Overview
The purpose of this study is to learn more about newer methods of transplanting blood cells donated by a partially matched family member to children with high-risk CD19 positive leukemia ALL.
Primary Objective:
\- To assess the safety and feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
Secondary Objectives:
- To estimate 1-year post-transplant overall survival, event-free survival, and GVHD-free relapse-free survival (GRFS).
- To estimate cumulative incidence of engraftment, acute and chronic GVHD, and immune-related adverse events, including CRS and ICANS.
Description
This is a Phase I study evaluating the addback of CD19-CAR(Mem) T cells after TCRαβ+/CD19 B cell depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
Donors that meet eligibility criteria will be consented to undergo two separate collections: 1) G-CSF mobilized stem cell graft via apheresis for progenitor cell infusion and 2) Non-mobilized peripheral blood mononuclear cells (PBMC) via apheresis for subsequent CAR T-cell manufacturing and DLI if needed.
Patients that meet eligibility criteria to receive therapy will be consented to proceed on study. Treatment will include a conditioning chemotherapy preparative regimen followed by infusion of TCRαβ/CD19 B cell depleted progenitor cell infusion on day 0. Then as early as day + 14 patients will receive the previously manufactured CD19-CAR(Mem) T cell product. Patients will then be monitored for safety and efficacy of the infused CAR T-cell product, as well as collection of correlative samples.
Eligibility
Inclusion Criteria:
Recipient
- Age less than or equal to 21 years
- High risk hematologic malignancy where allogeneic transplantation is the current standard of care. This includes (but is not limited to):
- High risk CD19+ B cell ALL in CR1 or CR2
- Any CD19+ B-cell ALL in CR3 or subsequent
- If prior CNS leukemia, it must be treated and in CNS CR
- 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
Donor
- At least single haplotype matched (≥ 4 of 8) family member
- At least 18 years of age
- HIV negative
- If sexually active, agreement to use birth control until 2 weeks after completion of the mobilization and apheresis procedure
- 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:
Recipient
- Has a suitable HLA-identical sibling or suitable 12/12 (HLA-A, B, C, DRB1, DQB1, and DPB1) HLA-matched unrelated donor available in an appropriate time frame
- Any other active malignancy other than the one for which this HCT is indicated
- Received a prior allogeneic HCT at any time
- Pregnant, if female is of childbearing potential, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment
- If sexually active, agreement to use birth control until 6 months after T cell infusion
- Breast feeding
- Any severe current uncontrolled bacterial, fungal or viral infection
Donor
- Pregnant, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment if female
- If female, breast feeding
