
Number of Non-relapsed Deaths by 100 Days Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.
Number of non-relapsed deaths that occur
Time frame: Day 100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced-Intensity Conditioning | Number of Non-relapsed Deaths by 100 Days Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | 1 Participants |
| Myeloablative Conditioning | Number of Non-relapsed Deaths by 100 Days Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | 0 Participants |
Primary
Number of Non-relapsed Deaths by 6 Months Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.
Number of non-relapsed deaths that occur
Time frame: Day 180
Population: Analysis population includes only subjects without relapse (i.e. subjects who relapse are therefore excluded from this analysis).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced-Intensity Conditioning | Number of Non-relapsed Deaths by 6 Months Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | 1 Participants |
| Myeloablative Conditioning | Number of Non-relapsed Deaths by 6 Months Post-transplant in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | 0 Participants |
Primary
Preliminary Efficacy (Event-free Survival at 6 Months) in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS.
Event-free survival at 6 months, where events are defined as relapse or death
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced-Intensity Conditioning | Preliminary Efficacy (Event-free Survival at 6 Months) in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | 5 Participants |
| Myeloablative Conditioning | Preliminary Efficacy (Event-free Survival at 6 Months) in Pediatric Patients Receiving a Myeloablative or Reduced-intensity Preparative Regimen Prior to HSCT for High-risk AML and MDS. | 14 Participants |
Secondary
Day 0 Campath (Alemtuzumab) Level
Campath (Alemtuzumab) level measured on the day of transplant
Time frame: Day 0
Population: Only 2 subjects in Reduced-Intensity Conditioning arm and no subjects in Myeloablative Conditioning arm had a Day 0 Campath (Alemtuzumab) level drawn.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced-Intensity Conditioning | Day 0 Campath (Alemtuzumab) Level | 0.24 mcg/mL |
Secondary
Disease-free Survival (DFS)
The number of subjects who are alive without relapse/leukemia
Time frame: Day 100 and 180 post-transplant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced-Intensity Conditioning | Disease-free Survival (DFS) | Day 100 | 5 Participants |
| Reduced-Intensity Conditioning | Disease-free Survival (DFS) | Day 180 | 5 Participants |
| Myeloablative Conditioning | Disease-free Survival (DFS) | Day 100 | 14 Participants |
| Myeloablative Conditioning | Disease-free Survival (DFS) | Day 180 | 14 Participants |
Secondary
Incidence of Grades 4 and 5 Adverse Events
Adverse events as assessed by CTCAE
Time frame: Day 180
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | White blood dell decreased | 6 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Platelet count decreased | 6 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Lymphocyte count decreased | 6 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Neutrophil count decreased | 6 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Sepsis | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Anemia | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Hyperglycemia | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Alkaline phosphatase elevated | 0 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | GGT increased | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Febrile neutropenia | 0 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Pneumonitis | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Pneumothorax | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Bronchopulmonary hemorrhage | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Multi-organ failure | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Cardiac arrest | 1 Participants |
| Reduced-Intensity Conditioning | Incidence of Grades 4 and 5 Adverse Events | Encephalitis infection | 1 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Encephalitis infection | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | White blood dell decreased | 15 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | GGT increased | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Platelet count decreased | 15 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Bronchopulmonary hemorrhage | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Lymphocyte count decreased | 15 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Febrile neutropenia | 1 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Neutrophil count decreased | 12 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Cardiac arrest | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Sepsis | 6 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Pneumonitis | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Anemia | 1 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Multi-organ failure | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Hyperglycemia | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Pneumothorax | 0 Participants |
| Myeloablative Conditioning | Incidence of Grades 4 and 5 Adverse Events | Alkaline phosphatase elevated | 1 Participants |
Secondary
Incidence of Primary Graft Failure.
The failure to achieve an ANC ≥500/μL after 42 days, determined by three consecutive measurements on different days, and not caused by recurrent leukemia.
Time frame: Post-transplant to 42 days post-transplant
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced-Intensity Conditioning | Incidence of Primary Graft Failure. | 0 Participants |
| Myeloablative Conditioning | Incidence of Primary Graft Failure. | 0 Participants |
Secondary
Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade
Grade 0: no stage 1-4 of any organ. Grade I: stage 1-2 skin rash (stage 1: \<25%, stage 2: 25-50% body surface area affected by maculopapular rash), no gut or liver involvement. Grade II: stage 3 skin rash (\>50% body surface area affected), or stage 1 GI involvement (10-19.9 mL/kg/day volume of diarrhea), or stage 1 liver involvement (2-3 mg/dL total bilirubin level). Grade III: stage 0-3 skin rash with stage 2-4 GI involvement (stage 2: 20-30 mL/kg/day, stage 3: \>30 mL/kg/day volume of diarrhea, stage 4: severe abdominal pain with or without ileus and/or grossly blood stool) or stage 2-3 liver involvement (stage 2: 3-6 mg/dL, stage 3: 6-15 mg/dL total bilirubin level). Grade IV: stage 4 skin rash (generalized erythroderma with bullous formation) or stage 4 liver involvement (\>15 mg/dL total bilirubin level).
Time frame: Day of transplant to end of study (Day 365)
Population: Subjects must survive at least until 100 days post-transplant for evaluation for acute graft-versus-host disease, i.e. subjects who die before 100 days post-transplant are not evaluable and therefore excluded from analysis.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced-Intensity Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade I | 2 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade III | 0 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade II | 0 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade IV | 0 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | No aGVHD (Grade 0) | 3 Participants |
| Myeloablative Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade IV | 0 Participants |
| Myeloablative Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | No aGVHD (Grade 0) | 7 Participants |
| Myeloablative Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade I | 3 Participants |
| Myeloablative Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade II | 5 Participants |
| Myeloablative Conditioning | Number of Participants Developing Acute Graft Versus Host Disease (aGVHD) by Grade | aGVHD Grade III | 0 Participants |
Secondary
Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade
Limited cGVHD: localized skin involvement and/or hepatic dysfunction due to cGVHD. Extensive cGVHD: one or more of the following: generalized skin involvement; liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis; involvement of eye, minor salivary glands or oral mucosa based on biopsy, or any other target organ. Mild cGVHD: 1 or 2 organs involved with no more than score 1 plus lung score 0. Moderate cGVHD: 3 or more organs involved with no more than score 1, or at least one organ (not lung) with score 2, or lung score 1. Severe cGVHD: at least one organ with score 3, or lung score 2 or 3.
Time frame: Day of transplant to end of study (Day 365)
Population: Subjects must survive at least until 365 days post-transplant for evaluation for chronic graft-versus-host disease, i.e. subjects who die before 365 days post-transplant are not evaluable and therefore excluded from analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced-Intensity Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | No cGVHD | 3 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Limited cGVHD | 1 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Extensive cGVHD | 1 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Mild cGVHD | 2 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Moderate cGVHD | 0 Participants |
| Reduced-Intensity Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Severe cGVHD | 0 Participants |
| Myeloablative Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Moderate cGVHD | 0 Participants |
| Myeloablative Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | No cGVHD | 8 Participants |
| Myeloablative Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Mild cGVHD | 4 Participants |
| Myeloablative Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Limited cGVHD | 4 Participants |
| Myeloablative Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Severe cGVHD | 1 Participants |
| Myeloablative Conditioning | Number of Participants Developing Chronic Graft Versus Host Disease (cGVHD) by Grade | Extensive cGVHD | 1 Participants |
Secondary
Pace of Immune Reconstitution
Immune recovery as measured by lymphocyte subsets
Time frame: Day 180
Population: One subject in each arm did not survive to Day 180
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Reduced-Intensity Conditioning | Pace of Immune Reconstitution | CD4 Count (Helper T-cell) | 171 cells/mm3 |
| Reduced-Intensity Conditioning | Pace of Immune Reconstitution | CD19 Count (Total B-cells) | 347 cells/mm3 |
| Reduced-Intensity Conditioning | Pace of Immune Reconstitution | CD8 Count (Suppressor T-cells) | 222 cells/mm3 |
| Reduced-Intensity Conditioning | Pace of Immune Reconstitution | CD16/56 Count (Total NK cells) | 359 cells/mm3 |
| Reduced-Intensity Conditioning | Pace of Immune Reconstitution | CD3 Count (Total T-cells) | 405 cells/mm3 |
| Myeloablative Conditioning | Pace of Immune Reconstitution | CD16/56 Count (Total NK cells) | 218 cells/mm3 |
| Myeloablative Conditioning | Pace of Immune Reconstitution | CD4 Count (Helper T-cell) | 199.5 cells/mm3 |
| Myeloablative Conditioning | Pace of Immune Reconstitution | CD3 Count (Total T-cells) | 405 cells/mm3 |
| Myeloablative Conditioning | Pace of Immune Reconstitution | CD19 Count (Total B-cells) | 366.5 cells/mm3 |
| Myeloablative Conditioning | Pace of Immune Reconstitution | CD8 Count (Suppressor T-cells) | 113 cells/mm3 |
Secondary
The Number of Subjects With Overall Survival (OS)
The number of subjects who are alive
Time frame: Day 100 and 180 post-transplant
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced-Intensity Conditioning | The Number of Subjects With Overall Survival (OS) | Day 100 | 5 Participants |
| Reduced-Intensity Conditioning | The Number of Subjects With Overall Survival (OS) | Day 180 | 5 Participants |
| Myeloablative Conditioning | The Number of Subjects With Overall Survival (OS) | Day 100 | 15 Participants |
| Myeloablative Conditioning | The Number of Subjects With Overall Survival (OS) | Day 180 | 14 Participants |
Secondary
The Pace of Neutrophil Recovery
Neutrophil Engraftment (the first of three consecutive days in which the absolute neutrophil count (ANC) exceeded 500/mcL)
Time frame: Day of transplant to end of study (Day 365)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced-Intensity Conditioning | The Pace of Neutrophil Recovery | 13 Days |
| Myeloablative Conditioning | The Pace of Neutrophil Recovery | 13 Days |
Secondary
The Pace of Platelet Recovery
Platelet Engraftment (the first of three consecutive days in which the platelet count exceeded 20,000/mm3 without platelet transfusions for the preceding 7 days)
Time frame: Day of transplant to end of study (Day 365)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced-Intensity Conditioning | The Pace of Platelet Recovery | 38 days |
| Myeloablative Conditioning | The Pace of Platelet Recovery | 32 days |
Secondary
Treatment-related Mortality (TRM)
The number of subjects deceased due to transplant-related (i.e. non-relapse) causes
Time frame: Day 100 and 180 post-transplant
Population: Subjects who die due to transplant-related causes by 100 and 180 days post-transplant, thus subjects who relapse before that time are excluded from analysis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced-Intensity Conditioning | Treatment-related Mortality (TRM) | Day 100 | 1 Participants |
| Reduced-Intensity Conditioning | Treatment-related Mortality (TRM) | Day 180 | 1 Participants |
| Myeloablative Conditioning | Treatment-related Mortality (TRM) | Day 100 | 0 Participants |
| Myeloablative Conditioning | Treatment-related Mortality (TRM) | Day 180 | 0 Participants |