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

This study is currently recruiting participants.
Verified September 2017 by Autolus Limited
Sponsor:
ClinicalTrials.gov Identifier:
NCT03289455
First Posted: September 21, 2017
Last Update Posted: November 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Autolus Limited
  Purpose
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.

Condition Intervention Phase
B Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Refractory Childhood Acute Lymphoblastic Leukemia B-cell Acute Lymphoblastic Leukemia Biological: AUTO3 (CD19/22 CAR T cells Phase 1 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single-Arm, Open-Label, Multi-Centre, Phase I/II Study Evaluating the Safety and Clinical Activity Of AUTO3, a CAR T Cell Treatment Targeting CD19 And CD22 in Paediatric And Young Adult Patients With Relapsed or Refractory B Cell Acute Lymphoblastic Leukaemia

Resource links provided by NLM:


Further study details as provided by Autolus Limited:

Primary Outcome Measures:
  • Phase I - safety (incidence of Grade 3-5 toxicities) and confirmation of Phase II dose and schedule. [ Time Frame: Within 30 days post AUTO-2 infusion. ]
  • Phase II - complete remission rate minimal residual disease (MRD) negative response. [ Time Frame: Within 30 days ]

Secondary Outcome Measures:
  • Feasibility of generating AUTO3: number of patients' cells successfully manufactured as a proportion of the number of patients undergoing leukapheresis [ Time Frame: Up to 8 weeks post leukapheresis ]
  • Disease Free Survival (DFS) [ Time Frame: Up to 2 years ]
  • Progression-Free Survival (PFS) [ Time Frame: Up to 2 years ]
  • Overall Survival (OS) [ Time Frame: Up to 2 years ]

Estimated Enrollment: 50
Actual Study Start Date: June 26, 2017
Estimated Study Completion Date: December 2021
Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AUTO3
Paediatric patients with relapse or refractory B-cell ALL
Biological: AUTO3 (CD19/22 CAR T cells
Following preconditioning with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with 1 to 2.0 x 10⁶/kg CD19/CD22 Chimeric Antigen Receptor (CAR) positive T cells as a single or split dose.

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.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

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

    1. Any 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 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.

For AUTO3 Infusion: Patients meeting any of the following exclusion criteria will not be treated with AUTO3 or treatment will be delayed until they no longer meet these criteria:

  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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03289455


Contacts
Contact: Autolus Limited +44 (0)2038296230 contact@autolus.com

Locations
United Kingdom
Great Ormond Street Hospital for Children NHS Foundation Trust Recruiting
London, United Kingdom
Principal Investigator: Professor Persis Amrolia         
University College London Hospitals NHS Foundation Trust Recruiting
London, United Kingdom
Principal Investigator: Dr Rachael Hough         
Royal Manchester Children's Hospital Recruiting
Manchester, United Kingdom
Principal Investigator: Professor Robert Wynn         
Sponsors and Collaborators
Autolus Limited
  More Information

Responsible Party: Autolus Limited
ClinicalTrials.gov Identifier: NCT03289455     History of Changes
Other Study ID Numbers: AUTO3-PA1
2016-004680-39 ( EudraCT Number )
First Submitted: September 11, 2017
First Posted: September 21, 2017
Last Update Posted: November 2, 2017
Last Verified: September 2017

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Autolus Limited:
Acute Lymphoblastic Leukaemia
CD19 Positive
CD22 Positive
Relapsed Acute Lymphoblastic Leukaemia
Refractory Acute Lymphoblastic Leukaemia
AUTO3

Additional relevant MeSH terms:
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Burkitt Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma