Neoplasms

Blood and Lymph Conditions

All Conditions

Behaviors and Mental Disorders

Immune System Diseases

Rare Diseases

Hematologic Neoplasms

Suicide

Graft vs Host Disease

Hematologic Diseases

Homologous Wasting Disease

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

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)

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

T lymphocytes iCASP9 ΔCD19

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.

Dimerizer drug AP1903

Eric DECONINCK, MD, PhD, HDR

Fabrice LAROSA, MD

DECONINCK Eric, MD, PhD, HDR

Christophe FERRAND, PhD, HDR

Marina DESCHAMPS, PhD

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

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.

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

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

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.

Bone marrow smear analysis.

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

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

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

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)

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.

Etablissement Français du Sang

Bellicum Pharmaceuticals

Centre Hospitalier Universitaire de Besancon

Skin and Connective Tissue Diseases

Infections

Melanoma

Herpes Simplex

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Self-Injurious Behavior

Behavioral Symptoms

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Analgesics

Vaccines

Molgramostim

Sargramostim

Interleukin-2

Intra and peritumoral infiltrates with multiple injections of lipoplexes carrying the HSVtk suicide gene co-administered with GCV and subcutaneous vaccine produced with formolized allogeneic tumor extracts and lipoplexes carrying hIL-2 and hGM-CSF genes.

1. Intra and peritumoral infiltrates with multiple injections of 0.1 ml/cm2 or 0.2 ml/cm3 of lipoplexes bearing the HSVtk suicide gene (1: 1; 1 mg/ml, according to tumor size), co-administered with GCV (12.5 mg/ml). Patients start with a minimum of 0.5 ml and at the 3rd week, the maximum dose is scaled according to the tumor size up to 2 ml maximum.
2. Treated simultaneously with a subcutaneous vaccine produced with:

   * Formolized allogeneic tumor extracts and,
   * Lipoplexes carrying hIL-2 and hGM-CSF genes (0.5 mg each).

Suicide plus immunogene therapy

Ventura Simonovich, MD

Safety evaluation of combined immunogene therapy in patients with advanced melanoma.

This phase I clinical protocol is proposed to evaluate the safety of combined immunotherapy genetics in humans.

This treatment combines the high local cytotoxicity of the suicide gene system (HSV thymidine kinase: HSVt k) / prodrug (ganciclovir: GCV) with the immunostimulation of interleukin2 (hIL2) and immunoamplification of granulocyte and macrophage colony stimulating factor (hGMCSF) in the presence of tumor antigens.

The proposed scheme consists in the periodic intra / peritumoral application of plasmid DNA complexes: cationic lipid (lipoplexes) containing the HSVtk gene, co-administered with the prodrug GCV, and subcutaneous injections of a vaccine (LGvax) produced with formolized extracts of allogeneic melanoma combined with lipoplexes carrying the hIL2 and hGMCSF genes.

Suicide Plus Immune Gene Therapy for Advanced Melanoma

Phase 1 Suicide Plus Immune Gene Therapy for Advanced Melanoma

Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 (https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf).

Instituto de Oncología Ángel H. Roffo

National Agency for Scientific and Technological Promotion, Argentina

National Council of Scientific and Technical Research, Argentina

University of Buenos Aires

Hospital Italiano de Buenos Aires

Medical Doctor

Symptoms and General Pathology

Syndrome

Lymphoma

Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Preleukemia

Myelodysplastic Syndromes

Bone Marrow Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Myeloid Leukemia

Acute Myeloid Leukemia

Lymphosarcoma

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

2x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant.

Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

5x10E5 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant.

Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

1x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant.

Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

3x10E6 BPX-501 (rivogenlecleucel) cells per kg infused after TCR alpha beta depleted donor stem cell transplant .

Rimiducid: Dimerizer drug administered by intravenous infusion in those subjects with acute GVHD with no response to steroids and/or other aGVHD medications or worsening in stage or grade of aGVHD after 48 hours. Subjects with chronic GvHD who do not respond to steroids/systemic therapies within 7 days, or there is a worsening in cGVHD, patients may then receive rimiducid.

Subjects will receive 2x10E5 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.

BPX-501 dose 1

Dimerizer drug administered by intravenous infusion in those subjects who develop GVHD after infusion of BPX-501 cells.

Rimiducid

Subjects will receive 5x10E5 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.

BPX-501 dose 2

Subjects will receive 1x10E6 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.

BPX-501 dose 3

Subjects will receive 3x10E6 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.

BPX-501 dose 4

all subjects will receive an alpha beta depleted donor transplant as part of treatment

This study will evaluate patients with blood cell cancers who are going to have an allogeneic (donor) blood stem cell transplant from a partially matched relative. The research study will test whether immune cells, called T cells, which come from the donor relative and are specially grown in the laboratory and then given back to the patient along with the stem cell transplant (T cell addback), can help the immune system recover faster after the transplant. As a safety measure, these T cells have been "programmed" with a "self-destruct switch" so that if, after they have been given to the patient, the T cells start to react against the tissues (called "graft versus host" disease, GVHD), the T cells can be destroyed.

This is a Phase1/2 dose escalation study evaluating the safety and feasibility of BPX-501 infused after partially mismatched, related (haploidentical), T cell-depleted HSCT. The purpose of this clinical trial is to determine whether BPX-501 infusion can facilitate engraftment, enhance immune reconstitution and potentially improve the graft versus leukemia (GVL) effect, with the potential for reducing the severity and duration of severe acute graft versus host disease (GvHD). The trial will evaluate the treatment of GvHD by the infusion of dimerizer drug (Rimiducid) in those subjects who present with GvHD that does not adequately respond to standard of care therapy.

Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant

A Phase 1/2 Dose Escalation Study Evaluating Safety and Feasibility of BPX-501 T Cells After Partially Mismatched, Related, T Cell-Depleted HSCT (Hematopoietic Stem Cell Transplant)

To evaluate the safety of infusion of each of 4 dose cohorts of BPX-501 (2x105, 5x105, 1x106 and 3x106 cells/kg) after transplantation of partially mismatched T cell depleted hematopoietic stem cell transplant (HSCT)

To evaluate the safety of the infusion of the rimiducid in subjects who received BPX-501 and have developed visceral or steroid refractory graft-versus-host-disease

To determine the maximum dose of BPX-501 (up to 3x106 cells/kg) that results in an adjusted cumulative incidence by Day 100 of no more than 45% Grade II - IV aGVHD and / or no more than 17% Grade III -IV aGVHD.

To assess immune reconstitution for each dose cohort

Evaluation of neutrophil and platelet engraftment, kinetics of donor cell engraftment and graft failure

Incidence and severity of acute and chronic GvHD

Time to resolution of acute GvHD after administration of Rimiducid

Characterize the safety profile of BPX-501 including evaluation of high grade toxicity and infectious complications

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
T Lymphocytes (LT) Expressing iCASP9 and ΔCD19 in Allogeneic Haematopoietic Transplantation.	NCT02849886	Graft Versus Ho... Hematological M...	T lymphocytes i... Dimerizer drug ...	40 Years - 55 Years	Centre Hospitalier Universitaire de Besancon
T Lymphocytes (LT) Expressing iCASP9 and ΔCD19 in Allogeneic Haematopoietic Transplantation.	NCT02849886	Graft Versus Ho... Hematological M...	T lymphocytes i... Dimerizer drug ...	40 Years - 55 Years	Centre Hospitalier Universitaire de Besancon
Suicide Plus Immune Gene Therapy for Advanced Melanoma	NCT03338777	Melanoma	Suicide plus im...	18 Years -	Hospital Italiano de Buenos Aires
Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant	NCT01744223	Acute Lymphobla... Acute Myelogeno... Lymphoma Myelodysplastic...	BPX-501 dose 1 Rimiducid BPX-501 dose 2 BPX-501 dose 3 BPX-501 dose 4 SCT	18 Years - 65 Years	Bellicum Pharmaceuticals

Spots Global Cancer Trial Database for suicide gene

Every month we try and update this database with for suicide gene cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.