Phase I/II Dose Escalation and Preliminary Efficacy of CD19 Directed CAR-T Cells Generated Using the Miltenyi CliniMACs Prodigy System (UCD19 CAR-T) in Pediatric Patients With Relapsed and/or Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL) and B-Cell Non-Hodgkin Lymphoma (B-NHL)
This phase I/II trial will investigate a new CD19 directed CAR-T therapy manufactured locally with the goals to expedite infusion to wider patient inclusion that includes those who were previously excluded, such as pediatric patients with B-cell NHL and patients in primary relapse.
• Meets clinical criteria for leukapheresis or has a leukapheresis product previously collected and stored per recommended guidelines.
• Provision of signed and dated consent form from parent or guardian (patients \<18), the patient themselves (\>18), or legally authorized representative (patient \>18 who lack decision-making capacity); Pediatric patients will be included in age-appropriate discussions and assent will be obtained for those \> 7 years of age, when appropriate, according to institutional standards.
• Willingness to participate in long term follow up study.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Males OR non-pregnant, non-breastfeeding females.
• o Patients of child-bearing potential or capable of fathering a child must agree to use highly effective contraception from the time of initial CAR T cell administration though 12 months following the final administration of investigational product.
• Aged 31 days to 30 years (inclusive) at time of consent and enrollment.
• Acute Lymphoblastic Leukemia (ALL) OR Non-Hodgkin Lymphoma (NHL) of B-cell origin that:
• o Has confirmed expression of CD19 by flow cytometry, immunohistochemistry (IHC), or both.
• Cohort One Criteria:
⁃ Meets any one of the following conditions:
∙ Relapsed two or more times
‣ Relapsed at any time after allogeneic BMT
‣ Refractory to standard therapy as determined by the treating physician
‣ Meets criteria for BMT but is ineligible as determined by the treating physician
‣ Patient and/or parents declining BMT options and would prefer CAR-T Therapy.
⁃ Non-Hodgkin Lymphoma includes all of the following:
∙ Diffuse large B-cell lymphoma (DLBCL)
‣ Burkitt Lymphoma
‣ Intermediate lymphoma between Burkitt and DLBCL
‣ Primary Mediastinal B-cell Lymphoma (PMBL)
‣ Follicular lymphoma
‣ High grade B cell lymphoma
‣ Transformed lymphoma
• Cohort Two Criteria:
⁃ B-ALL in first relapse with any one of the following conditions:
∙ High-risk genomic alterations at initial diagnosis such as KMT2A gene rearrangement, t(17;19), hypodiploidy, Ph-like mutations, BCR-ABL1 fusion (Ph+ ALL), iAMP21, and TP53 inactivating mutation/deletion.
‣ Isolated CNS relapse such that cranial radiation would be indicated as a component of standard salvage therapy.
‣ Down syndrome.
‣ Minimal residual disease (MRD) positivity of \> 0.01% by FACS or \> 0 clonal sequences by NGS in bone marrow post re-induction chemotherapy.
‣ Age 18 years or older. OR
⁃ Newly diagnosed with persistent MRD ≥ 0.01% by flow cytometry in bone marrow at end of consolidation.
• Performance score (Lansky or Karnofsky) of 50% or better;
• Unable to or declined to receive commercially available CD19 CAR-T Therapy.