Overview
This is a Phase Ib study to evaluate the safety and efficacy of autologous T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 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)
Description
This is a single-arm, open-label, multi-center, Phase Ib study to determine the safety and preliminary efficacy of AUTO1 administered intravenously in pediatric patients with r/r B ALL and with r/r aggressive mature B NHL. This study is designed to evaluate the safety and preliminary efficacy of AUTO1.
The safety and tolerability of AUTO1 in pediatric patients will be continually monitored by the Sponsor. Additionally, the Independent Data Monitoring Committee (IDMC) will review the rolling safety data generated after 6 and 12 treated patients have been monitored for at least 28 days and in the event any protocol defined safety stopping criteria are met. If no pre-defined safety events related to AUTO1 are met, and the safety data are consistent with what has previously been observed with AUTO1, the IDMC can recommend continuing the study without or with modifications. Based on emerging data, the study may be stopped early due to excessive toxicity, i.e. certain pre-defined AUTO1-related safety events or deaths.
The study will involve consented patients going through the following sequential study periods: screening, leukapheresis, bridging as necessary, lymphodepletion, treatment evaluation, and follow-up.
Eligibility
INCLUSION CRITERIA:
- 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 (NCI) high risk or Children's Oncology Group (COG) high risk patients with MRD ≥ 0.1% EOI (end of induction) or >0.01% at EOC (end of consolidation) as assessed by flow cytometry.
- COG intermediate risk cytogenetics with MRD ≥ 1% EOI as assessed by flow cytometry.
- COG good risk cytogenetics with ≥ 5% disease EOI as assessed by flow cytometry
- Down syndrome with MRD ≥ 0.01% EOC as assessed by flow cytometry.
- High risk infant ALL (MRD-positive disease as assessed by flow cytometry post induction and blinatumomab)
- Children's Oncology Group (COG) very high risk first relapse if first remission ≤18
months.
- Relapsed or refractory disease after two or more lines of systemic therapy.
- Relapsed or refractory disease after allogeneic transplant provided AUTO1 infusion occurs ≥3 months after stem cell transplant..
- Any of the above with Philadelphia chromosome positive disease (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:
- Relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic stem cell transplant)
- 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
- Adequate renal, hepatic, pulmonary, and cardiac function
EXCLUSION CRITERIA:
- Diagnosis of chronic myelogenous leukemia lymphoid in blast crisis
- History or presence of clinically relevant central nervous system (CNS) pathology
- Presence of CNS 3 disease or CNS 2 disease with neurological changes at screening
- Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management
- Patients who had prior (< 3 months before AUTO 1 infusion) stem cell transplant
- Prior CD19 targeted therapy other than blinatumomab
- Patients who have experienced ≥ Grade 3 neurotoxicity following blinatumomab