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Graft Versus Host DiseasePhase 1/2Side_by_CideNCT02849886

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

A Phase 1/2 study testing T lymphocytes iCASP9 ΔCD19 and Dimerizer drug AP1903 in people with Graft Versus Host Disease and Hematological Malignancies, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 40 to 55 years
What is being tested?
T lymphocytes iCASP9 ΔCD19 and Dimerizer drug AP1903
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
2 participants
Where
1 siteFrance
Study dates
10 Apr 2019to 26 Dec 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 40 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

1 site in 1 country.

France1 site

  • CHU Jean Minjoz

    Besançon, 25000

Other trials in France

About this study

Official title: Use of Genetically Modified T-lymphocytes Expressing the Inducible Human Caspase 9 Gene (iCASP9) and the Selection Gene ΔCD19 in Allogeneic Haematopoietic Transplantation.

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

Read the detailed description

Haematopoietic transplantation may result in serious complications, notably graft versus host disease (GvHD).

T-lymphocyte depletion of the bone marrow graft is able to prevent GvHD, while increasing the risk of rejection and reducing the antileukaemic effect of the graft (graft versus leukaemia, GvL). In a previous study, the investigators showed that the ex vivo transfer of the Herpes simplex thymidine kinase suicide gene (HSV-TK) into the graft's T lymphocytes prior to reinjection was not associated with immediate toxicity, while allowing for the prolonged recirculation of genetically modified cells (GMC) and control of induced GvHD by ganciclovir (GCV). In addition, this study revealed the existence of GMC resistant to GCV, an immunodeficiency of transduced cells, as well as an increased risk of Epstein-Barr virus (EBV)-induced lymphoproliferative disease. To overcome these difficulties, investigators improved the methodology of producing GMC by using a new vector (pMSCV-iCASP9-2A-ΔCD19) whose susceptibility gene was of human origin and associated with a human surface marker (non-functional) enabling the cell selection process. Moreover, the demonstration that the induced GvHD in this setting could be controlled by the administration of GCV alone led to significantly increase the number of genetically modified T-lymphocytes administered and omit cyclosporin prophylaxis of GvHD.

This phase I study will include 12 patients and will be conducted according the dose escalation method (2.10e6, 5.10e6 and 10.10e6 GMC / kg respectively for levels I, II \& III). GMC will be prepared in the Cell and Tissue Engineering Laboratory (advanced therapy medicinal products departement) of the french Blood center (EFS) in Besançon, France, and sent to the transplantation department.

Being tested
T lymphocytes iCASP9 ΔCD19, Dimerizer drug AP1903
Keywords
GvHD, Suicide gene, Dimerizer drug AP1903, Hematological stem cell transplantation
Medical subject headings
Graft vs Host Disease, Hematologic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • T lymphocytes iCASP9 ΔCD19Drug

    Also called T lymphocytes Gene Modified Cells (GMC)

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

  • Dimerizer drug AP1903Drug

    Also called Dimerizer 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.
Study groups in NCT02849886
Study groupRoleWhat they receive
LT icasp9 ΔCD19 (cohort1)ExperimentalInjection T lymphocytes iCASP9 ΔCD19 (2.10e6, 5.10e6 and 10.10e6 Gene Modified Cells (GMC)/kg).
Receives: Drug: T lymphocytes iCASP9 ΔCD19
LT iCASP9 ΔCD19 & GvHD (cohort2)ExperimentalInjection 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)
Receives: Drug: T lymphocytes iCASP9 ΔCD19; Drug: Dimerizer drug AP1903

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. GvHD response to Dimerizer AP1903

    Disappearance of clinical signs of GvHD

    Measured: 72 hours after administration of Dimerizer AP1903

Secondary outcomes (5)

  1. Haematopoietic reconstitution (Blood)

    Full Blood count and Blood Cell phenotyping (T \& B Lymphocytes, Natural Killers cells (NK), polynuclear cells...)

    Hematopoietic reconstitution will be assessed when % of Blood cells reach normal account values.

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

  2. Haematopoietic engraftment (bone marrow)

    Bone marrow smear analysis.

    Haematopoietic engraftment will be assessed when proportion of marrow cells reach normal account values.

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

  3. Haematopoietic engraftment (chimerism)

    Chimerism Analysis by quantitative mesurement (mesure of % of Donor \& recipient cells)

    Full chimerism will be assessed when chimerim will reach 100% of donor profile.

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

  4. Infections post Transplantation

    Monitoring of Infections post-transplantation will be studied by analysis of frequency of infection's events.

    (number of infection's events by patients and/or frequency)

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

  5. GvL effect

    Molecular residual disease (MRD) analysis of biological markers of the initial hematological disease either by molecular biology and/or flow cytometry.

    GvL effect will be assessed by evaluation of decrease of initial tumoral load.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jul 2016 (estimated)
  2. Study start10 Apr 2019
  3. Primary completion26 Dec 2021
  4. Study completion26 Dec 2021

Why it stopped: not enough recruitment because of new therapeutic alternatives

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
2 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02849886
Sponsor's protocol ID
N/2000/39-B
Acronym
Side_by_Cide
Status last verified
Jul 2025
First submitted
19 May 2016
Last updated
9 Jul 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing T lymphocytes iCASP9 ΔCD19 and Dimerizer drug AP1903 in people with Graft Versus Host Disease and Hematological Malignancies, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 9 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: not enough recruitment because of new therapeutic alternatives). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

GvHD response to Dimerizer AP1903 (time frame: 72 hours after administration of Dimerizer AP1903). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02849886.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2025.

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