UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL

Más betegség

• Evidence of rapidly progressive disease without adequate salvage/bridging regimens as determined by the investigator.
• Active Graft-versus-Host Disease (GvHD).
• Active, uncontrolled, life-threatening infection that at the determination of the treating physician would preclude safe leukapheresis or tolerance of LD chemotherapy, cell infusion, or cytokine release syndrome.
• Known HIV infection, or active Hepatitis B or active Hepatitis C infection.

Laborértékek

• Evidence of severe organ dysfunction as defined by:
  • Myocardial dysfunction: Ejection fraction ≤ 40% or shortening fraction ≤ 28%, evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and clinically significant electrocardiogram (ECG) findings.
  • Baseline oxygen saturation of ≤ 90% on room air
  • Transaminases > 10x upper limit of normal (ULN) or bilirubin >2x the ULN, unless thought to be related to primary disease
  • Estimated Cr clearance <60 mL/min/1.73 m2 (if nuclear medicine GFR or other more specific testing exceeds this level than it can supersede the estimated clearance)

Egyéb

• Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration.

• 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:
  • 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.