Clinical trial NCT02746952: Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia
Official title: Phase I, Open Label, Dose-escalation Study Followed by a Safety Expansion Part to Evaluate the Safety, Expansion and Persistence of a Single Dose of UCART19 (Allogeneic Engineered T-cells Expressing Anti-CD19 Chimeric Antigen Receptor), Administered Intravenously in Patients With Relapsed or Refractory CD19 Positive B-cell Acute Lymphoblastic Leukaemia (B-ALL)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: B-cell Acute Lymphoblastic Leukemia
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2016-04-21
Enrollment: 25
Sex: ALL
Minimum age (years): 16
Maximum age (years): 69
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is in two parts: a dose escalation then a safety dose expansion. The purpose of the dose escalation part is to evaluate the safety and tolerability of ascending doses of UCART19 (dose-escalation part) given as a single infusion in patients with relapsed / refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL), to determine the maximum tolerated dose (MTD), the recommended dose and the lymphodepletion regimen. The purpose of the safety dose expansion is to assess the safety and tolerability of the RD for UCART19.


Eligibility criteria: Inclusion Criteria:

* Male or female participant
* Age ≥ 16 years
* Patient with relapsed or refractory CD19 positive B-acute lymphoblastic leukaemia (B-ALL) who have exhausted alternative treatment options
* Estimated life expectancy ≥ 12 weeks (according to investigator's judgement)
* Eastern Cooperative Oncology Group (ECOG) performance status \< 2

Exclusion Criteria:

* Previous treatment with gene or gene-modified cell therapy medicine products or adoptive T cell therapy
* Use of previous anti-leukemic therapy (including approved therapies and other investigational products) within 5 half-lives prior to UCART19 administration
* CD19 negative B-cell leukaemia
* Burkitt cell or mixed lineage acute leukaemia

Primary outcomes:
measure: Dose escalation part: Dose Limiting Toxicities (DLTs) occurence. Dose expansion part: AE throughout the study.
timeFrame: Dose Escalation: Up to day 28 post first UCART19 infusion. Dose Expansion: From inclusion to Month 12
Secondary outcomes:
measure: Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability
timeFrame: From inclusion to Month 12
measure: Objective Remission Rate
timeFrame: At Day 28, Day 84, Month 4, Month 6, Month 9 and Month12
measure: Duration of remission
timeFrame: From the time that response criteria are first met until the date of progression or death (whatever the reason of death), whichever occurs first, assessed up to Month 12
measure: Time to remission
timeFrame: From the date of UCART19 administration until the date that response criteria are met, assessed up to Month 12
measure: Progression Free Survival (PFS)
timeFrame: From the date of UCART19 administration until the date of progression or the date of death (whatever the reason of death), whichever occur first, assessed up to Month 12
measure: Overall Survival (OS)
timeFrame: From the date of UCART19 administration to the date of death from any cause, assessed up to Month 12
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: PARIS Cedex 12
country: France
facility: Hôpital Saint-Antoine
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Fukuoka
country: Japan
facility: Kyushyu University Hospital
city: Sapporo
country: Japan
facility: Hokkaido University Hospital
city: London
country: United Kingdom
facility: King's College Hospital NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: King's College Hospital NHS Trust
name: Reuben Benjamin, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Benjamin R, Graham C, Yallop D, Jozwik A, Mirci-Danicar OC, Lucchini G, Pinner D, Jain N, Kantarjian H, Boissel N, Maus MV, Frigault MJ, Baruchel A, Mohty M, Gianella-Borradori A, Binlich F, Balandraud S, Vitry F, Thomas E, Philippe A, Fouliard S, Dupouy S, Marchiq I, Almena-Carrasco M, Ferry N, Arnould S, Konto C, Veys P, Qasim W; UCART19 Group. Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Lancet. 2020 Dec 12;396(10266):1885-1894. doi: 10.1016/S0140-6736(20)32334-5.
citation: Benjamin R, Jain N, Maus MV, Boissel N, Graham C, Jozwik A, Yallop D, Konopleva M, Frigault MJ, Teshima T, Kato K, Boucaud F, Balandraud S, Gianella-Borradori A, Binlich F, Marchiq I, Dupouy S, Almena-Carrasco M, Pannaux M, Fouliard S, Brissot E, Mohty M; CALM Study Group. UCART19, a first-in-class allogeneic anti-CD19 chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukaemia (CALM): a phase 1, dose-escalation trial. Lancet Haematol. 2022 Nov;9(11):e833-e843. doi: 10.1016/S2352-3026(22)00245-9. Epub 2022 Oct 10.