Clinical trial NCT03190278: Study Evaluating Safety and Efficacy of UCART123v1.2 in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Official title: Phase I, Open Label Dose Escalation and Dose-Expansion Study to Evaluate the Safety, Expansion, Persistence, and Clinical Activity of UCART123 (Allogeneic Engineered T-cells Expressing Anti-CD123 Chimeric Antigen Receptor), Administered in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Relapsed/Refractory Acute Myeloid Leukemia
Keywords: Acute Myeloid Leukemia
Relapsed/Refractory Acute Myeloid Leukemia
Chimeric Antigen Receptor T-Cell (CAR-T) therapy
Allogeneic
Transcription Activator-Like Effector Nuclease (TALEN)
Lead sponsor: Cellectis S.A.
Sponsor class: INDUSTRY
First posted: 2017-06-16
Enrollment: 65
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Phase I, open-label, dose-escalation and dose-expansion study evaluating the safety and efficacy of Universal Chimeric Antigen Receptor T-cell (UCART) targeting the Cluster of Differentiation 123 (CD123) in patients with relapsed/refractory acute myeloid leukemia (AML). The purpose of this study is to evaluate the safety and clinical activity of Universal Chimeric Antigen Receptor T-cells targeting CD123 (UCART123v1.2) and determine the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D).


Eligibility criteria: Main Inclusion Criteria:

* Patients with relapsed or primary refractory AML (as defined in World Health Organization \[WHO\] criteria) with ≥5% bone marrow blasts
* Patients with CD123+ blast cells (verified by flow cytometry)
* Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of ≤1
* Adequate organ function, including bone marrow, renal, hepatic, pulmonary, and cardiac function based on the last assessment performed within screening period
* (Dose-escalation) Identified donor and transplant strategy prior to lymphodepletion (LD)
* Other criteria may apply

Main Exclusion Criteria:

* Patients with acute promyelocytic leukemia (APL) or central nervous system (CNS) Leukemia
* Previous investigation gene or cell therapy (including CAR)
* \> 1 prior allogeneic stem cell transplantations (SCTs)
* Prior treatment with rituximab or other anti-cluster of differentiation 20 (anti-CD20) therapy within 3 months
* Any known active or uncontrolled infection
* Other criteria may apply

Primary outcomes:
measure: Incidence of adverse events (AE)/serious adverse events (SAE)/Dose Limiting Toxicities (DLT) [Safety and Tolerability]
timeFrame: 24 Months
measure: Dose escalation and expansion part: Occurrence of DLTs
timeFrame: Up to Day 28 post last UCART123v1.2 infusion
Secondary outcomes:
measure: Investigators assessed overall response rate according to the European Leukemia Net (ELN) Response Criteria
timeFrame: At Day 28, Day 56, Day 84, Month 3, Month 6, Month 9, Month 12, Month 15, Month 18, Month 21 and Month 24
measure: Duration of Response
timeFrame: From the date of the initial response to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24
measure: Progression Free Survival
timeFrame: From the first day of study treatment to the date of disease progression or death from any cause, whichever occurs first, assessed up to Month 24
measure: Overall Survival
timeFrame: From the first day of study treatment to the date of death from any cause, assessed up to Month 24
measure: Pharmacokinetic (PK) Analysis: Standard PK Analysis will be completed to obtain Maximum plasma concentration (Cmax)
timeFrame: alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
measure: Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain time to reach Cmax (Tmax)
timeFrame: alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
measure: Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain total area under curve from zero to infinity (AUC-infinity)
timeFrame: alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
measure: Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Rate
timeFrame: alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
measure: Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Terminal Half-life
timeFrame: alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
measure: Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Clearance
timeFrame: alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
measure: Pharmacokinetic Analysis: Standard PK Analysis will be completed to obtain Volume of Distribution
timeFrame: alemtuzumab levels will be determined pre- and post-dose alemtuzumab and up to 48 hours after the last dose
measure: Pharmacodynamic Analysis: Pharmacodynamics Monitoring of the incidence of anti-cluster of differentiation 52 (anti-CD52; alemtuzumab) antibodies (ADA) in serum Pre-alemtuzumab administration and through Day 84
timeFrame: From screening through Day 84
measure: Pharmacodynamic Analysis: Pharmacodynamics Quantitation of T cells in peripheral blood
timeFrame: From screening through Day 84
measure: Pharmacodynamic Analysis: Pharmacodynamics Quantitation of B cells in peripheral blood
timeFrame: From screening through Day 84
measure: Pharmacodynamic Analysis: Pharmacodynamics Quantitation of natural killer (NK) cells in peripheral blood
timeFrame: From screening through Day 84
measure: Pharmacodynamic Analysis: Pharmacodynamics Quantitation of total lymphocytes in peripheral blood
timeFrame: From screening through Day 84
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco (UCSF) - Helen Diller Family Comprehensive Cancer Center
state: California
city: Miami
country: United States
facility: Sylvester Comprehensive Cancer Center
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania - Abramson Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Weill Medical College of Cornell University
name: Gail Roboz, Dr
role: PRINCIPAL_INVESTIGATOR
References: