Status:
ACTIVE_NOT_RECRUITING
TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies
Lead Sponsor:
St. Jude Children's Research Hospital
Conditions:
Acute Lymphoblastic Leukemia (ALL)
Acute Myeloid Leukemia (AML)
Eligibility:
All Genders
Up to 21 years
Phase:
PHASE2
Brief Summary
Patients less than or equal to 21 years old with high-risk hematologic malignancies who would likely benefit from allogeneic hematopoietic cell transplantation (HCT). Patients with a suitable HLA matc...
Detailed Description
In this study, participants with high-risk hematologic malignancies undergoing hematopoietic cell transplantation (HCT), who lack an available suitable human leukocyte antigen (HLA) matched related/si...
Eligibility Criteria
Inclusion
- Inclusion Criteria for Transplant Recipient
- Age less than or equal to 21 years.
- Does not have a suitable HLA-matched sibling donor (MSD) or volunteer 10/10 HLA-matched unrelated donor (MUD) available in the necessary time for progenitor cell donation.
- Has a suitable single haplotype matched (≥ 3 of 6) family member donor.
- High risk hematologic malignancy. High risk ALL in CR1. Examples include, but not limited to: t(9;22) with persistent or recurrent transcript, hypodiploid cytogenetics, MRD \>1% at the end of induction, M2 or greater marrow at the end of induction, recurrent or rising MRD after induction, Infants with MLL fusion or t(4;11), relapse after prior CART therapy.
- ALL in High risk CR2. Examples include, but not limited to t(9;22), BM relapse \<36 mo CR1 or \<6mo after completion of therapy, any T-ALL, very early (\< 6mo CR1) isolated CNS relapse, late BM relapse with poor response to standard reinduction therapy(e.g. MRD positive or recurrence after two blocks), relapse after prior CART therapy.
- ALL in CR3 or subsequent.
- AML in high risk CR1 (diagnosis of AML includes myeloid sarcoma). Examples include but not limited to: preceding MDS or MDS-related AML, FAB M0, FAB M6, FAB M7 with high risk genetics such as ML not t(1;22), MRD \> 0.1% after two cycles of induction, MRD \> 1% after one cycle of induction, FLT3-ITD in combination with NUP98-NSD1 fusion or WT1 mutation, any high risk cytogenetics such as: DEK-NUP214 \[t(6;9)\], KAT6A-CREBBP \[t(8;16)\], RUNX1-CBFA2T3 \[t(16;21)\], -7, -5, 5q-, KMT2A-MLLT10 \[t(6;11)\], KMT2A-MLLT4 \[t(10;11)\], inv(3)(q21q26.2), CBFA2T3-GLIS2 \[inv(16)(p13.3q24.3)\], NUP98-KDM5A \[t(11;12)(p15;p13)\], ETV6-HLXB \[t(7;12)(q36;p13)\], NUP98-HOXA9 \[t(7;11)(p15.4;p15)\], NUP98-NSD1.
- AML in CR2 or subsequent.
- Therapy related AML, with prior malignancy in CR \> 12mo
- MDS, primary or secondary
- NK cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
- 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 HCT, or unable to mobilize progenitor cells for autologous HCT.
- Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize progenitor cells for autologous HCT.
- JMML
- If prior CNS leukemia, it must be treated and in CNS CR
- Does not have any other active malignancy other than the one for which this HCT is indicated.
- No prior allogeneic HCT, and no autologous HCT within the previous 12 months.
- Patient must fulfill pre-transplant organ function criteria:
- Left ventricular ejection fraction \> 40%, or shortening fraction ≥ 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 ≥ 92% on room air if patient is unable to perform pulmonary function testing.
- Karnofsky or Lansky (age-dependent) performance score ≥ 50 (See APPENDIX A).
- Bilirubin ≤ 3 times the upper limit of normal for age.
- Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age.
- Not pregnant. If female with child bearing potential, must be confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment.
- Not breast feeding
- Does not have current uncontrolled bacterial, fungal, or viral infection.
- Inclusion Criteria for Haploidentical Donor
- At least single haplotype matched (≥ 3 of 6) family member
- At least 18 years of age.
- 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 donation 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 Criteria:
- \-
Exclusion
Key Trial Info
Start Date :
January 31 2019
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
August 7 2025
Estimated Enrollment :
140 Patients enrolled
Trial Details
Trial ID
NCT03849651
Start Date
January 31 2019
End Date
August 7 2025
Last Update
February 25 2025
Active Locations (1)
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1
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105