A Single-Arm, Open-Label, Multi-Centre, Phase Ib Study Evaluating the Safety and Preliminary Efficacy of AUTO1 in Pediatric Patients With CD19-Positive Relapsed/ Refractory (r/r) B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B Cell Non-Hodgkin Lymphoma (B NHL)
This is a Phase Ib study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 in pediatric patients with relapsed or refractory (r/r) B cell acute lymphoblastic leukemia (B ALL) and r/r B cell Non-Hodgkin lymphoma (B NHL)
• Male or female patients \< 18 years old at screening
• Patients with ≥ 6 kg body weight at screening
⁃ B ALL Cohort: r/r CD19-positive B ALL defined as:
⁃ Primary refractory disease defined as:
• National Cancer Institute high risk (defined as presenting with white blood cell count ≥ 50 × 10\^9 cells/L or aged ≥ 10 years at diagnosis) patients with MRD ≥ 0.01% after first-line induction and consolidation and blinatumomab (if allowed per country specific approvals and treatment guidelines).
∙ Refractory B ALL if BM disease ≥ 25% after first line induction and consolidation.
∙ KMT2A rearranged infant ALL with MRD ≥ 1% after first line induction and blinatumomab (if allowed per country specific approvals and treatment guidelines) or MRD ≥ 0.01% after first line induction and consolidation.
⁃ First relapse
• Children's Oncology Group high risk first relapse involving BM \< 36 months after initial diagnosis or an isolated extramedullary relapse \< 18 months after initial diagnosis.
∙ Patients with Down syndrome and infants with KMT2A rearranged are eligible with first relapse at any time.
∙ Refractory disease with MRD ≥ 0.01% after re-induction for first relapse (with or without blinatumomab, if allowed per country specific approvals and treatment guidelines).
⁃ Second or greater relapse
⁃ Relapsed or refractory post-SCT:
⁃ a. Relapsed or refractory disease after allogeneic transplant provided obe cel infusion occurs ≥ 3 months after SCT.
⁃ Philadelphia chromosome positive (Ph+) ALL:
• Any of the above with Ph+ ALL where patient is intolerant to or has failed at least one tyrosine kinase inhibitor (TKI) or if TKI therapy is contraindicated.
⁃ B NHL Cohort: r/r CD19-positive aggressive mature B NHL defined as 1 of the following:
⁃ Relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic SCT).
⁃ Primary refractory (have not achieved a CR or PR after the first line of therapy) with measurable, disease by radiological criteria at screening including the B NHL subtypes: (i) diffuse large B-cell lymphoma (DLBCL), (ii) Burkitt's lymphoma, (iii) primary mediastinal large B-cell lymphoma (PMBCL) and (iv) high-grade B-cell lymphoma (not otherwise specified).
∙ Karnofsky (age ≥ 10 years) or Lansky (age \< 10 year) performance status score ≥ 50%.
‣ In patients with B ALL, local documentation of CD19 expression on leukemic blasts in the BM, peripheral blood, or cerebrospinal fluid (CSF) or biopsy done no more than 30 days prior to consent. In patients treated with blinatumomab, testing should be undertaken after blinatumomab therapy has been stopped. In patients with mature B NHL, CD19 expression must be confirmed in a biopsy after any CD19 targeted therapies.
‣ Adequate renal, hepatic, pulmonary, and cardiac function.