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)
- Conditions
- B-cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B-cell Non-Hodgkin Lymphoma (B NHL).MedDRA version: 21.0Level: LLTClassification code: 10000844Term: Acute lymphoblastic leukaemia Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-506307-26-00
- Lead Sponsor
- Autolus Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 24
Male or female participants < 18 years old at screening, Patients with =6 kg body weight at screening, Willing and able to give written, informed consent to the current study (participant and/or parent or legal guardian)., Agreement to have a pregnancy test and use adequate contraception (if applicable)., Patients with diagnosis of: a. B ALL: r/r CD19-positive B ALL defined as one of the following: i. Primary refractory disease including: a) 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. b) COG intermediate risk cytogenetics with MRD = 1% EOI as assessed by flow cytometry. c) COG good risk cytogenetics with = 5% disease EOI as assessed. d) Down syndrome with MRD = 0.01% EOC as assessed by flow cytometry. e) High risk infant ALL (MRD-positive disease as assessed by flow cytometry post induction and blinatumomab) ii. COG very high risk (VHR) first relapse if first remission = 18 months. iii. Relapsed or refractory disease after two or more lines of systemic therapy. iv. Relapsed or refractory disease after allogeneic transplant provided AUTO1 infusion occurs = 3 months after stem cell transplant. v. 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. OR b. B NHL: r/r CD19-positive aggressive mature B NHL defined as one of the following: i. Relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic stem cell transplant) ii. 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 following B NHL subtypes: i. Diffuse large B cell lymphoma (DLBCL) ii. Burkitt’s lymphoma (BL) iii. Primary mediastinal large B cell lymphoma (PMBCL) iv. High-grade B cell lymphoma not otherwise specified (NOS)., 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.
Chronic myelogenous leukemia lymphoid in blast crisis., History or presence of clinically relevant 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., History or presence of active or latent Hepatitis B virus or active Hepatitis C virus., History of human immunodeficiency virus (HIV), human T cell lymphotropic virus (HTLV)-1, HTLV-2, or syphilis positive test., Prior CD19 targeted therapy other than blinatumomab., Patients who have experienced = Grade 3 neurotoxicity following blinatumomab.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the safety and tolerability of AUTO1 in relapsed/refractory B-ALL and B-NHL;Secondary Objective: To evaluate the preliminary clinical efficacy of AUTO1 in pediatric participants, To evaluate the feasibility of manufacturing and administering AUTO1 to pediatric participants, To evaluate the expansion and persistence of AUTO1, To evaluate the duration of B cell aplasia;Primary end point(s): Frequency and severity of adverse events (AEs) and serious adverse events (SAEs), Incidence and duration of severe Hypogammaglobulinemia
- Secondary Outcome Measures
Name Time Method Secondary end point(s):B-ALL Cohort: • Overall response rate (CR + CRi) • Proportion of patients achieving CR • Duration of remission (DoR); • Event free survival (EFS); • Proportion of patients achieving MRD-negative remission in BM; • Overall survival (OS); • Proportion of patients undergoing stem cell transplantation after AUTO1 infusion prior to relapse; • Incidence of CD19-negative relapse.;Secondary end point(s):B-NHL Cohort: • ORR (CR + PR) • Duration of response (DoR); • Progression free survival (PFS); • Overall survival (OS); • Incidence of CD19-negative relapse.