T Lymphocytes (LT) Expressing iCASP9 and ΔCD19 in Allogeneic Haematopoietic Transplantation.

NCT02849886 | Terminated Phase 1 DMC

• 1 other identifier: N/2000/39-B
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates the frequency of occurrence, severity, and response to treatment by a chemical agent, notably the dimerizer AP1903 (Bellicum Pharmaceuticals compagny), in the case of acute Graft versus Host Disease (aGvHD) occurring after the administration of T-lymphocytes expressing iCASP9 and concomitantly to a bone marrow graft depleted in B- and T-lymphocytes

Conditions

Graft Versus Host Disease; Hematological Malignancies

Keywords

GvHD; Suicide gene; Dimerizer drug AP1903; Hematological stem cell transplantation

Outcome Measures

Primary Outcomes (1)

• GvHD response to Dimerizer AP1903

  Disappearance of clinical signs of GvHD

  72 hours after administration of Dimerizer AP1903

Secondary Outcomes (5)

• Haematopoietic reconstitution (Blood)

  1 month, 3 months, 6 months, and 1 year

• Haematopoietic engraftment (bone marrow)

  1 month, 3 months, 6 months, and 1 year

• Haematopoietic engraftment (chimerism)

  1 month, 3 months, 6 months, and 1 year

• Infections post Transplantation

  1 month, 3 months, 6 months, and 1 year

• GvL effect

  1 month, 3 months, 6 months, and 1 year

Study Arms (2)

LT icasp9 ΔCD19 (cohort1)

EXPERIMENTAL

Injection T lymphocytes iCASP9 ΔCD19 (2.10e6, 5.10e6 and 10.10e6 Gene Modified Cells (GMC)/kg).

Drug: T lymphocytes iCASP9 ΔCD19

LT iCASP9 ΔCD19 & GvHD (cohort2)

EXPERIMENTAL

Injection T lymphocytes iCASP9 ΔCD19 (2.10e6, 5.10e6 and 10.10e6 GMC/kg). Patients who develop GVHD after administration of Gene Modified Cells (GMC) will be treated with dimerizer drug (AP1903)

Drug: T lymphocytes iCASP9 ΔCD19; Drug: Dimerizer drug AP1903

Interventions

T lymphocytes iCASP9 ΔCD19 DRUG

Intravenous injection of the T lymphocytes armed with the iCASP9 suicide gene

Also known as: T lymphocytes Gene Modified Cells (GMC)

LT iCASP9 ΔCD19 & GvHD (cohort2); LT icasp9 ΔCD19 (cohort1)

Dimerizer drug AP1903 DRUG

AP1903 drug will be administrated at a dose of 0.4 mg/kg by intravenous route in the two following cases: * Acute Grade ≥II or symptomatic Grade I GvHD justifying systemic immunosuppression therapy; * Grade ≥3 toxicity attributable to GMC.

Also known as: Dimerizer drug

LT iCASP9 ΔCD19 & GvHD (cohort2)

Eligibility Criteria

• Age: 40 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adult patients aged ≤55 years (40\< age ≤55 years);
• Patients who are candidates for myeloablative allogeneic bone marrow transplants: de novo or secondary acute lymphoblastic leukaemia (ALL) and acute myeloblastic leukaemia (AML) in complete remission (CR) ≥1; chronic myeloid leukaemia (CML) in chronic phase or in escape from tyrosine kinase inhibitors; myelodysplastic syndrome (MDS) with int-2 or high International Prognostic Scoring System (IPSS score, with medullary blastosis \>10%); chemosensitive malignant non-Hodgkin's lymphoma (MNHL) in CR or partial remission (PR) \>2 ; chemosensitive Hodgkin's disease in CR or PR \>2 ; chemosensitive chronic lymphoid leukaemia (CLL) in CR or PR \>2; chemosensitive myeloma in CR or PR ≥2;
• At high risk for GvHD: the risk for GvHD is considered high and the patient thus eligible for the study, if the receiver is \>40 years, or if the donor is a woman and the receiver a man, regardless their age;
• Karnofsky index \>70% or World Health Organization (WHO) index ≥2;
• Stable clinical conditions and life expectancy \>3 months;
• Absence of organic disease contraindicating the transplantation
• Availability of a genotypically identical donor, aged \>18 years, having given consent, and presenting no contraindications to bone marrow donation under general anaesthesia and to the required apheresis procedures;
• Written informed consent of the donor and patient.

You may not qualify if:

• Age \<40 years or \> 55 years
• Organic disease contraindicating the utilisation of myeloablative conditioning
• History of allogeneic Hematological Stem Cell Transplantation (HSCT);
• History of autologous HSCT \<1 year prior to the date for the scheduled allogeneic HSCT;
• Neurological location of the haemopathy justifying the transplantation;
• Pregnant or breastfeeding woman;
• Positive HIV serology;
• Positive hepatitis B or hepatitis C serology (except for post-vaccinal hepatitis B status);
• Absence of informed consent from the receiver or donor;
• Inability to adhere to the protocol instructions.

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead
• Etablissement Français du Sang: collaborator
• Bellicum Pharmaceuticals: collaborator

Study Sites (1)

CHU Jean Minjoz

Besançon, 25000, France

Location

MeSH Terms

Conditions

Graft vs Host Disease; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• DECONINCK Eric, MD, PhD, HDR

  CHRU de Besançon

  PRINCIPAL INVESTIGATOR

• Christophe FERRAND, PhD, HDR

  EFSBFC-INSERM UMR1098

  STUDY CHAIR

• Marina DESCHAMPS, PhD

  EFSBFC-INSERM UMR1098

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2016
• First Posted: July 29, 2016
• Study Start: April 10, 2019
• Primary Completion: December 26, 2021
• Study Completion: December 26, 2021
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

FR (1)