CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL)

NCT03289455 | Completed Phase 1 Results DMC

• 2 other identifiers: AUTO3-PA12016-004680-39
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to test the safety and efficacy of AUTO3, a CAR T cell treatment targeting CD19 and CD22 in paediatric or young adult patients with relapsed or refractory B cell acute lymphoblastic leukaemia.

Conditions

B Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia; B-cell Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic Leukaemia; CD19 Positive; CD22 Positive; Relapsed Acute Lymphoblastic Leukaemia; Refractory Acute Lymphoblastic Leukaemia; AUTO3

Outcome Measures

Primary Outcomes (3)

• Number of Patients With Grade 3-5 Toxicities Occurring Within the Dose Limiting Toxicity (DLT) Period of AUTO3 Infusion

  Within 30 days (+/- 3 days) after the last dose of AUTO3.

• Number of Patients With Dose Limiting Toxicity (DLT) of AUTO3

  DLT was defined as i) any new non-hematological adverse event (AE) of Grade 3 or higher toxicity using the NCI CTCAE (version 5.0), which was probably or definitely related to AUTO3 therapy, which occurred within the DLT evaluation period, and which failed to resolve to Grade 2 or better within 14 days, despite appropriate supportive measures; ii) Grade 4 cytokine release syndrome (CRS) or neurotoxicity, cerebral edema, or Grade 3 neurotoxicity (including cerebral edema) that lasted \>72 hours; iii) Grade \>3 disseminated intravascular coagulation; iv) Grade \>2 infusion reaction; v) Any other fatal event (Grade 5) or life-threatening event (Grade 4) that could not be managed with conventional supportive measures or which in the opinion of the Safety Evaluation Committee (SEC) necessitated dose reduction or other modification to trial treatment to avoid a similar hazard in future patients.

  Within 30 days (+/- 3 days) after the last dose of AUTO3.

• Number of Patients Achieving Morphological Remission (Complete Response(CR) or Complete Response With Incomplete Count Recovery (CRi) and Minimal Residual Disease (MRD)-Negative Response in the Bone Marrow (PCR)).

  Morphological response evaluations were based on the response criteria for ALL according to the NCCN guidelines version 2.2014. Minimal residual disease-negative status was achieved if MRD was \<10\^-4 (0.01%) by PCR amplification of individual rearrangements of Ig genes and/or flow cytometry MRD testing.

  Within 30 days (+/- 3 days) post AUTO3 infusion

Secondary Outcomes (8)

• Feasibility of Generating AUTO3: Number of Patients' Cells Successfully Manufactured as a Proportion of the Number of Patients Undergoing Leukapheresis

  Up to 8 weeks post leukapheresis

• Event-Free Survival (EFS) by Morphological Analysis

  Up to 2 years

• Number of Patients With CD19- and/or CD22-negative Relapse

  Up to 2 years

• Relapse-Free Survival (RFS) by Morphological Analysis

  Up to 2 years

• Overall Survival (OS)

  Up to 2 years after the last patient was infused

Study Arms (1)

AUTO3

EXPERIMENTAL

Paediatric patients with relapse or refractory B-cell ALL

Biological: AUTO3 (CD19/22 CAR T cells

Interventions

AUTO3 (CD19/22 CAR T cells BIOLOGICAL

Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with 1 to 5.0 x 10⁶/kg CD19/CD22 Chimeric Antigen Receptor (CAR) positive T cells as a single or split dose.

AUTO3

Eligibility Criteria

• Age: 1 Year - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male or female patients aged 1-24 years with high risk (HR) relapsed/refractory B-lineage ALL, AND:
• Any bone marrow (BM) relapse or central nervous system (CNS) relapse with detectable BM disease after allogeneic stem cell transplant (SCT) and must be ≥6 months from SCT at the time of AUTO3 infusion; OR,
• HR first relapse; OR,
• Standard risk relapse patients with HR cytogenetics; OR,
• Second or greater relapse; OR,
• BM minimal residual disease (MRD) ≥10-³ prior to planned SCT; OR,
• Any on-treatment relapse in patients aged 16-24 years.
• (Phase II Only - Criteria in addition to those described above:)
• Primary refractory disease; OR,
• Patients with Philadelphia chromosome positive ALL are eligible if they are intolerant to or have failed 2 lines of tyrosine kinase inhibitor (TKI) therapy, or if TKI therapy is contraindicated; OR,
• Isolated CNS relapse but with ≤CNS Grade 2 disease at time of enrolment.
• Documentation of CD19 and or CD22 expression on leukaemic blasts in the BM, peripheral blood, or cerebrospinal fluid within 3 months of screening.
• Detectable disease in the BM at a level ≥10-⁴ (Phase I only).
• Absolute lymphocyte count ≥0.5 x 10⁹/L.
• Adequate renal, hepatic, pulmonary, and cardiac function.

You may not qualify if:

• Isolated extra-medullary disease relapse.
• Active CNS involvement of ALL (CNS Grade 3 per National Comprehensive Cancer Network guidelines).
• Active infectious bacterial or viral disease requiring IV anti-microbials for treatment.
• Females who are pregnant or lactating.
• Females of child-bearing potential and post pubertal male participants who are unwilling to use highly effective methods of contraception for a period of 1 year after the AUTO3 infusion.
• Inability to tolerate leukapheresis.
• Prior CD19 or CD22 targeted therapy with Grade 4 toxicity or ≥refractory Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug related CNS toxicity.
• Pre-existing significant neurological disorder.
• Stem Cell Transplant patients only: active significant acute graft versus host disease (GVHD) or moderate/severe chronic GVHD requiring systemic steroids or other immunosuppressant within 4 weeks of enrolment.
• The following medications are excluded:
• Steroids: Therapeutic doses of steroids must be stopped \>72 hours prior to AUTO3 infusion and leukapheresis. However, physiological replacement doses of steroids are allowed: \<12 mg/m2/day hydrocortisone or equivalent.
• Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed \>6 weeks prior to AUTO3 infusion.
• Graft versus host disease therapies: Any drug used for GVHD must be stopped \>4 weeks prior to AUTO3 infusion.
• Chemotherapy: Should be stopped 1 week prior to leukapheresis and 2 days prior to starting pre-conditioning chemotherapy.
• Known allergy to albumin, dimethyl sulfoxide, cyclophosphamide or fludarabine.

Sponsors & Collaborators

• Autolus Limited: lead

Study Sites (3)

Great Ormond Street Hospital for Children NHS Foundation Trust

London, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

Royal Manchester Children's Hospital

Manchester, United Kingdom

Location

Related Publications (1)

• Roddie C, Lekakis LJ, Marzolini MAV, Ramakrishnan A, Zhang Y, Hu Y, Peddareddigari VGR, Khokhar N, Chen R, Basilico S, Raymond M, Vargas FA, Duffy K, Brugger W, O'Reilly MA, Wood L, Linch DC, Peggs KS, Bachier C, Budde EL, Lee Batlevi C, Bartlett N, Irvine D, Tholouli E, Osborne W, Ardeshna KM, Pule MA. Dual targeting of CD19 and CD22 with bicistronic CAR-T cells in patients with relapsed/refractory large B-cell lymphoma. Blood. 2023 May 18;141(20):2470-2482. doi: 10.1182/blood.2022018598.

  PMID: 36821767 DERIVED

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Limitations and Caveats

Early completion of the study leading to small numbers of patients analyzed from the Phase I part of the study.

Results Point of Contact

• Title: Clinical Project Manager
• Organization: Autolus Ltd

clinicaltrials@autolus.com

+44 1483 920748

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2017
• First Posted: September 21, 2017
• Study Start: June 26, 2017
• Primary Completion: May 18, 2020
• Study Completion: May 18, 2020
• Last Updated: February 1, 2021
• Results First Posted: February 1, 2021

Record last verified: 2021-01

Locations

GB (3)