UCAML: Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies

• Sponsor: Baylor College of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01247701
• Collaborator: Center for Cell and Gene Therapy, Baylor College of Medicine (Other)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 107
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

In this study, the investigators will use busulfan and cyclophosphamide (BuCy) backbone with the addition of fludarabine as the preparative Stem Cell Transplant (SCT) regimen. As an attempt to improve engraftment rate and reduce infections, the investigators are going to incorporate fludarabine in the conditioning regimen. The use of a BuCy backbone has been widely used and comparable to total body irradiation and cyclophosphamide (Cy/TBI) regimen.

Encouraging data on adding fludarabine to the SCT regimen have been reported. A fludarabine-based, conditioning regimen, with adequate immunosuppressive activity could conceivably allow engraftment of stem cells from alternative donors in hematologic malignancies patients with acceptable engraftment rates and low transplant-related mortality. Regimen-related toxicity is believed to be a major contributing factor to GVHD. Therefore this approach may also lead to reduced GVHD, as some investigators have suggested.

In an attempt to decrease the rate of viral infection and reactivation, the investigators will avoid ATG (Thymoglobulin) / Campath (anti-CD52), and instead administer Mycophenolate Mofetil (MMF). The addition of fludarabine should compensate any increase risk of graft failure with the removal of the ATG/Campath. The investigators anticipate that the removal of ATG/Campath will facilitate immune reconstitution more efficiently after receiving a UCBT.

Condition or Disease	Intervention/Treatment	Phase
Myeloid Hematological Malignancies	Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Cord Blood Stem Cell Infusion	N/A

Detailed Description

The following will be given as the conditioning regimen for the transplant:

BUSULFAN: Busulfan (intravenous BUSULFEX) dosing will be as follows: patients <12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. Administration and pharmacokinetic monitoring will be performed as per standard practice. Anticonvulsants will be given in accordance with standard Blood and Marrow Transplant Program recommendations.

CYCLOPHOSPHAMIDE: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Mesna will be given in accordance with standard Blood and Marrow Transplant.

FLUDARABINE: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m2. Preparation, administration and monitoring will be according to standard practice procedure

POST-TRANSPLANT IMMUNOSUPPRESSION:

• CSA will begin on Day -3. For children < 40 kg, the initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. Dose adjustments will be made to maintain levels above 200 ng/mL. Levels will be done on Day 0 and then as clinical indicated. CSA will be tapered per institutional SOP. Once the patient can tolerate oral medications and has a normal gastrointestinal transit time, CSA will be converted to an oral form.

• MMF will begin on Day 0 at a dose of 15 mg/Kg IV or orally TID, and will be discontinued on Day +45 unless GVHD is present.

CNS Disease: Patients with CNS relapse or primary CNS disease that is symptomatic or associated to radiological changes will receive additional irradiation to the craniospinal axis.

SUPPORTIVE CARE:

• Supportive care will be provided as per standard practice of the Blood and Marrow Stem Cell Transplant program at the Texas Children's Hospital, including all prophylactic and therapeutic clinical care issues. These practices may be modified if necessary for any individual patient in order to provide optimum care for that particular patient.

• IVIG: Intravenous immunoglobulin (500 mg/kg per dose) will be given monthly until discontinuation of GVHD therapy and documentation of antibody production.

• CB-CTLs: Patients enrolled in this protocol may also be eligible for infusion of CB-derived multivirus-specific CTL to provide virus-specific immune reconstitution and treatment of viral infections after CBT.

EVALUATIONS DURING THE STUDY:

Screening Procedures; Pre-HCT:

• Physical examination

• Pregnancy test

• Complete blood count and chemistries

• Electrocardiogram

• Echocardiograph

• PT/PTT/Fibrinogen/Anti-Thrombin III/von Willebrand Factor

• Viral tests

• Bone marrow aspirate and biopsy/Lumbar puncture

• Renal Function (GFR)

• Lumbar puncture will be performed

• Pulmonary Function test

EVALUATIONS BETWEEN DAY 0 AND DAY 100:

• Physical examination

• Complete blood count and chemistries

• Lytes/BUN/Cr

• Peripheral blood for STRs or FISH analysis for molecular diagnostics

• Lymphocyte phenotype testing and lymphoproliferative responses

• Bone marrow aspirate and biopsy for assessment of leukemia status and UCB engraftment

• Lumbar puncture

• Immunoglobulins

EVALUATIONS AFTER DAY 100:

• Physical examination

• Complete blood count and chemistries

• Lytes/BUN/Cr

• Serum chemistries

• Peripheral blood with assessment of engraftment by STRs or FISH analysis and enzyme levels

• Echocardiograph with LVEF

• Bone marrow aspirate and biopsy assessment of leukemia status and UCB engraftment

• Lymphocyte phenotype testing (CD3, CD4, CD8, CD19 and CD56) and lymphoproliferative responses

• Immunoglobulins

FOLLOW-UP INTERVAL:

Patients will be seen in the hospital everyday until discharge. After discharge from the hospital, the patient will be following on the BMT clinics on a regular basis as recommended by the primary physician.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies (UCAML)
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: Oct 1, 2019
• Actual Study Completion Date: Oct 1, 2019

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Umbilical Cord Blood Transplant Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion

Drug: Busulfan; Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6.; Other Names: Busulfex ; Drug: Cyclophosphamide; Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg.; Other Names: CTX, Cytoxan ; Drug: Fludarabine; Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2.; Other Names: Fludera ; Procedure: Cord Blood Stem Cell Infusion; The cord blood stem cells will be infused on Day 0.

Outcome Measures

Primary Outcome Measures

1. Overall Survival at 100 Days, 1 Year, and 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients. [100 days, 1 year, and 3 years]

   To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.

Secondary Outcome Measures

1. Number of Participants With Severe Acute GVHD Grade III-IV [Day 100]

   Number of participants with acute GVHD graded by the method of Przepiorka et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD.

2. Number of Participants With Chronic GvHD [1 year]

   Number of participants with chronic GVHD graded by the method of Przepiorka et al, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3.

3. Number of Participants With Relapse Rate After Transplant [1 and 3 years]

   To assess relapse rate at 1 and 3 years after transplant. Cumulative incidence of relapse was calculated from the date of umbilical cord blood transplant using the competing risk method as described in Gray(1988) with death prior to relapse as the competing risk. Participants still alive without a date of relapse were censored at the time of the last follow-up.

4. Number of Participants With Donor Engraftment After Transplant. [100 days, 6, 9, 12, 24 and 36 months]

   To evaluate donor engraftment at 100 days, 6, 9, 12, 24, and 36 months after transplant.

5. Number of Participants With Platelet Engraftment [Day 180]

   Achievement of untransfused platelet count > 20 x 10^9/L on three consecutive days

6. Number of Participants With Neutrophil Engraftment [Day 42]

   Achievement of absolute neutrophil count > 0.5 x 10^9/L on three consecutive days

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients with a myeloid hematologic malignancy (acute myelogenous leukemia, secondary myelogenous leukemia or myelodysplastic syndrome) unlikely to be cure by standard chemotherapy. This includes patients who have relapsed after standard chemotherapy treatments and patients in first remission with unfavorable prognostics features.

• Related or Unrelated Umbilical Cord Blood Unit with 0-1 antigen mismatch at HLA-A and B (at low resolution) and DRB1 (at high resolution), with a total nucleated cell dose of ≥ 4 x 10^7/kg.

• Lansky/Karnofsky scores at least 60.

• Written informed consent and/or signed assent line from patient, parent or guardian.

• Negative pregnancy test, if applicable.

Exclusion Criteria:

• Patients with uncontrolled infections. For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection for 72 hours prior to enrollment. For fungal infections, patients must be receiving definitive systemic antifungal therapy and have no signs of progressing infection for 1 week prior to enrollment. Progressing infection is defined as hemodynamic instability attributable to sepsis or new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.

• Severe renal disease (Creatinine > 3X normal for age).

• Severe hepatic disease (direct bilirubin > 3 mg/dL or SGOT > 500).

• Patient has DLCO < 50% predicted or FEV1 < 50% of predicted, if applicable.

• Patients with symptomatic cardiac failure unrelieved by medical therapy or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction < 20%).

• HIV positive.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Texas Children's Hospital	Houston	Texas	United States	77030

Sponsors and Collaborators

• Baylor College of Medicine
• Center for Cell and Gene Therapy, Baylor College of Medicine

Investigators

• Principal Investigator: Caridad A Martinez, MD, Baylor College of Medicine
• Principal Investigator: Robert A Krance, MD, Baylor College of Medicine

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jun 29, 2021
• Informed Consent Form - Aug 17, 2018

More Information

Publications

None provided.

• Responsible Party: Caridad Martinez, Assistant Professor, Pediatric Hematology/Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT01247701
• Other Study ID Numbers: 26558-UCAML
• First Posted: Nov 24, 2010
• Last Update Posted: Jun 8, 2022
• Last Verified: May 1, 2022

• Keywords provided by Caridad Martinez, Assistant Professor, Pediatric Hematology/Oncology, Center for Cell and Gene Therapy, Baylor College of Medicine: UCB; Umbilical Cord Blood; Transplant; Umbilical Cord Blood Transplant; Cord Blood Stem Cell Transplantation; Pediatric; Myeloid Hematological Malignancies; Busulfan; Cytoxan; Cyclophosphamide; Fludarabine
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Cyclophosphamide; Busulfan; Fludarabine

Study Results

Participant Flow

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Period Title: Overall Study
STARTED	16
COMPLETED	6
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Overall Participants	16
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	1.5
Sex: Female, Male (Count of Participants)
Female	5 31.3%
Male	11 68.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 56.3%
Not Hispanic or Latino	7 43.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 6.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 18.8%
White	12 75%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival at 100 Days, 1 Year, and 3 Years After Umbilical Cord Blood Transplant in Pediatric Patients.
Description	To determine the overall survival rate at 1 year after umbilical cord blood transplant in pediatric patients with myeloid hematological malignancies.
Time Frame	100 days, 1 year, and 3 years

Outcome Measure Data

Analysis Population Description

The analysis included all participants who enrolled in the study and underwent umbilical cord blood transplant (UCBT) except the one participant who died 4 days after transplant.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Measure Participants	15
100 days	0.923
1-Year	0.923
3-Year	0.923

2. Secondary Outcome

Title	Number of Participants With Severe Acute GVHD Grade III-IV
Description	Number of participants with acute GVHD graded by the method of Przepiorka et al, which evaluates skin involvement, lower and upper GI, and liver function (bilirubin), each being graded in stages from 0 to 4, where 0 means no acute GVHD, and 4 is the highest stage of acute GVHD.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

The analysis included all participants who underwent Umbilical Cord Blood Transplant (UCBT) and were evaluable for acute GVHD. A participant was evaluable for acute GVHD if he/she engrafted and either completed 100 days observation after transplant or experienced acute GVHD.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Measure Participants	15
Count of Participants [Participants]	2 12.5%

3. Secondary Outcome

Title	Number of Participants With Chronic GvHD
Description	Number of participants with chronic GVHD graded by the method of Przepiorka et al, which evaluates skin, joints, oral, ocular, hepatic, esophagus, GI, respiratory, platelet, and musculoskeletal involvement, in stages from 0 to 3.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The analysis included all enrolled participants who underwent umbilical cord blood transplant (UCBT) and were evaluable for chronic GVHD. A participant was evaluable for chronic GVHD if he/she engrafted and survived or remained in the study for more than 100 days after transplant. However, if the participant(s) relapsed within or around 100 days, they would not be evaluable.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Measure Participants	10
Count of Participants [Participants]	1 6.3%

4. Secondary Outcome

Title	Number of Participants With Relapse Rate After Transplant
Description	To assess relapse rate at 1 and 3 years after transplant. Cumulative incidence of relapse was calculated from the date of umbilical cord blood transplant using the competing risk method as described in Gray(1988) with death prior to relapse as the competing risk. Participants still alive without a date of relapse were censored at the time of the last follow-up.
Time Frame	1 and 3 years

Outcome Measure Data

Analysis Population Description

The analysis included all participants who enrolled in the study and underwent umbilical cord blood transplant (UCBT) except the one participant who died 4 days after transplant.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Measure Participants	15
1 year	53.3 333.1%
3 year	53.3 333.1%

5. Secondary Outcome

Title	Number of Participants With Donor Engraftment After Transplant.
Description	To evaluate donor engraftment at 100 days, 6, 9, 12, 24, and 36 months after transplant.
Time Frame	100 days, 6, 9, 12, 24 and 36 months

Outcome Measure Data

Analysis Population Description

The analysis included all participants who underwent umbilical cord blood transplant (UCBT) except the one participant who died 4 days after transplant. If the participant(s) relapsed, they would not be evaluable for donor engraftment.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Measure Participants	12
100 days	11 68.8%
6 months	6 37.5%
9 months	6 37.5%
12 months	6 37.5%
24 months	6 37.5%
36 months	3 18.8%

6. Secondary Outcome

Title	Number of Participants With Platelet Engraftment
Description	Achievement of untransfused platelet count > 20 x 10^9/L on three consecutive days
Time Frame	Day 180

Outcome Measure Data

Analysis Population Description

The analysis included all participants who enrolled in the study and underwent umbilical cord blood transplant (UCBT) except the one participant who died 4 days after transplant.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Measure Participants	15
Count of Participants [Participants]	13 81.3%

7. Secondary Outcome

Title	Number of Participants With Neutrophil Engraftment
Description	Achievement of absolute neutrophil count > 0.5 x 10^9/L on three consecutive days
Time Frame	Day 42

Outcome Measure Data

Analysis Population Description

The analysis included all participants who enrolled in the study and underwent umbilical cord blood transplant (UCBT) except the one participant who died 4 days after transplant.

Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
Measure Participants	15
Count of Participants [Participants]	15 93.8%

Adverse Events

Time Frame	We have recorded all grade 3 and 4 toxicities, except hematological toxicities, fever, abnormal glucose, ALT, GGT, and K levels from the day conditioning started until day 30 post-transplant. SAEs were reported up to day 100. Our study primary outcome is Overall Survival (OS) up to 3 years after transplant. The use of AEs up to 100 days is the standard measurement after a stem cell transplant. OS will capture any major toxicity up to 3 years after transplant that will lead to mortality.
Adverse Event Reporting Description	The analysis included all participants who enrolled in the study and underwent umbilical cord blood transplant (UCBT).
Arm/Group Title	Umbilical Cord Blood Transplant
Arm/Group Description	Busulfan,Cyclophosphamide, Fludarabine, Cord Blood Stem Cell Infusion Busulfan: Busulfan dosing will be as follows: Patients < 12 kg: 1.1 mg/kg/dose IV every 6 hours for 16 doses total; patients > 12 kg: 0.8 mg/kg/dose IV every 6 hours for 16 doses. It will be given on Days -9, -8, -7 and -6. Cyclophosphamide: Cyclophosphamide (50 mg/kg/dose) will be given IV on Days -5, - 4, -3, and -2 over 1 hour. The total dose to be given over 4 days is 200 mg/kg. Fludarabine: Fludarabine will be given IV daily over 1 hour for 3 days. Dosing will be as follows: for patients ≤ 10 kg: 1.3 mg/kg; for patients > 10 kg: 40 mg/m^2. Cord Blood Stem Cell Infusion: The cord blood stem cells will be infused on Day 0.
All Cause Mortality
	Umbilical Cord Blood Transplant
	Affected / at Risk (%)	# Events
Total	2/16 (12.5%)
Serious Adverse Events
	Umbilical Cord Blood Transplant
	Affected / at Risk (%)	# Events
Total	11/16 (68.8%)
Cardiac disorders
Cardiac arrest	1/16 (6.3%)	1
Gastrointestinal disorders
Intra-abdominal hemorrhage	1/16 (6.3%)	1
Hepatobiliary disorders
Hepatobiliary disorders - Other, specify: VOD	1/16 (6.3%)	1
Infections and infestations
Catheter related infection	4/16 (25%)	5
Endocarditis infective	1/16 (6.3%)	1
Infections and infestations - Other, specify: Adenovirus in plasma and adenovirus enteritis	1/16 (6.3%)	1
Infections and infestations - Other, specify: BK virus infection with hemorrhagic cystitis	1/16 (6.3%)	1
Infections and infestations - Other, specify: C.Difficile gastroenteritis	1/16 (6.3%)	1
Infections and infestations - Other,specify:Hemorrhagic cystitis due to BK virus uremia and viremia	1/16 (6.3%)	1
Infections and infestations - Other, specify: Sepsis without identified organism	1/16 (6.3%)	1
Lung infection	1/16 (6.3%)	1
Sepsis	2/16 (12.5%)	2
Nervous system disorders
Encephalopathy	1/16 (6.3%)	1
Nervous system disorders - Other, specify: Altered mental status	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	2/16 (12.5%)	2
Respiratory, thoracic and mediastinal disorders - Other, specify: Pulmonary hemorrhage	1/16 (6.3%)	1
Respiratory,thoracic and mediastinal disorders - Other,specify:Respiratory distress after sedation	1/16 (6.3%)	1
Vascular disorders
Vascular disorders - Other, specify: VOD	1/16 (6.3%)	1
Other (Not Including Serious) Adverse Events
	Umbilical Cord Blood Transplant
	Affected / at Risk (%)	# Events
Total	13/16 (81.3%)
Gastrointestinal disorders
Mucositis oral	2/16 (12.5%)	2
Nausea	1/16 (6.3%)	1
Infections and infestations
Catheter related infection	2/16 (12.5%)	2
Infections and infestations - Other, specify: Adenovirus	1/16 (6.3%)	1
Infections and infestations -Other,specify: Hemorrhagic cystitis due to BK virus uremia and viremia	1/16 (6.3%)	1
Infections and infestations - Other, specify: Norovirus viral diarrheal disese	1/16 (6.3%)	1
Infections and infestations - Other, specify: Recurrent Clostridium Difficile colitis	1/16 (6.3%)	1
Investigations
Aspartate aminotransferase increased	1/16 (6.3%)	1
Blood bilirubin increased	2/16 (12.5%)	2
Metabolism and nutrition disorders
Hypermagnesemia	1/16 (6.3%)	1
Hypertriglyceridemia	1/16 (6.3%)	1
Hypocalcemia	2/16 (12.5%)	3
Hyponatremia	1/16 (6.3%)	1
Hypophosphatemia	2/16 (12.5%)	3
Nervous system disorders
Nervous system disorders - Other, specify: Posterior reversible encephalopathy syndrome	1/16 (6.3%)	1
Renal and urinary disorders
Acute kidney injury	1/16 (6.3%)	1
Cystitis noninfective	1/16 (6.3%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify: Respiratory distress	1/16 (6.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.