Phase 2
N=15
CD19 /22 CAR T Cells (AUTO3) for the Treatment of B Cell Acute Lymphoblastic Leukemia (ALL)
B Acute Lymphoblastic Leukemia · Recurrent Childhood Acute Lymphoblastic Leukemia · Refractory Childhood Acute Lymphoblastic Leukemia · B-cell Acute Lymphoblastic Leukemia
Bottom Line
View on ClinicalTrials.gov: NCT03289455 ↗Enrolled (actual)
15
Serious AEs
40.0%
Results posted
Feb 2021
Primary outcome: Primary: Number of Patients With Grade 3-5 Toxicities Occurring Within the Dose Limiting Toxicity (DLT) Period of AUTO3 Infusion — 4; 4; 6 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- AUTO3 (CD19/22 CAR T cells (Biological)
- Age
- Pediatric, Adult · 1+ yrs
- Sex
- All
- Sponsor
- Autolus Limited
- Primary completion
- May 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Grade 3-5 Toxicities Occurring Within the Dose Limiting Toxicity (DLT) Period of AUTO3 Infusion |
4; 4; 6 | — |
| PRIMARY Number of Patients With Dose Limiting Toxicity (DLT) of AUTO3 |
0; 0; 0 | — |
| PRIMARY 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)). |
3; 5; 5 | — |
| SECONDARY Feasibility of Generating AUTO3: Number of Patients' Cells Successfully Manufactured as a Proportion of the Number of Patients Undergoing Leukapheresis |
19 | — |
| SECONDARY Event-Free Survival (EFS) by Morphological Analysis |
3.48; 12.42; 2.79 | — |
| SECONDARY Number of Patients With CD19- and/or CD22-negative Relapse |
0; 2; 1 | — |
| SECONDARY Relapse-Free Survival (RFS) by Morphological Analysis |
6.09; 11.50; 3.98 | — |
| SECONDARY Overall Survival (OS) |
10.17; 25.20; NA | — |
| SECONDARY Expansion of AUTO3 Following Adoptive Transfer |
10240; 102000; 79800 | — |
| SECONDARY Persistence of AUTO3 Following Adoptive Transfer |
41.7; 343.7; 24.3 | — |
| SECONDARY Duration of B Cell Aplasia |
NA; NA; NA | — |
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.
Eligibility Criteria
Key Inclusion Criteria
- 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 72 hours prior to AUTO3 infusion and leukapheresis. However, physiological replacement doses of steroids are allowed: 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.
Data sourced from ClinicalTrials.gov (NCT03289455). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.