Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia (CALM)

• ClinicalTrials.gov Identifier: NCT02746952
• Recruitment Status: Completed
• First Posted: April 21, 2016
• Last Update Posted: December 24, 2020
• Sponsor: Institut de Recherches Internationales Servier
• Collaborator: ADIR, a Servier Group company
• Information provided by (Responsible Party): Servier ( Institut de Recherches Internationales Servier )

Tracking Information

• First Submitted Date: March 7, 2016
• First Posted Date: April 21, 2016
• Last Update Posted Date: December 24, 2020
• Actual Study Start Date: August 1, 2016
• Actual Primary Completion Date: July 28, 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 23, 2019): Dose escalation part: Dose Limiting Toxicities (DLTs) occurence. Dose expansion part: AE throughout the study. [ Time Frame: Dose Escalation: Up to day 28 post first UCART19 infusion. Dose Expansion: From inclusion to Month 12 ]

Original Primary Outcome Measures (submitted: April 18, 2016)

Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: through study completion, an average of 12 weeks ]

Adverse events assessed according to NCI-CTCAE v4.0 criteria

Current Secondary Outcome Measures (submitted: October 23, 2019)

• Incidence and Severity of Adverse Events as a Measure of Safety and Tolerability [ Time Frame: From inclusion to Month 12 ]
  Adverse events assessed according to NCI-CTCAE v5.0 criteria
• Objective Remission Rate [ Time Frame: At Day 28, Day 84, Month 4, Month 6, Month 9 and Month12 ]
  Proportion of patients in whom a response among molecular complete remission (mCR), morphologic complete remission (CR) and complete remission with incomplete blood count recovery (CRi)
• Duration of remission [ Time Frame: 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 [ Time Frame: From the date of UCART19 administration until the date that response criteria are met, assessed up to Month 12 ]
• Progression Free Survival (PFS) [ Time Frame: 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 ]
• Overall Survival (OS) [ Time Frame: From the date of UCART19 administration to the date of death from any cause, assessed up to Month 12 ]

Original Secondary Outcome Measures (submitted: April 18, 2016)

• Anti-leukemic activity of UCART19 [ Time Frame: At day 28 ]
  The biological active dose will be the dose leading to, at least, 66% patients with objective responses in the cohort, either in ALL or CLL patients or both, at Day 28. For ALL: an objective response is defined as: (1) a morphologic complete response (CR) or (2) a complete response with incomplete recovery of counts (CRi) (based on NCCN guidelines (National Comprehensive Cancer Network (NCCN), 2014) or (3) a negative minimal residual disease (MRD < 10^-4 post treatment). For CLL: an objective response is defined as: (1) a complete response or (2) a partial response (based on CLL guidelines, (Hallek, 2008)).
• Minimal Residual Disease (MRD) evaluation [ Time Frame: At day 28 ]
  Assessed by multiparametric flow cytometry or qPCR
• Disease-free survival [ Time Frame: At day 84 ]
• Overall survival [ Time Frame: At day 84 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: B-cell Acute Lymphoblastic Leukemia

Intervention

Biological: UCART19

Other Name: S68587

Study Arms

Experimental: UCART19

Intervention: Biological: UCART19

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 15, 2020): 25
• Original Estimated Enrollment (submitted: April 18, 2016): 12
• Actual Study Completion Date: July 28, 2020
• Actual Primary Completion Date: July 28, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years to 69 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Japan, United Kingdom, United States

Administrative Information

• NCT Number: NCT02746952
• Other Study ID Numbers: CL1-68587-002; 2016-000296-24 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

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.

• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (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.
• URL: https://clinicaltrials.servier.com/

• Responsible Party: Servier ( Institut de Recherches Internationales Servier )
• Study Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company

Investigators

• Principal Investigator: Reuben Benjamin, MD, PhD; King's College Hospital NHS Trust

• PRS Account: Servier
• Verification Date: December 2020