cd19 /22 car t cells (auto3) for the treatment of b cell acute lymphoblastic leukemia (all)

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

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.

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 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 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. 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.

Keywords: acute lymphoblastic leukaemia cd19 positive cd22 positive relapsed acute lymphoblastic leukaemia refractory acute lymphoblastic leukaemia auto3