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

Relapsed or Refractory B Cell Non-Hodgkin Lymphoma Clinical Trial

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06173518
• Other study ID #: AUTO1-PY1
• Secondary ID: 2023-506307-26-0
• Status: Recruiting
• Phase: Phase 1
• Start date: November 16, 2023
• Est. completion date: November 2027

Study information

• Verified date: June 2024
• Source: Autolus Limited
• Contact: Autolus Ltd
• Phone: +44 (0) 203 911 4385
• Email: clinicaltrials[@]autolus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 CD19 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)

Description:

This is a single-arm, open-label, multi-center, Phase Ib study to determine the safety and preliminary efficacy of AUTO1 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 AUTO1.

The safety and tolerability of AUTO1 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 in the event any protocol defined safety stopping criteria are met. If no pre-defined safety events related to AUTO1 are met, and the safety data are consistent with what has previously been observed with AUTO1, 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 AUTO1-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 information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: November 2027
• Est. primary completion date: November 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 0 Years to 18 Years

Eligibility

INCLUSION CRITERIA:

• Male or female patients < 18 years old at screening

• Patients with = 6 kg body weight at screening

B ALL Cohort: r/r CD19-positive B ALL defined as:

• Primary refractory disease defined as:

1. 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.

2. COG intermediate risk cytogenetics with MRD = 1% EOI as assessed by flow cytometry.

3. COG good risk cytogenetics with = 5% disease EOI as assessed by flow cytometry

4. Down syndrome with MRD = 0.01% EOC as assessed by flow cytometry.

5. High risk infant ALL (MRD-positive disease as assessed by flow cytometry post induction and blinatumomab)

• Children's Oncology Group (COG) very high risk first relapse if first remission =18 months.

• Relapsed or refractory disease after two or more lines of systemic therapy.

• Relapsed or refractory disease after allogeneic transplant provided AUTO1 infusion occurs =3 months after stem cell transplant..

• 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

B NHL Cohort: r/r CD19-positive aggressive mature B NHL defined as:

• Relapsed after one or more prior therapies (can include allogeneic and autologous hematopoietic stem cell transplant)

• 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

• Adequate renal, hepatic, pulmonary, and cardiac function

EXCLUSION CRITERIA:

• Diagnosis of chronic myelogenous leukemia lymphoid in blast crisis

• History or presence of clinically relevant central nervous system (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

• Patients who had prior (< 3 months before AUTO 1 infusion) stem cell transplant

• Prior CD19 targeted therapy other than blinatumomab

• Patients who have experienced = Grade 3 neurotoxicity following blinatumomab

Related Conditions & MeSH terms

• Aggression
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia
• Relapsed or Refractory B Cell Non-Hodgkin Lymphoma

Intervention

Biological:
• AUTO1
Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with anti-CD19 chimeric antigen receptor (CAR) T cells

Locations

Country	Name	City	State
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Nino Jesus	Madrid
United Kingdom	Great Ormond Street Hospital for Children NHS Foundation Trust	London
United Kingdom	Great North Children's Hospital	Newcastle Upon Tyne
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Methodist Children's Hospital	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Autolus Limited

Countries where clinical trial is conducted

United States,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of adverse events (AE) and serious adverse events (SAE)		Up to 24 months
Primary	Incidence of severe hypogammaglobulinemia		Up to 24 months
Primary	Duration of severe hypogammaglobulinemia		Up to 24 months
Secondary	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 AUTO1 infusion	Up to 24 months
Secondary	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 AUTO1 infusion	Up to 24 months
Secondary	Duration of remission (DOR) in B ALL		Up to 24 months
Secondary	Duration of response (DOR) in B NHL		Up to 24 months
Secondary	Overall survival (OS) in B ALL		Up to 24 months
Secondary	Overall survival (OS) in B NHL		Up to 24 months
Secondary	Incidence of CD19-negative relapse at any time in B ALL		Up to 24 months
Secondary	Incidence of CD19-negative relapse at any time in B NHL		Up to 24 months
Secondary	Event-free survival (EFS) in B ALL		Up to 24 months
Secondary	Proportion of patients achieving minimal residual disease (MRD)-negative remission in bone marrow (BM) within 3 months of AUTO1 dosing in B ALL		Up to 24 months
Secondary	Proportion of patients achieving complete remission (CR) within 3 months per Investigator assessment in B ALL		Up to 24 months
Secondary	Progression-free survival (PFS) in B NHL		Up to 24 months