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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00412360




Registration number
NCT00412360
Ethics application status
Date submitted
14/12/2006
Date registered
18/12/2006
Date last updated
28/10/2021

Titles & IDs
Public title
Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
Scientific title
Multi-center, Open Label, Randomized Trial Comparing Single Versus Double Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia (BMT CTN #0501)
Secondary ID [1] 0 0
2U01HL069294
Secondary ID [2] 0 0
BMTCTN0501
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myelogenous Leukemia 0 0
Acute Lymphocytic Leukemia 0 0
Chronic Myelogenous Leukemia 0 0
Myelodysplastic Syndrome 0 0
Natural Killer Cell Lymphoblastic Leukemia/Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Single Umbilical Cord Blood Unit Transplant
Other interventions - Double Umbilical Cord Blood Unit Transplant
Treatment: Other - Total Body Irradiation
Treatment: Drugs - Cyclophosphamide
Treatment: Drugs - Fludarabine
Treatment: Drugs - Cyclosporine A
Treatment: Drugs - Mycophenolate Mofetil

Experimental: Single Cord Blood Transplant - Unrelated donor, single umbilical cord blood unit transplant; conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil

Experimental: Double Cord Blood Transplant - Unrelated donor, double umbilical cord blood unit transplant; Conditioning regimen: Total Body Irradiation/cyclophosphamide/fludarabine; GVHD prophylaxis: Cyclosporine A/Mycophenolate Mofetil


Other interventions: Single Umbilical Cord Blood Unit Transplant
Unrelated donor, single umbilical cord blood unit; conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF

Other interventions: Double Umbilical Cord Blood Unit Transplant
Unrelated donor, double umbilical cord blood unit; Conditioning regimen: TBI/cyclophosphamide/fludarabine; GVHD prophylaxis: cyclosporine/MMF

Treatment: Other: Total 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.

Treatment: Drugs: Cyclophosphamide
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.

Treatment: Drugs: Fludarabine
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.

Treatment: Drugs: Cyclosporine 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.

Treatment: Drugs: Mycophenolate 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.
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Overall Survival
Timepoint [1] 0 0
1 year post-randomization
Secondary outcome [1] 0 0
Percentage of Participants With Disease-free Survival
Timepoint [1] 0 0
1 year post-randomization
Secondary outcome [2] 0 0
Percentage of Participants With Neutrophil and Platelet Engraftment
Timepoint [2] 0 0
Days 42 and 100
Secondary outcome [3] 0 0
Time to Neutrophil and Platelet Engraftment
Timepoint [3] 0 0
2 years post-transplant
Secondary outcome [4] 0 0
Percentage of Participants With Acute Graft-versus-host Disease (GVHD)
Timepoint [4] 0 0
Day 100 post-randomization
Secondary outcome [5] 0 0
Percentage of Participants With Chronic GVHD
Timepoint [5] 0 0
1 year post-randomization
Secondary outcome [6] 0 0
Number of Infections Per Participant
Timepoint [6] 0 0
2 years post-randomization
Secondary outcome [7] 0 0
Percentage of Participants With Relapse
Timepoint [7] 0 0
1 year post-randomization
Secondary outcome [8] 0 0
Percentage of Participants With Treatment-related Mortality
Timepoint [8] 0 0
1 year post-randomization
Secondary outcome [9] 0 0
Number of Participants With Engraftment Syndrome
Timepoint [9] 0 0
Day 100 post-transplant

Eligibility
Key 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
Minimum age
1 Year
Maximum age
21 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnant (ß-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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/10/2014
Sample size
Target
Accrual to date
Final
224
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Louisiana
Country [11] 0 0
United States of America
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Massachusetts
Country [12] 0 0
United States of America
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Michigan
Country [13] 0 0
United States of America
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Minnesota
Country [14] 0 0
United States of America
State/province [14] 0 0
Mississippi
Country [15] 0 0
United States of America
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Missouri
Country [16] 0 0
United States of America
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New York
Country [17] 0 0
United States of America
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North Carolina
Country [18] 0 0
United States of America
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Ohio
Country [19] 0 0
United States of America
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Oregon
Country [20] 0 0
United States of America
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Pennsylvania
Country [21] 0 0
United States of America
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South Carolina
Country [22] 0 0
United States of America
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Tennessee
Country [23] 0 0
United States of America
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Texas
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United States of America
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Utah
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United States of America
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Virginia
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United States of America
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Washington
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United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia

Funding & Sponsors
Primary sponsor type
Other
Name
Medical College of Wisconsin
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Heart, Lung, and Blood Institute (NHLBI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Blood and Marrow Transplant Clinical Trials Network
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Government body
Name [3] 0 0
National Cancer Institute (NCI)
Address [3] 0 0
Country [3] 0 0
Other collaborator category [4] 0 0
Other
Name [4] 0 0
National Marrow Donor Program
Address [4] 0 0
Country [4] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00412360
Trial related presentations / publications
Shulman HM, Sullivan KM, Weiden PL, McDonald GB, Striker GE, Sale GE, Hackman R, Tsoi MS, Storb R, Thomas ED. Chronic graft-versus-host syndrome in man. A long-term clinicopathologic study of 20 Seattle patients. Am J Med. 1980 Aug;69(2):204-17. doi: 10.1016/0002-9343(80)90380-0.
Public notes

Contacts
Principal investigator
Name 0 0
Mary Horowitz, MD, MS
Address 0 0
Center for International Blood and Marrow Transplant Research
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00412360