Status:
COMPLETED
CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL)
Lead Sponsor:
Autolus Limited
Conditions:
B Acute Lymphoblastic Leukemia
Recurrent Childhood Acute Lymphoblastic Leukemia
Eligibility:
All Genders
1-24 years
Phase:
PHASE1
PHASE2
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 lym...
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 ...
Eligibility Criteria
Inclusion
- Key
- 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.
- Karnofsky (age ≥10 years) or Lansky (age \<10 years) score ≥50%.
- Willing and able to give written, informed consent to the current study (patient and/or parent or legal guardian).
Exclusion
- 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.
- 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:
- Severe intercurrent infection.
- Requirement for supplementary oxygen.
- Allogeneic transplant recipients with active significant acute GVHD overall Grade ≥II or moderate/severe chronic GVHD requiring systemic steroids.
Key Trial Info
Start Date :
June 26 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 18 2020
Estimated Enrollment :
23 Patients enrolled
Trial Details
Trial ID
NCT03289455
Start Date
June 26 2017
End Date
May 18 2020
Last Update
February 1 2021
Active Locations (3)
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1
Great Ormond Street Hospital for Children NHS Foundation Trust
London, United Kingdom
2
University College London Hospitals NHS Foundation Trust
London, United Kingdom
3
Royal Manchester Children's Hospital
Manchester, United Kingdom