Adverse genetic Acute Myeloid Leukaemia MedDRA version: 20.0 Level: LLT Classification code 10000878 Term: Acute myeloblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: UCART123
Pharmaceutical Form: Infusion
INN or Proposed INN: CD123-CAR+_TCRaß–_T-cells
Other descriptive name: UCART123
Con
Sponsors
CELLECTIS SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Aged between 18 and 65 years; 2. Weight =42 kg; 3. Patients newly diagnosed with CD123 positive adverse genetic risk acute myeloid leukaemia (AML), including patients with CD123 positive AML secondary to MDS, who do not achieve complete remission, and whose bone marrow blast content is 50% as assessed by echocardiography; and v. Must have a minimum level of pulmonary reserve defined as Grade =65 years) yes F.1.3.1 Number of subjects for this age range 3
Exclusion criteria
Exclusion criteria: 1. Patients with =20% blasts in bone marrow after 1 or 2 courses of standard intensive induction chemotherapy; 2. Patients with AML transformed from previously diagnosed myeloproliferative disorder; 3. Patients with APL; 4. Evidence of uncontrolled CNS leukaemia or evidence of CNS leukaemia on CSF examination; 5. AML relapsing after first complete remission; 6. Prior allogeneic stem cell transplant; 7. Therapy-related AML; 8. Favourable or intermediate risk AML; 9. Prior gene or experimental cellular therapy; 10. Active uncontrolled infection or organ dysfunction that in the opinion of the investigator precludes intensive induction chemotherapy or cellular therapy; 11. Use of other investigational products within five half-lives or within 14 days prior to start of lymphodepletion, whichever is longer; participation in non-interventional registries or epidemiological studies is allowed. In addition, treatment-related toxicities should have resolved to no more than Grade 1; 12. Use of rituximab and other anti-CD20 antibodies known to have the same epitope as rituximab or anti-CD20 antibodies for which the epitope is unknown within 3 months or 5 half-lives prior to enrolment, whichever is longer. Any contraindication to or safety concern preventing the potential use of rituximab; 13. Patients may not receive = 20 mg of prednisone or equivalent between Day -7 and Day 28 of UCART123 administration. Hydrocortisone required for mineralocorticoid replacement therapy is authorized at all times as needed clinically. Topical, inhaled, or nasal route of steroids are permitted; 14. Known infection with human immunodeficiency virus or human T-cell leukaemia/lymphoma virus type 1; 15. A known hypersensitivity to any of the test materials or related compounds including murine and bovine products; 16. Any planned medical/surgical treatment that might interfere with the ability to comply with the study requirements; or 17. Evidence of another uncontrolled malignancy within 2 years prior to Screening (except in situ non-melanoma skin cell cancers and in situ cervical carcinoma).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the safety and tolerability of a multiple infusion schedule of UCART123 in patients with CD123+ adverse genetic risk AML who do not achieve morphologic or cytogenetic complete remission after induction chemotherapy. 2. To determine the Maximum Tolerated Dose (MTD) of UCART123. ; Secondary Objective: To assess the efficacy and tolerability of UCART123 in patients with CD123+ adverse genetic risk AML who do not achieve morphologic or cytogenetic complete remission after induction chemotherapy, by measuring: • Rate and severity of cytokine release syndrome, • Rate and severity of UCART123 related adverse events, • Rate of morphological CR at Day 28 after each UCART123 infusion, • Rate of cytogenetic CR at Day 28 after each UCART123 infusion, • Rate of CR without MRD at Day 28 after each UCART123 infusion, and • Leukaemia-free survival (LFS) and overall survival (OS). ; Primary end point(s): -Safety Endpoint • Evaluation of DLT, Incidence, nature, and severity of adverse events and serious adverse events (SAEs) throughout the study (CTCAE v4.03; Lee et al., 2014 for CRS; Cairo and Bishop 2004 for TLS, New consensus criteria 2016 for GvHD). ; Timepoint(s) of evaluation of this end point: • DLT at Day 28 post first UCART123 infusion and adverse events are assessed throughout the study | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Efficacy Endpoints • Antileukemic activity, as measured by European Leukaemia Net (ELN) Response Criteria in AML (Döhner et al., 2017). ; Timepoint(s) of evaluation of this end point: • Antileukemic Response will be assessed following each UCART123 administration at Day 14 and Day 28, at EOT visit and as clinically relevant | — |
Countries
United Kingdom
Contacts
Public ContactRegulatory and Compliance Affairs
CELLECTIS SA
Outcome results
None listed