Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia
CALM
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)
2 other identifiers
interventional
25
4 countries
9
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Aug 2016
Longer than P75 for phase_1
9 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 7, 2016
CompletedFirst Posted
Study publicly available on registry
April 21, 2016
CompletedStudy Start
First participant enrolled
August 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 28, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 28, 2020
CompletedOctober 1, 2021
September 1, 2021
4 years
March 7, 2016
September 24, 2021
Conditions
Outcome Measures
Primary Outcomes (1)
Dose escalation part: Dose Limiting Toxicities (DLTs) occurence. Dose expansion part: AE throughout the study.
Dose Escalation: Up to day 28 post first UCART19 infusion. Dose Expansion: From inclusion to Month 12
Secondary Outcomes (6)
Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability
From inclusion to Month 12
Objective Remission Rate
At Day 28, Day 84, Month 4, Month 6, Month 9 and Month12
Duration of remission
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
Time to remission
From the date of UCART19 administration until the date that response criteria are met, assessed up to Month 12
Progression Free Survival (PFS)
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
- +1 more secondary outcomes
Study Arms (1)
UCART19
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (9)
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030, United States
Hôpital Saint-Louis
Paris, 75010, France
Hôpital Saint-Antoine
Paris, 75571, France
Kyushyu University Hospital
Fukuoka, 812-8582, Japan
Hokkaido University Hospital
Sapporo, 060-8648, Japan
King's College Hospital NHS Foundation Trust
London, SE5 9RS, United Kingdom
The Christie NHS Foundation Trust
Manchester, M20 4BX, United Kingdom
Related Publications (2)
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.
PMID: 33308471RESULTBenjamin 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.
PMID: 36228643DERIVED
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Reuben Benjamin, MD, PhD
King's College Hospital NHS Trust
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 7, 2016
First Posted
April 21, 2016
Study Start
August 1, 2016
Primary Completion
July 28, 2020
Study Completion
July 28, 2020
Last Updated
October 1, 2021
Record last verified: 2021-09
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- After Marketing Authorisation in EEA or US if the study is used for the approval.
- Access Criteria
- Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.