Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)



Status:Completed
Conditions:Cancer, Blood Cancer, Hematology
Therapuetic Areas:Hematology, Oncology
Healthy:No
Age Range:1 - 21
Updated:5/5/2018
Start Date:December 2006
End Date:October 2014

Use our guide to learn which trials are right for you!

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)

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.

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.

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
We found this trial at
37
sites
1600 SW Archer Rd # M509
Gainesville, Florida 32610
?
mi
from
Gainesville, FL
Click here to add this to my saved trials
700 Childrens Drive
Columbus, Ohio 43205
(616) 722-2000
Nationwide Children's Hospital At Nationwide Children’s, we are creating the future of pediatric health care....
?
mi
from
Columbus, OH
Click here to add this to my saved trials
Denver, Colorado 80218
?
mi
from
Denver, CO
Click here to add this to my saved trials
807 Childrens Way
Jacksonville, Florida 32207
(904) 697-3600
Nemours Children's Clinic At Nemours Children’s Clinic, Jacksonville, we've treated every child as we would...
?
mi
from
Jacksonville, FL
Click here to add this to my saved trials
Miami, Florida 33124
(305) 284-2211
University of Miami A private research university with more than 15,000 students from around the...
?
mi
from
Miami, FL
Click here to add this to my saved trials
Minneapolis, Minnesota 55455
(612) 625-5000
Univ of Minnesota With a flagship campus in the heart of the Twin Cities, and...
?
mi
from
Minneapolis, MN
Click here to add this to my saved trials
1211 Medical Center Dr
Nashville, Tennessee 37232
(615) 322-5000
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
?
mi
from
Nashville, TN
Click here to add this to my saved trials
South 34th Street
Philadelphia, Pennsylvania 19104
 215-590-1000
Children's Hospital of Philadelphia Since its start in 1855 as the nation's first hospital devoted...
?
mi
from
Philadelphia, PA
Click here to add this to my saved trials
1100 Fairview Avenue North
Seattle, Washington 98109
(206) 667-5000
Fred Hutchinson Cancer Research Center At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of...
?
mi
from
Seattle, WA
Click here to add this to my saved trials
40 Sunshine Cottage Road
Valhalla, New York 10595
(914) 594-4000
New York Medical College The College was founded in 1860 by a group of New...
?
mi
from
Valhalla, NY
Click here to add this to my saved trials
Ann Arbor, Michigan 48109
?
mi
from
Ann Arbor, MI
Click here to add this to my saved trials
1405 Clifton Road NE
Atlanta, Georgia 30322
404-785-6000
Children's Healthcare of Atlanta Whether treating a toddler in an emergency or supporting a teen...
?
mi
from
Atlanta, GA
Click here to add this to my saved trials
Birmingham, Alabama 35294
?
mi
from
Birmingham, AL
Click here to add this to my saved trials
Boston, Massachusetts 02114
?
mi
from
Boston, MA
Click here to add this to my saved trials
171 Ashley Avenue
Charleston, South Carolina 29425
843-792-1414
Medical University of South Carolina The Medical University of South Carolina (MUSC) has grown from...
?
mi
from
Charleston, SC
Click here to add this to my saved trials
1935 Medical District Dr
Dallas, Texas 75235
(214) 456-7000
Children's Medical Center of Dallas Children's Medical Center is private, not-for-profit, and is the fifth-largest...
?
mi
from
Dallas, TX
Click here to add this to my saved trials
?
mi
from
Detroit, MI
Click here to add this to my saved trials
1500 East Duarte Road
Duarte, California 91010
626-256-HOPE (4673)
City of Hope National Medical Center City of Hope is dedicated to making a difference...
?
mi
from
Duarte, CA
Click here to add this to my saved trials
2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
?
mi
from
Durham, NC
Click here to add this to my saved trials
801 7th Avenue
Fort Worth, Texas 76104
(682) 885-4000
Cook Children's Medical Center Cook Children's Health Care System is a not-for-profit, nationally recognized pediatric...
?
mi
from
Fort Worth, TX
Click here to add this to my saved trials
545 Barnhill Dr
Indianapolis, Indiana 46201
(317) 274-8157
Indiana University Medical Center Indiana University Health is Indiana
?
mi
from
Indianapolis, IN
Click here to add this to my saved trials
Jackson, Mississippi 39216
?
mi
from
Jackson, MS
Click here to add this to my saved trials
Kansas City, Missouri 64108
?
mi
from
Kansas City, MO
Click here to add this to my saved trials
?
mi
from
Louisville, KY
Click here to add this to my saved trials
8701 W Watertown Plank Rd
Milwaukee, Wisconsin
(414) 955-8296
Medical College of Wisconsin The Medical College (MCW) of Wisconsin is a major national research...
?
mi
from
Milwaukee, WI
Click here to add this to my saved trials
New Orleans, Louisiana 70118
?
mi
from
New Orleans, LA
Click here to add this to my saved trials
Oakland, California 94609
?
mi
from
Oakland, CA
Click here to add this to my saved trials
1919 E Thomas Rd
Phoenix, Arizona 85006
(602) 933-1000
Phoenix Children's Hospital Phoenix Children's Hospital has provided hope, healing, and the best healthcare for...
?
mi
from
Phoenix, AZ
Click here to add this to my saved trials
Portland, Oregon 97227
?
mi
from
Portland, OR
Click here to add this to my saved trials
Richmond, Virginia 23298
?
mi
from
Richmond, VA
Click here to add this to my saved trials
Saint Petersburg, Florida 33701
?
mi
from
Saint Petersburg, FL
Click here to add this to my saved trials
Salt Lake City, Utah 84132
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
San Antonio, Texas 78229
?
mi
from
San Antonio, TX
Click here to add this to my saved trials
San Diego, California 92123
?
mi
from
San Diego, CA
Click here to add this to my saved trials
San Francisco, California 94143
?
mi
from
San Francisco, CA
Click here to add this to my saved trials
111 Michigan Ave NW
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
?
mi
from
Washington,
Click here to add this to my saved trials
Westmead, New South Wales 2145
?
mi
from
Westmead,
Click here to add this to my saved trials