Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia, Relapsed or Refractory B Cell Non-Hodgkin Lymphoma
Conditions
Keywords
B cell acute lymphoblastic leukemia, B cell Non-Hodgkin lymphoma, Relapsed B cell acute lymphoblastic leukemia, Relapsed B cell Non-Hodgkin lymphoma, Refractory B cell acute lymphoblastic leukemia, Refractory B cell Non-Hodgkin lymphoma, Aggressive mature B cell Non-Hodgkin lymphoma, Pediatric ALL, Pediatric NHL, Obecabtagene autoleucel, CD19-positive CAR T cell, Obe-cel
Brief summary
This is a Phase 1b/2 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).
Detailed description
This is a single-arm, open-label, multi-center, Phase 1b/2 study to determine the safety and efficacy of obe-cel administered intravenously in pediatric patients \< 18 years old with r/r B ALL and with r/r aggressive mature B NHL. The safety and tolerability of obe cel in pediatric patients will be continually monitored by the Sponsor. Efficacy endpoints will be determined by an Independent Response Review Committee (IRRC). The study will involve consented patients going through the following sequential study periods: screening, leukapheresis, bridging as necessary, lymphodepletion, treatment evaluation, and follow-up.
Interventions
BIOLOGICALAUTO1
Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with anti-CD19 chimeric antigen receptor (CAR) T cells
Sponsors
Autolus Limited
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
0 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* \< 18 years old at screening * ≥ 6 kg body weight at screening Pediatric patients with r/r B ALL r/r CD19-positive aggressive mature B including the B NHL subtypes: i) diffuse large B cell lymphoma, ii) Burkitt's lymphoma, iii) primary mediastinal large B cell lymphoma, iv) high-grade B cell lymphoma (not otherwise specified). * Karnofsky (age ≥ 10 years) or Lansky (age \< 10 year) performance status score ≥ 50%. * In participants with B ALL, local documentation of CD19 expression on leukemic blasts in the BM, peripheral blood, or cerebrospinal fluid 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 in lymphoid blast crisis. * History or presence of clinically relevant central nervous system (CNS) pathology unrelated to CNS leukemia. * Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management. * Received prior (\< 3 months before obe cel infusion) stem cell transplantation. * Prior CD19 targeted therapy other than blinatumomab. * Experienced Grade ≥ 3 neurotoxicity following blinatumomab.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) | Up to 24 months |
| Incidence and duration of severe hypogammaglobulinemia | Up to 24 months |
| Proportion of pediatric participants with r/r B ALL at screening who achieve complete remission (CR) within 3 months of obe-cel infusion per Independent Response Review Committee (IRRC) assessment | 3 months |
Secondary
| Measure | Time frame |
|---|---|
| CR per IRRC assessment at any time in B ALL | Up to 24 months |
| Overall remission rate (ORR) (CR + complete remission with incomplete recovery of counts [CRi]) per IRRC assessment at any time in B ALL | Up to 24 months |
| Minimal residual disease (MRD)-negative ORR per IRRC assessment at any time in B ALL | Up to 24 months |
| Event-free survival in B ALL | Up to 24 months |
| Overall survival (OS) in B ALL | Up to 24 months |
| ORR (CR or partial response [PR]) per Investigator assessment occurring at any time in B NHL | Up to 24 months |
| Duration of response in B NHL | Up to 24 months |
| Progression-free survival in B NHL | Up to 24 months |
| OS in B NHL | Up to 24 months |
| Incidence of CD19-negative relapse at any time in B NHL | Up to 24 months |
Countries
Spain, United Kingdom, United States
Contacts
CONTACTAutolus Ltd
Outcome results
None listed