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

NCT ID: NCT03289455

Last Updated: 2021-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-26
• Study Completion Date: 2020-05-18

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.

Detailed Description

The study will consist of 2 phases, a Phase I or dose escalation phase and a Phase II or expansion phase. Paediatric or young adult patients with relapsed or refractory B cell ALL will be enrolled in both phases of the study. Eligible patients will undergo leukapheresis in order to harvest T cells, which is the starting material for the manufacture of the autologous CAR T product AUTO3 which is a CD19 and CD22 dual targeting CAR T cell product. Following pre-conditioning by a chemotherapeutic regimen, the patient will receive AUTO3 intravenously as a single or split dose and will then enter a 24-month follow-up period.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AUTO3

Paediatric patients with relapse or refractory B-cell ALL

Group Type: EXPERIMENTAL

AUTO3 (CD19/22 CAR T cells

Intervention Type: 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.

Interventions

AUTO3 (CD19/22 CAR T cells

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male or female patients aged 1-24 years with high risk (HR) relapsed/refractory B-lineage ALL, AND:

1. 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,

2. HR first relapse; OR,

3. Standard risk relapse patients with HR cytogenetics; OR,

4. Second or greater relapse; OR,

5. BM minimal residual disease (MRD) ≥10-³ prior to planned SCT; OR,

6. Any on-treatment relapse in patients aged 16-24 years.

(Phase II Only - Criteria in addition to those described above:)

7. Primary refractory disease; OR,

8. 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,

9. Isolated CNS relapse but with ≤CNS Grade 2 disease at time of enrolment.

2. Documentation of CD19 and or CD22 expression on leukaemic blasts in the BM, peripheral blood, or cerebrospinal fluid within 3 months of screening.

3. Detectable disease in the BM at a level ≥10-⁴ (Phase I only).

4. Absolute lymphocyte count ≥0.5 x 10⁹/L.

5. Adequate renal, hepatic, pulmonary, and cardiac function.

6. Karnofsky (age ≥10 years) or Lansky (age <10 years) score ≥50%.

7. Willing and able to give written, informed consent to the current study (patient and/or parent or legal guardian).

Exclusion Criteria

1. Isolated extra-medullary disease relapse.

2. Active CNS involvement of ALL (CNS Grade 3 per National Comprehensive Cancer Network guidelines).

3. Active infectious bacterial or viral disease requiring IV anti-microbials for treatment.

4. Females who are pregnant or lactating.

5. 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.

6. Inability to tolerate leukapheresis.

7. 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.

8. Pre-existing significant neurological disorder.

9. 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.

10. The following medications are excluded:

1. 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.

2. Allogeneic cellular therapy: Any donor lymphocyte infusions must be completed >6 weeks prior to AUTO3 infusion.

3. Graft versus host disease therapies: Any drug used for GVHD must be stopped >4 weeks prior to AUTO3 infusion.

4. Chemotherapy: Should be stopped 1 week prior to leukapheresis and 2 days prior to starting pre-conditioning chemotherapy.

11. Known allergy to albumin, dimethyl sulfoxide, cyclophosphamide or fludarabine.

1. Severe intercurrent infection.

2. Requirement for supplementary oxygen.

3. Allogeneic transplant recipients with active significant acute GVHD overall Grade ≥II or moderate/severe chronic GVHD requiring systemic steroids.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 24 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Autolus Limited

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Great Ormond Street Hospital for Children NHS Foundation Trust

London, , United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Royal Manchester Children's Hospital

Manchester, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36821767 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004680-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AUTO3-PA1

Identifier Type: -

Identifier Source: org_study_id