A Single-Arm, Open-Label, Multicenter, Phase 1b/2 Study Evaluating the Safety and Efficacy of AUTO1 (obecabtagene autoleucel [obe-cel]) in Pediatric Patients with CD19-positive Relapsed/Refractory (R/R) B cell Acute Lymphoblastic Leukemia (B ALL) or R/R Aggressive Mature B Cell Non–Hodgkin Lymphoma (B NHL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Autolus Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 May 2024 → ongoing

Decision date (initial)

2023-09-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Autolus Limited

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

B ALL Cohort: To demonstrate the clinical efficacy of obe-cel treatment regimen in pediatric participants with r/r B ALL.
B ALL and B NHL Cohorts: To evaluate the safety and tolerability of obe-cel in pediatric participants with B ALL and B NHL.

Secondary objectives 5

1. B ALL Cohort: To demonstrate the clinical efficacy of obe-cel treatment regimen in achieving minimal residual disease (MRD) remission in pediatric participants with r/r B ALL
2. B ALL and B NHL Cohorts: To evaluate the expansion and persistency of obe-cel
3. B ALL and B NHL Cohorts: To evaluate the duration of B cell aplasia
4. B ALL and B NHL Cohorts: To evaluate the health care resource utilization for the management of obe-cel-related toxicity
5. B ALL Cohort: To evaluate the preliminary clinical efficacy of obe-cel in pediatric participants with r/r B ALL

Conditions and MedDRA coding

B-cell Acute Lymphoblastic Leukemia (B ALL) and Aggressive Mature B-cell Non-Hodgkin Lymphoma (B NHL).

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-003171-PIP01-21

Plan to share IPD

No

IPD plan description

N/A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Males or females < 18 years old at screening
2. ≥ 6 kg body weight at screening
3. Willing and able to give written, informed consent to the current study (participant and/or parent or legal guardian).
4. Agreement to have a pregnancy test and use adequate contraception (if applicable).
5. Participants with a diagnosis of r/r CD19-positive B ALL defined as one of the following sub-categories: (1) Primary refractory (2) First relapse (3) Second or greater relapse (4) Relapsed or refractory disease post-allogeneic stem cell transplant (5) Philadelphia chromosome-positive (Ph+) ALL. All B ALL participants enrolled during the Phase 2 portion of the study must meet a disease status, documented at screening per NCCN Guidelines: Pediatric ALL definitions for r/r pediatric B ALL
6. Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) performance score ≥ 50.
7. For individuals with B ALL, documentation of CD19 expression on leukemic blasts in the BM, peripheral blood or cerebrospinal fluid (CSF), or biopsy no more than 30 days prior to consent. In participants treated with blinatumomab, testing should be undertaken after blinatumomab therapy has been stopped. In participants with mature B NHL, CD19 expression must be confirmed in a biopsy after any CD19-targeting therapies.

Exclusion criteria 8

1. Chronic myelogenous leukemia lymphoid in blast crisis.
2. History or presence of clinically relevant CNS pathology
3. Active CNS involvement by malignancy, defined as CNS-3 per pediatric NCCN Guidelines. Note: Individuals with a history of CNS disease that has been effectively treated to CNS1 or CNS2 status at the time of enrollment will be eligible
4. Presence of active or uncontrolled fungal, bacterial, viral, or other infection requiring systemic antimicrobials for management.
5. History or presence of active or latent Hepatitis B virus or active Hepatitis C virus.
6. History of human immunodeficiency virus (HIV), human T cell lymphotropic virus (HTLV)-1, HTLV-2, or syphilis positive test.
7. Prior CD19 targeted therapy other than blinatumomab.
8. Patients who have experienced ≥ Grade 3 neurotoxicity following blinatumomab.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. B ALL Cohort: Proportion of pediatric participants with r/r B ALL at screening who achieve CR within 3 months of obe-cel infusion per IRRC assessment
2. B ALL Cohort: Proportion of pediatric participants with r/r B ALL at screening who achieve ORR (CR + CRi) within 3 months of obe-cel infusion per IRRC assessment
3. B ALL and B NHL Cohorts: Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) after receiving obe-cel infusion
4. B ALL and B NHL Cohorts: Incidence and duration of severe hypogammaglobulinemia

Secondary endpoints 3

1. B-ALL Cohort (Key Secondary): Proportion of pediatric participants with r/r B ALL with successful ClonoSEQ® NGS MRD calibration who achieve MRD-negative ORR below the 10-4 level (< 0.01%) within 3 months of obe-cel infusion per IRRC assessment
2. B-NHL Cohort (Secondary): • ORR (CR + PR) • Duration of response (DoR); • Progression free survival (PFS); • Overall survival (OS); • Incidence of CD19-negative relapse.
3. B ALL Cohort (Secondary): • CR at any time • ORR (CR + CRi) at any time • MRD-negative ORR below the 10-4 level (< 0.01%) at any time • Duration of Remission (DoR) • Event Free Survival (EFS) • Overall Survival (OS) • Proportion of participants undergoing HSCT while still in CR/CRi following obe-cel • Incidence of CD19-negative relapse at any time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Autolus Limited

Sponsor organisation

Autolus Limited

Address

191 Wood Lane

City

London

Postcode

W12 7FP

Country

United Kingdom

Scientific contact point

Organisation

Autolus Limited

Contact name

Ram Malladi

Public contact point

Organisation

Autolus Limited

Contact name

Ram Malladi

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

10 submissions — initial application plus substantial / non-substantial modifications