Status:
TERMINATED
Combined T Cell Depleted Haploidentical Peripheral Blood Stem Cell and Unrelated Umbilical Cord Blood Transplantation in Patients With Hematologic Malignancies Using a Total Lymphoid Irradiation Based Preparative Regimen
Lead Sponsor:
St. Jude Children's Research Hospital
Conditions:
Hematological Malignancies
Eligibility:
All Genders
Up to 21 years
Phase:
PHASE2
Brief Summary
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who do not have a suitable human leukocyte antigen (HLA)-matched related/siblin...
Detailed Description
Prior to stem cell infusion, participants will receive a preparative regimen of total lymphoid irradiation (TLI), fludarabine, cyclophosphamide, melphalan, and thiotepa to prepare their bone marrow. T...
Eligibility Criteria
Inclusion
- Inclusion Criteria-Transplant Recipient:
- Age less than or equal to 21 years old.
- Does not have a suitable matched related/sibling donor (MSD) or volunteer matched unrelated donor (MUD) available in the necessary time for stem cell donation.
- Has a suitable partially human leukocyte antigen (HLA)-matched (≥ 3 of 6) family member donor.
- Has a partially HLA-matched single umbilical cord blood (UCB) unit (≥ 4 of 6) with adequate cell dose. UCB units must fulfill eligibility as outlined in 21 CFR 1271 and agency guidance.
- High-risk hematologic malignancy.
- High risk acute lymphocytic leukemia (ALL) in complete remission-1 (CR)1. \[Examples include, but not limited to t(9;22), hypodiploid,, M2 or greater marrow at the end of induction, infants with mixed lineage leukemia (MLL) fusion or t(4;11)\].
- ALL in High risk CR2. \[Examples include but not limited to t(9;22), bone marrow (BM) relapse \<36 mo CR1, T-ALL, very early (\< 6mo CR1) isolated central nervous system (CNS) relapse.\]
- ALL in CR3 or subsequent.
- Acute myeloid leukemia (AML) in high risk CR1. \[Examples include but not limited to preceding MDS, 5q-, -5, -7, FAB M6, FAB M7 not t(1;22), minimal residual disease (MRD) ≥ 5% on day 22 (AML08), M3 marrow after induction 1, M2 marrow after two cycles of induction, FLT3-ITD.\]
- AML in CR2 or subsequent.
- Therapy related AML, with prior malignancy in CR \> 12mo
- Myelodysplastic syndrome (MDS), primary or secondary
- Natural killer (NK) cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
- Chronic myeloid leukemia (CML) in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor.
- Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous hematopoietic cell transplantation (HCT), or unable to mobilize stem cells for autologous HCT.
- Non-Hodgkin lymphoma in CR2 or subsequent.
- Juvenile myelomonocytic leukemia (JMML).
- Refractory hematologic malignancies \[ALL, AML, chronic myeloid leukemia (CML) in blast crisis, Hodgkin or non-Hodgkin lymphoma\] due to chemoresistant relapse or primary induction failure.
- All patients with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for study.
- Patient must fulfill pre-transplant evaluation:
- Cardiac Function: Left ventricular ejection fraction (LVEF) ≥ 40% or shortening fraction (SF) ≥ 25%.
- Creatinine clearance (CrCL) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2.
- Forced vital capacity (FVC) ≥ 50% of predicted value or pulse oximetry (Pox) ≥ 92% on room air.
- Karnofsky or Lansky performance score ≥ 50.
- Bilirubin ≤ 3 times the upper limit of normal for age.
- Alanine aminotransferase (ALT) ≤ 5x the upper limit of normal for age.
- Aspartate aminotransferase (AST) ≤ 5x the upper limit of normal for age.
- Exclusion Criteria - Transplant Recipient:
- Patient has a suitable MSD, volunteer matched unrelated donor (MURD), or killer-immunoglobulin receptors (KIR) mismatched haploidentical donor available in the necessary time for stem cell donation.
- Patient has any other active malignancy other than the one for which HCT is indicated.
- Patient is pregnant as confirmed by positive serum or urine pregnancy test within 14 days prior to enrollment.
- Patient is breast feeding.
- Patient has Down Syndrome.
- Patient has a current uncontrolled bacterial, fungal, or viral infection per the judgment of the principal investigator.
- Inclusion criteria - haploidentical donor
- At least single haplotype matched (≥ 3 of 6) family member
- At least 18 years of age.
- Human immunodeficiency virus (HIV) negative.
- Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment (if female).
- Not breast feeding.
- Regarding eligibility, is identified as either:
- Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
- Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271.
Exclusion
Key Trial Info
Start Date :
July 11 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 23 2017
Estimated Enrollment :
24 Patients enrolled
Trial Details
Trial ID
NCT02199041
Start Date
July 11 2014
End Date
May 23 2017
Last Update
February 7 2018
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105