Clinical trial NCT02007863: Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia
Official title: Treatment Protocol: Umbilical Cord Blood (UCB) Transplantation in Pediatric Patients With High Risk Leukemia and Myelodysplasia Using Conditioning Regimen Without Radiation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Leukemia
Myelodysplasia
Acute Lymphocytic Leukemia
Acute Myelogenous Leukemia
Keywords: Leukemia
Myelodysplasia
Acute lymphocytic leukemia
ALL
Acute myelogenous leukemia
AML
Pediatric
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2013-12-11
Enrollment: 2
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Unrelated Cord Blood (UCB) transplant in children is a viable stem cell transplant modality for patients with leukemia and myelodysplasia. UCB is now considered "Standard Of Care" in cases where a suitable living bone marrow donor is not available. The survival of UCB is similar to Matched Unrelated Marrow Transplant. This study is considered "Research" since UCB is not a licensed product and requires investigational new drug (IND). THERE ARE NO SPECIFIC RESEARCH QUESTIONS IN THIS PROTOCOL. This protocol merely provides UCB as a stem cell treatment modality to pediatric patients who may require it after a conditioning regimen that excludes Total Body Irradiation.

Detailed description: The preparative regimen will consist of:

* Fludarabine: 25 mg/m2/day IV x 5 doses on Days -13, to -9
* Busulfan 1mg/kg IV every 6 hrs x 16 doses on Days -8 to -5
* Melphalan 45 mg/m2/day IV x 3 doses on days -4 to -2
* ATGAM 30mg/kg/day x 3 doses on Days -3 to -1
* Day 0 will be the day of the UCB Transplant
* The graft-versus-host-disease (GVHD) prophylaxis will be Cyclosporin A to maintain level 200-400 beginning on Day -3, through 200-400. Solumedrol at 1mg/kg/day on Day 1 until D+4, then solumedrol 2mg/kg/day until Day +19 or till absolute neutrophil count (ANC) reaches 500/mm2, then taper by 0.2 mg/kg/week.

Eligibility criteria: Inclusion Criteria:

* Patients must be up to 21 years of age
* Patients cannot receive total body irradiation (TBI) because of:

  * Young age - \< 2 years at diagnosis of leukemia resulting in an age \< 4 years at transplantation (due to risk of severe growth retardation and brain damage).
  * Inability to tolerate TBI because of prior radiation or organ toxicity.
  * Refractory/multiply relapsed leukemia, for which a traditional TBI/cyclophosphamide regimen would unlikely lead to a successful outcome.
* Patients must have a partially human leukocyte antigen (HLA)-matched UCB unit. Unit 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. The unit must deliver a pre-cryopreserved nucleated cell dose of at least 2.5 x 10\^7 per kilogram.
* Acute myelogenous leukemia (AML) at the following stages:

  * High risk first complete remission (CR1), defined as:

    * Having preceding myelodysplasia (MDS)
    * High risk cytogenetics (High-risk cytogenetics: del (5q) -5, -7, abn (3q), t (6;9) complex karyotype (\>= 5 abnormalities)
    * Requiring \> 2 cycles chemotherapy to obtain CR;
  * Second or greater CR.
  * First relapse with \< 25% blasts in bone marrow.
* Patients with therapy-related AML whose prior malignancy has been in remission for at least 12 months.
* Acute lymphocytic leukemia (ALL) at the following stages:
* High risk first remission, defined as:

  1. Ph+ ALL; or,
  2. Myeloid/lymphoid leukemia (MLL) rearrangement with slow early response \[defined as having M2 (5-25% blasts) or M3 (\>25% blasts on bone marrow examination on Day 14 of induction therapy)\]; or,
  3. Hypodiploidy (\< 44 chromosomes or DNA index \< 0.81); or,
  4. End of induction M3 bone marrow; or,
  5. End of induction M2 with M2-3 at Day 42.
* High risk second remission, defined as:

  1. Bone marrow relapse \< 36 months from induction; or,
  2. T-lineage relapse at any time; or,
  3. Very early isolated central nervous system (CNS) relapse (6 months from diagnosis); or,
  4. Slow reinduction (M2-3 at Day 28) after relapse at any time.
* Any third or subsequent CR.
* Biphenotypic or undifferentiated leukemia in any CR or if in 1st relapse must have \< 25% blasts in bone marrow (BM).
* 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 must have a Karnofsky score ≥ 70% and patients \< 16 years old must have a Lansky score ≥ 70%.
* Signed informed consent.
* Patients with adequate physical function as measured by:

  1. Cardiac: Left ventricular ejection fraction at rest must be \> 40%, or shortening fraction \> 26%
  2. Hepatic: Bilirubin ≤ 2.5 mg/dL; and alanine transaminase (ALT), aspartate transaminase (AST) and Alkaline Phosphatase ≤ 5 x upper limit of normal (ULN)
  3. Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) \> 70 mL/min/1.73 m2.
  4. Pulmonary: Diffusing capacity of the lungs for carbon monoxide (DLCO), Forced expiratory volume in 1 second (FEV1), Forced vital capacity (FVC) (diffusion capacity) \> 50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then O2 saturation \> 92% of room air.

Exclusion Criteria:

* Pregnant (B-positive 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 \< 6 months prior to enrollment.
* Prior autologous transplant for the disease for which the UCB transplant will be performed.
* Allogeneic hematopoietic stem cell transplant \< 6 months prior to enrollment.
* Active malignancy other than the one for which the UCB transplant is being performed within 12 months of enrollment
* Active CNS leukemia.
* Requirement of supplemental oxygen.
* HLA-matched related donor able to donate.

Primary outcomes:
measure: Number of Successful Unrelated Cord Blood (UCB) Transplants
timeFrame: 2 Years
Secondary outcomes:
Other outcomes:
Locations:
city: Miami
country: United States
facility: Jackson Memorial Hospital
state: Florida
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
Study officials:
affiliation: University of Miami
name: Martin Andreasky, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: