Acute Lymphocytic Leukemia, Acute Myelogenous Leukemia, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome, Natural Killer Cell Lymphoblastic Leukemia/Lymphoma
Conditions
Keywords
Double cord blood
Brief summary
This study is a Phase III, randomized, open-label, multi-center, prospective study of single umbilical cord blood (UCB) transplantation versus double UCB transplantation in pediatric patients with hematologic malignancies.
Detailed description
BACKGROUND: In nearly every large single center or registry analysis of outcomes after UCB transplantation, cell dose is identified as an important factor influencing the incidence and rate of hematopoietic recovery, risk of transplant-related mortality, and probability of survival. Pilot data suggest that infusion of two partially human leukocyte antigen (HLA)-matched UCB units, which always augments the graft cell dose, is safe and may improve neutrophil recovery and survival. To determine whether the infusion of two UCB units enhances survival, a multi-center, open-label, randomized trial is proposed. As adequate single UCB units can be identified for more than 80% of pediatric recipients (in contrast to less than 30% for adults), this study will be open only to pediatric patients. The population will be restricted to patients with high-risk hematologic malignancy, the most common indication of UCB transplantation in children. DESIGN NARRATIVE: Participants will include patients 1 to 21 years of age with a diagnosis of hematological malignancy and with two partially HLA-matched UCB units. Units must be HLA-matched at 3 of 6 HLA-A and B (intermediate resolution molecular typing) and DRB1 (high resolution molecular typing) with each other and 4 of 6 with the recipient. Two appropriately HLA-matched units must be available such that one unit delivers a pre-cryopreserved, nucleated cell dose of at least 2.5 x 10\^7 per kilogram and the second unit delivers at least 1.5 x 10\^7 per kilogram. Patients will be randomized no more than 14 days prior to initiation of conditioning. UCB units will be shipped prior to initiation of conditioning. The preparative regimen will consist of the following: * Fludarabine: 25 mg/m2/day IV on Days -10, -9, and -8. * Total Body Irradiation (TBI): 165 cGy twice daily on Days -7, -6, -5, and -4. * Cyclophosphamide: 60 mg/kg/day x 2 on Days -3 and -2. * Day 0 will be the day of the UCB transplant. The Graft-vs-Host-Disease (GVHD) prophylaxis regimen will be mycophenolate mofetil (MMF) 15 mg/kg IV BID on Day -3 to Day + 45 and cyclosporine A (CSA) to maintain level 200-400 ng/mL beginning on Day -3. Patients will be followed for at least 24 months post-transplant.
Interventions
BIOLOGICALSingle Umbilical Cord Blood Unit Transplant
Unrelated donor, single umbilical cord blood unit; conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF
BIOLOGICALDouble Umbilical Cord Blood Unit Transplant
Unrelated donor, double umbilical cord blood unit; Conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF
RADIATIONTotal Body Irradiation
The TBI will be delivered from either a linear accelerator or cobalt source at a dose rate of between 4 and 26 cGy/minute using energies of between 1 and 25 MV.
DRUGCyclophosphamide
Cyclophosphamide 60 mg/kg/day will be administered as a 2 hour intravenous infusion with a high volume fluid flush on Days -3 and -2.
DRUGFludarabine
Fludarabine 25 mg/m2/day will be administered over 30-60 minutes intravenous infusion on Days -10 through -8. Fludarabine will not be dose adjusted for body weight.
DRUGCyclosporine A
CSA will be administered beginning on Day -3 and doses will be adjusted to maintain a level of 200-400 ng/mL by TDX method (or 100-250 ng/mL by Tandem MS or equivalent level for other CSA testing methods). CSA can be administered per institutional practice.
DRUGMycophenolate Mofetil
MMF will be given at a dose of 1 gram IV q 8 hours if \> 50 kg or 15 mg/kg IV q 8 hours if \< 50 kg beginning the morning of Day -3.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Blood and Marrow Transplant Clinical Trials Network
National Cancer Institute (NCI)
National Marrow Donor Program
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
* Two partially HLA-matched UCB units. Units must be HLA-matched minimally at 4 of 6 HLA-A and B (at intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular typing) loci with the patient, and the units must be HLA-matched at 3 of 6 HLA- A, B, DRB1 loci with each other (using same resolution of molecular typing as indicated above). Two appropriately HLA-matched units must be available such that one unit delivers a pre-cryopreserved nucleated cell dose of at least 2.5 x 10\^7 per kilogram and the second unit at least 1.5 x 10\^7 per kilogram. * Acute myelogenous leukemia (AML) at the following stages: 1. High risk first complete remission (CR1), defined as the following: * Having preceding myelodysplasia (MDS) * High risk cytogenetics (high risk cytogenetics: del (5q) -5, -7, abn (3q), t (6;9) complex karyotype \[at least 5 abnormalities\],)the presence of a high FLT3 ITD-AR (\> 0.4) * Requiring more than 1 cycle of chemotherapy to obtain complete remission (CR); * FAB M6 2. Second or greater CR 3. First relapse with less than 25% blasts in bone marrow 4. Morphologic complete remission with incomplete blood count recovery * Therapy-related AML for which prior malignancy has been in remission for at least 12 months * Acute lymphocytic leukemia (ALL) at the following stages: 1. High risk first remission, defined as one of the following conditions: * Philadelphia chromosome-positive adult lymphoblastic leukemia (Ph+ ALL) * Mixed lineage leukemia (MLL) rearrangement with slow early response (defined as having M2 \[5-25% blasts\] or M3 \[more than 25% blasts on bone marrow examination on Day 14 of induction therapy\]) * Hypodiploidy (less than 44 chromosomes or DNA index less than 0.81) * End of induction M3 bone marrow * End of induction M2 with M2-3 at Day 42 * Evidence of minimal residual disease (MRD). If a patient's only high risk criterion is MRD, approval by a protocol chair or protocol officer is required for enrollment. For COG centers, this will only be for MRD greater than 1 percent by flow MRD at the end of extended induction. 2. High risk second remission, defined as one of the following conditions: * Philadelphia chromosome-positive adult lymphoblastic leukemia (Ph+ ALL) * Bone marrow relapse less than 36 months from induction * T-lineage relapse at any time * Very early isolated central nervous system (CNS) relapse (6 months from diagnosis) * Slow reinduction (M2-3 at Day 28) after relapse at any time * Evidence of minimal residual disease (MRD). If a patient's only high risk criterion is MRD, approval by a protocol chair or protocol officer is required for enrollment. For COG centers, this will only be for MRD greater than 1 percent by flow MRD at the end of extended induction. 3. Any third or subsequent CR * NK cell lymphoblastic leukemia in any CR * Biphenotypic or undifferentiated leukemia in any CR or if in first relapse must have less than 25% blasts in bone marrow (BM) * Myelodysplastic syndrome (MDS) at any stage * Chronic myelogenous leukemia (CML) in chronic or accelerated phase * All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study. * Patients 16 years old or older must have a Karnofsky score of at least 70% and patients younger than 16 years old must have a Lansky score of at least 70%. * Patients with adequate physical function as measured by: 1. Cardiac: Left ventricular ejection fraction greater than 40% or shortening fraction greater than 26% 2. Hepatic: Bilirubin no more than 2.5 mg/dL; alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) no more than 5 times the upper limit of normal (ULN) 3. Renal: Serum creatinine within normal range for age, or if serum creatinine is outside normal range for age, then renal function (creatinine clearance or GFR) greater than 70 mL/min/1.73 m\^2 4. Pulmonary: Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), or forced vital capacity (FVC) greater than 50% of predicted value (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation greater than 92% of room air
Exclusion criteria
* Pregnant (β-positive human chorionic gonadotropin \[HCG\]) or breastfeeding * Evidence of HIV infection or HIV positive serology * Current uncontrolled bacterial, viral, or fungal infection (currently taking medication and progression of clinical symptoms) * Autologous transplant less than 12 months prior to enrollment * Prior autologous transplant for the disease for which the UCB transplant will be performed * Prior allogeneic hematopoietic stem cell transplant * Active malignancy other than the one for which the UCB transplant is being performed within 12 months of enrollment * Inability to receive TBI * Requirement of supplemental oxygen * HLA-matched related donor able to donate
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Overall Survival | 1 year post-randomization | Overall survival is defined as survival of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Neutrophil and Platelet Engraftment | Days 42 and 100 | Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10\^6/liter for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 50,000/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 to Neutrophil and Platelet Engraftment | 2 years post-transplant | Platelet engraftment is defined as achieving platelet counts greater than 50,000/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. |
| Percentage of Participants With Acute Graft-versus-host Disease (GVHD) | Day 100 post-randomization | Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. 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 |
| Percentage of Participants With Chronic GVHD | 1 year post-randomization | Incidences of chronic GVHD will be graded per Shulman et al. 1980. This reference categorizes chronic GVHD as either limited or extensive. For this outcome, participants developing either type are considered to have a chronic GVHD event. |
| Percentage of Participants With Disease-free Survival | 1 year post-randomization | Disease-free survival is defined as survival without relapse of the primary disease. |
| Percentage of Participants With Relapse | 1 year post-randomization | Relapse is defined by either morphological or cytogenetic evidence of AML, ALL, CML, or MDS consistent with pre-transplant features. Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation. |
| Percentage of Participants With Treatment-related Mortality | 1 year post-randomization | Treatment related mortality is defined as death without relapse of the primary disease. |
| Number of Participants With Engraftment Syndrome | Day 100 post-transplant | — |
| Number of Infections Per Participant | 2 years post-randomization | — |
Countries
Australia, Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single UCB Transplant Single Umbilical Cord Blood Unit Transplantation | 113 |
| Double UCB Transplant Double Umbilical Cord Blood Unit Transplantation | 111 |
| Total | 224 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Not Transplanted | 1 | 2 |
Baseline characteristics
| Characteristic | Single UCB Transplant | Total | Double UCB Transplant |
|---|---|---|---|
| Acute Biphenotypic Leukemia Disease Status First Complete Remission (CR) | 5 Participants | 6 Participants | 1 Participants |
| Acute Biphenotypic Leukemia Disease Status Second CR | 1 Participants | 2 Participants | 1 Participants |
| Age, Continuous | 10.4 years STANDARD_DEVIATION 5.1 | 10.4 years STANDARD_DEVIATION 5.1 | 10.4 years STANDARD_DEVIATION 5.1 |
| ALL Disease Status First Complete Remission (CR) | 19 Participants | 38 Participants | 19 Participants |
| ALL Disease Status Morphologic CR before Complete-Blood-Count Recover | 0 Participants | 1 Participants | 1 Participants |
| ALL Disease Status Second CR | 29 Participants | 57 Participants | 28 Participants |
| ALL Disease Status Subsequent CR | 13 Participants | 23 Participants | 10 Participants |
| AML Disease Status First Complete Remission (CR) | 17 Participants | 31 Participants | 14 Participants |
| AML Disease Status First Relapse | 1 Participants | 4 Participants | 3 Participants |
| AML Disease Status Morphologic CR before Complete-Blood-Count Recover | 2 Participants | 4 Participants | 2 Participants |
| AML Disease Status Secondary or Therapy-related | 3 Participants | 3 Participants | 0 Participants |
| AML Disease Status Second or Later CR | 16 Participants | 35 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 22 Participants | 42 Participants | 20 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 88 Participants | 176 Participants | 88 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 6 Participants | 3 Participants |
| Karnofsky Performance Score 100% | 58 Participants | 115 Participants | 57 Participants |
| Karnofsky Performance Score 70% | 4 Participants | 6 Participants | 2 Participants |
| Karnofsky Performance Score 80% | 13 Participants | 22 Participants | 9 Participants |
| Karnofsky Performance Score 90% | 38 Participants | 81 Participants | 43 Participants |
| MDS Disease Status Refractory Anemia | 2 Participants | 2 Participants | 0 Participants |
| MDS Disease Status Refractory Anemia with Excess Blasts 1 (RAEB1) | 0 Participants | 3 Participants | 3 Participants |
| MDS Disease Status Refractory Anemia with Excess Blasts 2 (RAEB2) | 0 Participants | 4 Participants | 4 Participants |
| MDS Disease Status Refractory Cytopenia with Multilineage Dysplasia | 2 Participants | 5 Participants | 3 Participants |
| MDS Disease Status Unclassified | 1 Participants | 4 Participants | 3 Participants |
| Primary Disease Acute Biphenotypic Leukemia | 6 Participants | 8 Participants | 2 Participants |
| Primary Disease Acute Lymphoblastic Leukemia (ALL) | 61 Participants | 119 Participants | 58 Participants |
| Primary Disease Acute Myelogenous Leukemia (AML) | 39 Participants | 77 Participants | 38 Participants |
| Primary Disease Acute Undifferentiated Leukemia | 1 Participants | 1 Participants | 0 Participants |
| Primary Disease Chronic Myelogenous Leukemia (CML) | 1 Participants | 1 Participants | 0 Participants |
| Primary Disease Myelodysplastic Syndrome (MDS) | 5 Participants | 18 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 9 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 24 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 12 Participants | 19 Participants | 7 Participants |
| Race (NIH/OMB) White | 80 Participants | 165 Participants | 85 Participants |
| Recipient CMV Status Inconclusive | 1 Participants | 2 Participants | 1 Participants |
| Recipient CMV Status Negative | 51 Participants | 90 Participants | 39 Participants |
| Recipient CMV Status Positive | 58 Participants | 124 Participants | 66 Participants |
| Recipient CMV Status Unknown | 3 Participants | 8 Participants | 5 Participants |
| Recipient to First Cord Blood Unit ABO Match Bidirectional Mismatch | 10 Participants | 18 Participants | 8 Participants |
| Recipient to First Cord Blood Unit ABO Match Major Mismatch | 30 Participants | 55 Participants | 25 Participants |
| Recipient to First Cord Blood Unit ABO Match Minor Mismatch | 24 Participants | 59 Participants | 35 Participants |
| Recipient to First Cord Blood Unit ABO Match No Mismatch | 44 Participants | 80 Participants | 36 Participants |
| Recipient to First Cord Blood Unit ABO Match Unknown | 4 Participants | 8 Participants | 4 Participants |
| Recipient to First Cord Blood Unit HLA Match 3/6 | 1 Participants | 3 Participants | 2 Participants |
| Recipient to First Cord Blood Unit HLA Match 4/6 | 44 Participants | 77 Participants | 33 Participants |
| Recipient to First Cord Blood Unit HLA Match 5/6 | 51 Participants | 110 Participants | 59 Participants |
| Recipient to First Cord Blood Unit HLA Match 6/6 | 16 Participants | 30 Participants | 14 Participants |
| Recipient to Second Cord Blood Unit ABO Match Bidirectional mismatch | — | 4 Participants | 4 Participants |
| Recipient to Second Cord Blood Unit ABO Match Major mismatch | — | 31 Participants | 31 Participants |
| Recipient to Second Cord Blood Unit ABO Match Minor mismatch | — | 29 Participants | 29 Participants |
| Recipient to Second Cord Blood Unit ABO Match No mismatch | — | 38 Participants | 38 Participants |
| Recipient to Second Cord Blood Unit ABO Match Unknown | — | 6 Participants | 6 Participants |
| Recipient to Second Cord Blood Unit HLA Match 3/6 | — | 1 Participants | 1 Participants |
| Recipient to Second Cord Blood Unit HLA Match 4/6 | — | 43 Participants | 43 Participants |
| Recipient to Second Cord Blood Unit HLA Match 5/6 | — | 43 Participants | 43 Participants |
| Recipient to Second Cord Blood Unit HLA Match 6/6 | — | 21 Participants | 21 Participants |
| Sex: Female, Male Female | 55 Participants | 96 Participants | 41 Participants |
| Sex: Female, Male Male | 58 Participants | 128 Participants | 70 Participants |
| Weight at Infusion | 39.6 kilograms STANDARD_DEVIATION 20.2 | 39.15 kilograms STANDARD_DEVIATION 19.7 | 38.7 kilograms STANDARD_DEVIATION 19.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 112 | 0 / 108 |
| serious Total, serious adverse events | 5 / 112 | 14 / 108 |
Outcome results
Primary
Percentage of Participants With Overall Survival
Overall survival is defined as survival of death from any cause.
Time frame: 1 year post-randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single UCB Transplant | Percentage of Participants With Overall Survival | 73 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Overall Survival | 65 percentage of participants |
Comparison: The null hypothesis is that there is no difference in overall survival at one year post-randomization between participants receiving single- and double-unit cord blood transplant. The targeted sample size of 110 participants per treatment group was sufficient to maintain a type I error rate of 5% and provide more than 86% power to detect an increase in overall survival from 57% among participants receiving a single unit graft to 77% for those receiving a double-unit graft.p-value: 0.17Log Rank
Secondary
Number of Infections Per Participant
Time frame: 2 years post-randomization
Population: Transplanted participants
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Single UCB Transplant | Number of Infections Per Participant | 0 | 10 Participants |
| Single UCB Transplant | Number of Infections Per Participant | 1 | 15 Participants |
| Single UCB Transplant | Number of Infections Per Participant | 2 | 12 Participants |
| Single UCB Transplant | Number of Infections Per Participant | 3 | 19 Participants |
| Single UCB Transplant | Number of Infections Per Participant | 4 | 17 Participants |
| Single UCB Transplant | Number of Infections Per Participant | 5 | 7 Participants |
| Single UCB Transplant | Number of Infections Per Participant | 6-10 | 19 Participants |
| Single UCB Transplant | Number of Infections Per Participant | More than 10 | 13 Participants |
| Double UCB Transplant | Number of Infections Per Participant | More than 10 | 10 Participants |
| Double UCB Transplant | Number of Infections Per Participant | 0 | 9 Participants |
| Double UCB Transplant | Number of Infections Per Participant | 4 | 15 Participants |
| Double UCB Transplant | Number of Infections Per Participant | 1 | 13 Participants |
| Double UCB Transplant | Number of Infections Per Participant | 6-10 | 24 Participants |
| Double UCB Transplant | Number of Infections Per Participant | 2 | 15 Participants |
| Double UCB Transplant | Number of Infections Per Participant | 5 | 12 Participants |
| Double UCB Transplant | Number of Infections Per Participant | 3 | 10 Participants |
Secondary
Number of Participants With Engraftment Syndrome
Time frame: Day 100 post-transplant
Population: Transplanted participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single UCB Transplant | Number of Participants With Engraftment Syndrome | 11 Participants |
| Double UCB Transplant | Number of Participants With Engraftment Syndrome | 7 Participants |
Secondary
Percentage of Participants With Acute Graft-versus-host Disease (GVHD)
Acute GVHD is graded according to the scoring system proposed by Przepiorka et al.1995: Skin stage: 0: No rash 1. Rash \<25% of body surface area 2. Rash on 25-50% of body surface area 3. Rash on \> 50% of body surface area 4. Generalized erythroderma with bullous formation Liver stage (based on bilirubin level)\*: 0: \<2 mg/dL 1. 2-3 mg/dL 2. 3.01-6 mg/dL 3. 6.01-15.0 mg/dL 4. \>15 mg/dL GI stage\*: 0: No diarrhea or diarrhea \<500 mL/day 1. Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD 2. Diarrhea 1000-1499 mL/day 3. Diarrhea \>1500 mL/day 4. 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-randomization
Population: Transplanted participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single UCB Transplant | Percentage of Participants With Acute Graft-versus-host Disease (GVHD) | Acute GVHD Grade II-IV | 57 percentage of participants |
| Single UCB Transplant | Percentage of Participants With Acute Graft-versus-host Disease (GVHD) | Acute GVHD Grade III-IV | 13 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Acute Graft-versus-host Disease (GVHD) | Acute GVHD Grade II-IV | 56 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Acute Graft-versus-host Disease (GVHD) | Acute GVHD Grade III-IV | 23 percentage of participants |
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of Grade II-IV acute GVHD between participants receiving single- and double-unit cord blood transplant.p-value: 0.78Gray's test
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of Grade III-IV acute GVHD between participants receiving single- and double-unit cord blood transplant.p-value: 0.02Gray's test
Secondary
Percentage of Participants With Chronic GVHD
Incidences of chronic GVHD will be graded per Shulman et al. 1980. This reference categorizes chronic GVHD as either limited or extensive. For this outcome, participants developing either type are considered to have a chronic GVHD event.
Time frame: 1 year post-randomization
Population: Transplanted participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single UCB Transplant | Percentage of Participants With Chronic GVHD | Chronic GVHD | 30 percentage of participants |
| Single UCB Transplant | Percentage of Participants With Chronic GVHD | Extensive Chronic GVHD | 9 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Chronic GVHD | Chronic GVHD | 32 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Chronic GVHD | Extensive Chronic GVHD | 15 percentage of participants |
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of chronic GVHD between participants receiving single- and double-unit cord blood transplant.p-value: 0.51Gray's test
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of extensive chronic GVHD between participants receiving single- and double-unit cord blood transplant.p-value: 0.05Gray's test
Secondary
Percentage of Participants With Disease-free Survival
Disease-free survival is defined as survival without relapse of the primary disease.
Time frame: 1 year post-randomization
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single UCB Transplant | Percentage of Participants With Disease-free Survival | 70 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Disease-free Survival | 64 percentage of participants |
Comparison: The null hypothesis is that there is no difference in disease-free survival at one year post-randomization between participants receiving single- and double-unit cord blood transplant.p-value: 0.11Log Rank
Secondary
Percentage of Participants With Neutrophil and Platelet Engraftment
Neutrophil engraftment is defined as achieving an absolute neutrophil count greater than 500x10\^6/liter for three consecutive measurements on different days. The first of the three days will be designated the day of neutrophil engraftment. Platelet engraftment is defined as achieving platelet counts greater than 50,000/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 42 and 100
Population: Transplanted participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Single UCB Transplant | Percentage of Participants With Neutrophil and Platelet Engraftment | Platelet Engraftment at Day 100 | 76 percentage of participants |
| Single UCB Transplant | Percentage of Participants With Neutrophil and Platelet Engraftment | Neutrophil Engraftment at Day 42 | 89 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Neutrophil and Platelet Engraftment | Neutrophil Engraftment at Day 42 | 88 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Neutrophil and Platelet Engraftment | Platelet Engraftment at Day 100 | 65 percentage of participants |
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of neutrophil engraftment between participants receiving single- and double-unit cord blood transplant.p-value: 0.29Gray's test
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of platelet engraftment between participants receiving single- and double-unit cord blood transplant.p-value: 0.04Gray's test
Secondary
Percentage of Participants With Relapse
Relapse is defined by either morphological or cytogenetic evidence of AML, ALL, CML, or MDS consistent with pre-transplant features. Testing for recurrent malignancy in the blood, marrow or other sites will be used to assess relapse after transplantation.
Time frame: 1 year post-randomization
Population: Transplanted participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single UCB Transplant | Percentage of Participants With Relapse | 12 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Relapse | 14 percentage of participants |
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of relapse between participants receiving single- and double-unit cord blood transplant.p-value: 0.12Gray's test
Secondary
Percentage of Participants With Treatment-related Mortality
Treatment related mortality is defined as death without relapse of the primary disease.
Time frame: 1 year post-randomization
Population: Transplanted participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Single UCB Transplant | Percentage of Participants With Treatment-related Mortality | 19 percentage of participants |
| Double UCB Transplant | Percentage of Participants With Treatment-related Mortality | 22 percentage of participants |
Comparison: The null hypothesis is that there is no difference in the cumulative incidence of treatment-related mortality between participants receiving single- and double-unit cord blood transplant.p-value: 0.43Gray's test
Secondary
Time to Neutrophil and Platelet Engraftment
Platelet engraftment is defined as achieving platelet counts greater than 50,000/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: 2 years post-transplant
Population: Transplanted participants
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Single UCB Transplant | Time to Neutrophil and Platelet Engraftment | Neutrophil Engraftment | 21 days |
| Single UCB Transplant | Time to Neutrophil and Platelet Engraftment | Platelet Engraftment | 58 days |
| Double UCB Transplant | Time to Neutrophil and Platelet Engraftment | Neutrophil Engraftment | 23 days |
| Double UCB Transplant | Time to Neutrophil and Platelet Engraftment | Platelet Engraftment | 84 days |