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

• Status: Completed
• Trial end date: 2014-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Medical College of Wisconsin
• Collaborators: Blood and Marrow Transplant Clinical Trials Network; National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI); National Marrow Donor Program
• Treatments: Cyclophosphamide; Cyclosporine; Cyclosporins; Fludarabine; Fludarabine phosphate; Mycophenolate mofetil; Mycophenolic Acid; Vidarabine; Vidarabine Phosphate

Criteria

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