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A Study of CD19 Targeted CAR T Cell Therapy in Pediatric Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B-cell Non-Hodgkin Lymphoma (B NHL)

Phase 1
Recruiting
Conditions
Relapsed or Refractory B Cell Non-Hodgkin Lymphoma
Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia
Interventions
Registration Number
NCT06173518
Lead Sponsor
Autolus Limited
Brief Summary

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)

Detailed Description

This is a single-arm, open-label, multi-center, Phase Ib study to determine the safety and preliminary efficacy of obe-cel 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 obe-cel.

The safety and tolerability of obe-cel 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 every 6 months thereafter, and in the event any protocol defined safety stopping criteria are met. If no pre-defined safety events related to obe-cel are met, and the safety data are consistent with what has previously been observed with obe-cel, 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 obe-cel-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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
30
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
AUTO1AUTO1-
Primary Outcome Measures
NameTimeMethod
Frequency and severity of adverse events (AEs) and serious adverse events (SAEs)Up to 24 months
Incidence and duration of severe hypogammaglobulinemiaUp to 24 months
Secondary Outcome Measures
NameTimeMethod
Overall remission rate (ORR) in B ALL patientsUp to 24 months

Defined as best response of complete remission (CR) or complete remission with incomplete recovery of counts (CRi) per Investigator assessment occurring at any time after obe-cel infusion

Overall response rate (ORR) in B NHL patientsUp to 24 months

Defined as best response of complete response (CR) or partial response (PR) per Investigator assessment occurring at any time after obe-cel infusion

Detection of CAR T cells (copies/μg genomic deoxyribonucleic acid) measured by droplet digital polymerase chain reaction in the peripheral blood and BM following obe-cel infusion including duration of detectability.Up to 24 months
Quantification of depletion of circulating CD19 expressing B cells as determined by flow cytometry in the peripheral blood.Up to 24 months
Frequency and duration of hospitalization and/or critical care support to manage obe-cel-related toxicity within 6 months of obe-cel dosing.Up to 6 months
Duration of remission (DOR) in B ALLUp to 24 months
Duration of response (DOR) in B NHLUp to 24 months
Overall survival (OS) in B ALLUp to 24 months
Overall survival (OS) in B NHLUp to 24 months
Incidence of CD19-negative relapse at any time in B ALLUp to 24 months
Incidence of CD19-negative relapse at any time in B NHLUp to 24 months
Event-free survival (EFS) in B ALLUp to 24 months
Proportion of patients achieving minimal residual disease (MRD)-negative remission in bone marrow (BM) within 3 months of obe-cel dosing in B ALLUp to 24 months
Proportion of patients achieving complete remission (CR) within 3 months per Investigator assessment in B ALLUp to 24 months
Progression-free survival (PFS) in B NHLUp to 24 months
Proportion of patients undergoing stem cell transplantation (SCT) while still in CR/CRi following obe-cel (in B ALL)Up to 24 months
Proportion of enrolled patients for whom an obe-cel product can be manufactured and administered.Up to 6 months post-leukapheresis

Trial Locations

Locations (8)

Hospital Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Nino Jesus

🇪🇸

Madrid, Spain

Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Royal Manchester Children's Hospital

🇬🇧

Manchester, United Kingdom

Methodist Children's Hospital

🇺🇸

San Antonio, Texas, United States

Primary Children's Hospital

🇺🇸

Salt Lake City, Utah, United States

Great Ormond Street Hospital for Children NHS Foundation Trust

🇬🇧

London, United Kingdom

Great North Children's Hospital

🇬🇧

Newcastle Upon Tyne, United Kingdom

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