RECRUITING

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)

Conditions

Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia Relapsed or Refractory B Cell Non-Hodgkin Lymphoma 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 AUTO1 Obecabtagene autoleucel CD19-positive CAR T cell Obe-cel

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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)

Official Title

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)

Quick Facts

Study Start:2023-11-16

Study Completion:2027-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06173518

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:0 Years to 18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Male or female patients \< 18 years old at screening * Patients with ≥ 6 kg body weight at screening 1. Primary refractory disease defined as: 1. National Cancer Institute high risk (defined as presenting with white blood cell count ≥ 50 × 10\^9 cells/L or aged ≥ 10 years at diagnosis) patients with MRD ≥ 0.01% after first-line induction and consolidation and blinatumomab (if allowed per country specific approvals and treatment guidelines). 2. Refractory B ALL if BM disease ≥ 25% after first line induction and consolidation. 3. KMT2A rearranged infant ALL with MRD ≥ 1% after first line induction and blinatumomab (if allowed per country specific approvals and treatment guidelines) or MRD ≥ 0.01% after first line induction and consolidation. 2. First relapse 1. Children's Oncology Group high risk first relapse involving BM \< 36 months after initial diagnosis or an isolated extramedullary relapse \< 18 months after initial diagnosis. 2. Patients with Down syndrome and infants with KMT2A rearranged are eligible with first relapse at any time. 3. Refractory disease with MRD ≥ 0.01% after re-induction for first relapse (with or without blinatumomab, if allowed per country specific approvals and treatment guidelines). 3. Second or greater relapse 4. Relapsed or refractory post-SCT: 5. Philadelphia chromosome positive (Ph+) ALL: 1. Any of the above with Ph+ ALL where patient is intolerant to or has failed at least one tyrosine kinase inhibitor (TKI) or if TKI therapy is contraindicated. 1. Relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic SCT). 2. 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. 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. * Adequate renal, hepatic, pulmonary, and cardiac function.	* Diagnosis of chronic myelogenous leukemia lymphoid in blast crisis. * History or presence of clinically relevant central nervous system (CNS) pathology unrelated to CNS leukemia. * 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 obe-cel infusion) stem cell transplant. * Prior CD19 targeted therapy other than blinatumomab. * Patients who have experienced Grade ≥ 3 neurotoxicity following blinatumomab.

Inclusion Criteria

Exclusion Criteria

* Male or female patients \< 18 years old at screening
* Patients with ≥ 6 kg body weight at screening
1. Primary refractory disease defined as:
1. National Cancer Institute high risk (defined as presenting with white blood cell count ≥ 50 × 10\^9 cells/L or aged ≥ 10 years at diagnosis) patients with MRD ≥ 0.01% after first-line induction and consolidation and blinatumomab (if allowed per country specific approvals and treatment guidelines).
2. Refractory B ALL if BM disease ≥ 25% after first line induction and consolidation.
3. KMT2A rearranged infant ALL with MRD ≥ 1% after first line induction and blinatumomab (if allowed per country specific approvals and treatment guidelines) or MRD ≥ 0.01% after first line induction and consolidation.
2. First relapse
1. Children's Oncology Group high risk first relapse involving BM \< 36 months after initial diagnosis or an isolated extramedullary relapse \< 18 months after initial diagnosis.
2. Patients with Down syndrome and infants with KMT2A rearranged are eligible with first relapse at any time.
3. Refractory disease with MRD ≥ 0.01% after re-induction for first relapse (with or without blinatumomab, if allowed per country specific approvals and treatment guidelines).
3. Second or greater relapse
4. Relapsed or refractory post-SCT:
5. Philadelphia chromosome positive (Ph+) ALL:
1. Any of the above with Ph+ ALL where patient is intolerant to or has failed at least one tyrosine kinase inhibitor (TKI) or if TKI therapy is contraindicated.
1. Relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic SCT).
2. 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. 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.
* Adequate renal, hepatic, pulmonary, and cardiac function.

* Diagnosis of chronic myelogenous leukemia lymphoid in blast crisis.
* History or presence of clinically relevant central nervous system (CNS) pathology unrelated to CNS leukemia.
* 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 obe-cel infusion) stem cell transplant.
* Prior CD19 targeted therapy other than blinatumomab.
* Patients who have experienced Grade ≥ 3 neurotoxicity following blinatumomab.

Contacts and Locations

Study Contact

Autolus Ltd

CONTACT

+44 (0) 203 911 4385

clinicaltrials@autolus.com

Study Locations (Sites)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

Methodist Children's Hospital

San Antonio, Texas, 78229

United States

Primary Children's Hospital

Salt Lake City, Utah, 84113

United States

Collaborators and Investigators

Sponsor: Autolus Limited

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-11-16

Study Completion Date2027-11

Study Record Updates

Study Start Date2023-11-16

Study Completion Date2027-11

Terms related to this study

Keywords Provided by Researchers

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
AUTO1
Obecabtagene autoleucel
CD19-positive CAR T cell
Obe-cel

Additional Relevant MeSH Terms

Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia
Relapsed or Refractory B Cell Non-Hodgkin Lymphoma