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)
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with anti-CD19 chimeric antigen receptor (CAR) T cells
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States
RECRUITINGMethodist Children's Hospital
San Antonio, Texas, United States
RECRUITINGPrimary Children's Hospital
Salt Lake City, Utah, United States
RECRUITINGHospital Vall d'Hebron
Barcelona, Spain
RECRUITINGHospital Nino Jesus
Madrid, Spain
RECRUITINGGreat Ormond Street Hospital for Children NHS Foundation Trust
London, United Kingdom
RECRUITINGRoyal Manchester Children's Hospital
Manchester, United Kingdom
RECRUITINGGreat North Children's Hospital
Newcastle upon Tyne, United Kingdom
RECRUITINGFrequency and severity of adverse events (AEs) and serious adverse events (SAEs)
Time frame: Up to 24 months
Incidence and duration of severe hypogammaglobulinemia
Time frame: Up to 24 months
Overall remission rate (ORR) in B ALL patients
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
Time frame: Up to 24 months
Overall response rate (ORR) in B NHL patients
Defined as best response of complete response (CR) or partial response (PR) per Investigator assessment occurring at any time after obe-cel infusion
Time frame: Up to 24 months
Duration of remission (DOR) in B ALL
Time frame: Up to 24 months
Duration of response (DOR) in B NHL
Time frame: Up to 24 months
Overall survival (OS) in B ALL
Time frame: Up to 24 months
Overall survival (OS) in B NHL
Time frame: Up to 24 months
Incidence of CD19-negative relapse at any time in B ALL
Time frame: Up to 24 months
Incidence of CD19-negative relapse at any time in B NHL
Time frame: Up to 24 months
Event-free survival (EFS) in B ALL
Time frame: Up 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 ALL
Time frame: Up to 24 months
Proportion of patients achieving complete remission (CR) within 3 months per Investigator assessment in B ALL
Time frame: Up to 24 months
Progression-free survival (PFS) in B NHL
Time frame: Up to 24 months
Proportion of patients undergoing stem cell transplantation (SCT) while still in CR/CRi following obe-cel (in B ALL)
Time frame: Up to 24 months
Proportion of enrolled patients for whom an obe-cel product can be manufactured and administered.
Time frame: Up to 6 months post-leukapheresis
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.
Time frame: Up to 24 months
Quantification of depletion of circulating CD19 expressing B cells as determined by flow cytometry in the peripheral blood.
Time frame: 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.
Time frame: Up to 6 months
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