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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT00412360
Ethics application status
Date submitted
14/12/2006
Date registered
18/12/2006
Date last updated
3/05/2018

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
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
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

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 - Overall survival is defined as survival of death from any cause.
Timepoint [1] 0 0
1 year post-randomization
Secondary outcome [1] 0 0
Percentage of Participants With Disease-free Survival - Disease-free survival is defined as survival without relapse of the primary disease.
Timepoint [1] 0 0
1 year post-randomization
Secondary outcome [2] 0 0
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.
Timepoint [2] 0 0
Days 42 and 100
Secondary outcome [3] 0 0
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.
Timepoint [3] 0 0
2 years post-transplant
Secondary outcome [4] 0 0
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
Rash <25% of body surface area
Rash on 25-50% of body surface area
Rash on > 50% of body surface area
Generalized erythroderma with bullous formation
Liver stage (based on bilirubin level)*:
0: <2 mg/dL
2-3 mg/dL
3.01-6 mg/dL
6.01-15.0 mg/dL
>15 mg/dL
GI stage*:
0: No diarrhea or diarrhea <500 mL/day
Diarrhea 500-999 mL/day or persistent nausea with histologic evidence of GVHD
Diarrhea 1000-1499 mL/day
Diarrhea >1500 mL/day
Severe abdominal pain with or without ileus * If multiple etiologies are listed for liver or GI, the organ system is downstaged by 1.
GVHD grade:
0: All organ stages 0 or GVHD not listed as an etiology I: Skin stage 1-2 and liver and GI stage 0 II: Skin stage 3 or liver or GI stage 1 III: Liver stage 2-3 or GI stage 2-4 IV: Skin or liver stage 4
Timepoint [4] 0 0
Day 100 post-randomization
Secondary outcome [5] 0 0
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.
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 - 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.
Timepoint [7] 0 0
1 year post-randomization
Secondary outcome [8] 0 0
Percentage of Participants With Treatment-related Mortality - Treatment related mortality is defined as death without relapse of the primary disease.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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Arizona
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United States of America
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California
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United States of America
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Colorado
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United States of America
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District of Columbia
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United States of America
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Florida
Country [7] 0 0
United States of America
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Georgia
Country [8] 0 0
United States of America
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Indiana
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United States of America
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Kentucky
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United States of America
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Louisiana
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Massachusetts
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United States of America
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Michigan
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Minnesota
Country [14] 0 0
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Mississippi
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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
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United States of America
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South Carolina
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Tennessee
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Texas
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Utah
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Virginia
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Washington
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United States of America
State/province [27] 0 0
Wisconsin
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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/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.
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
Other publications