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Trial record 1 of 1 for:    NCT03289455
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CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell ALL (AMELIA)

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. Identifier: NCT03289455
Recruitment Status : Recruiting
First Posted : September 21, 2017
Last Update Posted : September 12, 2019
Information provided by (Responsible Party):
Autolus Limited

Tracking Information
First Submitted Date  ICMJE September 11, 2017
First Posted Date  ICMJE September 21, 2017
Last Update Posted Date September 12, 2019
Actual Study Start Date  ICMJE June 26, 2017
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 18, 2017)
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03289455 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 18, 2017)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell ALL
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • B Acute Lymphoblastic Leukemia
  • Recurrent Childhood Acute Lymphoblastic Leukemia
  • Refractory Childhood Acute Lymphoblastic Leukemia
  • B-cell Acute Lymphoblastic Leukemia
Intervention  ICMJE Biological: 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.
Study Arms  ICMJE Experimental: AUTO3
Paediatric patients with relapse or refractory B-cell ALL
Intervention: Biological: AUTO3 (CD19/22 CAR T cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 18, 2017)
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 2021
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 24 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Autolus Limited +44 (0)1483 920748
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT03289455
Other Study ID Numbers  ICMJE AUTO3-PA1
2016-004680-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Autolus Limited
Study Sponsor  ICMJE Autolus Limited
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Autolus Limited
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP