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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)


Phase 3
1 Year
21 Years
Open (Enrolling)
Both
Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Myelodysplastic Syndrome, NK Cell Lymphoblastic Leukemia

Thank you

Trial Information

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)


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 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.


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; ALT, AST and 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: DLCO, FEV1, FEC (diffusion capacity) 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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Time Frame:

1 year

Safety Issue:

No

Principal Investigator

Joseph Rosenthal, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope National Medical Center

Authority:

United States: Federal Government

Study ID:

467

NCT ID:

NCT00412360

Start Date:

December 2006

Completion Date:

May 2015

Related Keywords:

  • Acute Myelogenous Leukemia
  • Acute Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia
  • Myelodysplastic Syndrome
  • NK Cell Lymphoblastic Leukemia
  • Double cord blood
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

University of AlabamaBirmingham, Alabama  
Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Medical University of South CarolinaCharleston, South Carolina  29425-0721
Medical College of WisconsinMilwaukee, Wisconsin  53226
New York Medical CollegeValhalla, New York  10595
Children's National Medical CenterWashington, District of Columbia  20010-2970
All Children's HospitalSt. Petersburg, Florida  33701
Phoenix Children's HospitalPhoenix, Arizona  85016-7710
City of Hope National Medical CenterLos Angeles, California  91010
Nationwide Children's HospitalColumbus, Ohio  43205-2696
Vanderbilt University Medical CenterNashville, Tennessee  37232-2516
University of MinnesotaMinneapolis, Minnesota  55455
Children's Medical Center of DallasDallas, Texas  75235
Duke University Medical CenterDurham, North Carolina  27710
University of Michigan Medical CenterAnn Arbor, Michigan  48104-0914
Oregon Health Sciences UniversityPortland, Oregon  
Indiana University Medical CenterIndianapolis, Indiana  46202
Texas Transplant InstituteSan Antonio, Texas  78229
University of MiamiMiami, Florida  33136
Children's Healthcare of AtlantaAtlanta, Georgia  30342
University of Florida College of Medicine (Shands)Gainesville, Florida  32610
Utah BMT/University of Utah Medical SchoolSalt Lake City, Utah  84132
Nemours Childrens ClinicJacksonville, Florida  32207
DFCI/Children's Hospital of BostonBoston, Massachusetts  02114
University of MississippiJackson, Mississippi  39216
Childrens Hospital at OaklandOakland, California  94609
UCSD/Rady Childrens HospitalSan Diego, California  92123
University of California, San Francisco (Peds)San Francisco, California  94143
The Children's Hospital of DenverDenver, Colorado  80218
University of Louisville/Kosiar Children's HospitalLouisville, Kentucky  40202
Children's of New OrleansNew Orleans, Louisiana  70118
Karmanos Cancer Institute/Children's Hospital of MichiganDetroit, Michigan  48201
Children's Mercy Hospital and ClinicsKansas City, Missouri  64108
Cook Childrens Medical CenterForth Worth, Texas  76104
Virgina Commonwealth UniversityRichmond, Virginia  23298