What's the purpose of this trial?
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 matched sibling or unrelated donor identified will be eligible for participation ONLY if the donor is not available in the necessary time.
The purpose of the study is to learn more about the effects (good and bad) of transplanting blood cells donated by a family member, and that have been modified in a laboratory to remove the type of T cells known to cause graft-vs.-host disease, to children and young adults with a high risk cancer that is in remission but is at high risk of relapse. This study will give donor cells that have been TCRαβ-depleted. The TCR (T-cell receptor) is a molecule that is found only on T cells. These T-cell receptors are made up of two proteins that are linked together. About 95% of all T-cells have a TCR that is composed of an alpha protein linked to a beta protein, and these will be removed. This leaves only the T cells that have a TCR made up of a gamma protein linked to a delta protein. This donor cell infusion will be followed by an additional infusion of donor memory cells (CD45RA-depleted) after donor cell engraftment.
This study will be testing the safety and effects of the chemotherapy and the donor blood cell infusions on the transplant recipient's disease and overall survival.
This trial is currently open and accepting patients.
What will happen during the trial?
You may be able to join this trial if you:
The following criteria is a partial list of reasons why patients may be
eligible to participate in this clinical trial. Further evaluation with a medical professional is
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.
* 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.
Additional Trial Information
Enrollment: 140 patients (estimated)