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| ID | Type | Description | Link |
|---|---|---|---|
| 2009-012973-37 | Registry Identifier | EUdraCT number |
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EMA withdrew the marketing Authorisation at the request of AGC Biologics S.p.A (formerly MolMed S.p.A), which decided to permanently discontinue the marketing of the product for commercial reasons
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The main objective of this randomized trial is to compare disease-free survival (DFS) in high risk leukemia patients who underwent haploidentical HCT followed by an add back strategy of HSV-Tk donor lymphocytes or standard haploidentical HCT
Delayed immune-reconstitution remains one of the main limitation of haploidentical stem cell transplantation. The risk of severe infections remains high for several months and CD3+ reconstitution could take more than 10 months. The low number of lymphocytes infused with the graft, the degree of HLA (Human Leukocyte Antigen) disparity, and a reduced thymic function in adults and differences in host/donor antigen presenting cells are contributing causes.
The infusions of HSV-TK engineered lymphocytes may represent a significant therapeutic improvement in haploidentical HCT (hematopoietic cell transplantation), because it remarkably may enhance both GvL (Graft versus Leukemia) activity, thus reducing the occurrence of disease relapse, and post-transplant immune reconstitution in the absence of chronic immune suppression, thus decreasing the rate of both post-transplant opportunistic infections and transplant-related mortality. Furthermore, the efficient control of GvHD achieved via the suicide mechanism allows also the multiple infusion of HSV-TK-treated donor lymphocytes, when needed, that might further improve post-transplant host immune reconstitution, and survival in patients receiving haplo-HCT. Finally, this therapeutic approach can become a valuable option for all candidates, including patients with advanced disease and older age.
The proposed clinical trial represents an innovative therapeutic treatment for patients affected by high risk acute leukemia, who have undergone haploidentical stem cell transplantation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Experimental | HSV-TK engineering donor Lymphocytes |
|
| B | Active Comparator | T-cell depleted or T-cell replete strategies |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HSV-Tk | Genetic | Infusion of approximately 1±0.2 x 10^7 HSV-Tk genetically modified CD3+ cells/Kg between day +21 and day +49 after haploidentical HCT; in absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis. |
| Measure | Description | Time Frame |
|---|---|---|
| Disease-free Survival (DFS) | Defined as the measure from the date of randomization until the date of relapse (or progression), or death from any cause, whichever occurs first. Disease relapse or progression was determined by the Investigator based on the following disease examination:
| From the date of randomization, assessed up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) | any death without previous occurrence of a documented relapse (or progression).Patients alive or without any follow up will be censored. | From the date of randomization to the date of death, assessed up to 12 months |
| Immune Reconstitution (IR) |
Not provided
Inclusion Criteria:
Age ≥ 18 years
Any of the following conditions:
Family donor with patient-donor number of HLA mismatches ≥ 2 (full haploidentical), or family donors sharing one HLA-haplotype with the patient
Stable clinical conditions and life expectancy > 3 months
PS ECOG < 2
Serum creatinine < 1.5 x ULN
Bilirubin < 1.5 x ULN; transaminases < 3 x ULN
Left ventricular ejection fraction > 45%
QTc interval < 450 ms
DLCO > 50%
Patients, or legal guardians, and donors must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects
Exclusion Criteria:
Exclusion criteria for HSV-Tk infusion:
HSV-Tk cells can be administered after an adequate patient wash-out period (24 hours)
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| Name | Affiliation | Role |
|---|---|---|
| Antonio Lambiase, MD | AGC Biologics S.p.A. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Northwestern University Feinberg School of Medicine | Chicago | Illinois | 60611 | United States | ||
| Washington University Medical School |
No, only information requested by law will be released
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Planned sample size n.170; Randomized patients n. 92. Discontinued n. 70; Early termination by the Sponsor n. 22;
Study period:
Date of First patient enrolled: 12.04.2010; Date of Last patient completed: 30.11.2019; Date of End of study: 30.11.2019.
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| ID | Title | Description |
|---|---|---|
| FG000 | A-Experimental Arm | Patients received an infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg) followed by the infusion of HSV-TK genetically modified CD3+ cells. In absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis. HSV-TK engineering donor Lymphocytes |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 23, 2017 |
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| T-cell depleted or T-cell replete strategies | Other | Haploidentical HCT with the infusion of CD34+ cells plus a fixed dose of T cells (1 x 10^4/Kg) or unmanipulated haploidentical stem cell transplantation followed by high-dose cyclophosphamide as part of GvHD prophylaxis |
|
Assess how many patients experience IR. For the assessment, competing risk analysis was performed considering death, relapse, and disease progression as competing events. Patients who were still alive and had no recovery (IR) nor relapse (or progression) were censored.IR is defined as achieving a level of circulating CD3+ ≥ 100/μL for two consecutive observations. The following laboratory examinations are performed:
|
| Weekly up to IR after engraftment of HCT, monthly for 6 months from date of IR and then at month 9 and 12 |
| Engraftment Rate | Defined as the persistent blood cells count above predefined level. | At day 15 after HCT, monthly for 6 months after HCT and then at month 9 and 12 |
| Cumulative Incidence of Grade 2, 3, or 4 Acute GvHD (aGvHD) | Diagnosed and graded according to standard criteria. Grade 1: Skin: Stage 1-2: Rash on < 25% of skin or Rash on 25-50% of skin Liver: Stage 1-2: Bilirubin 2-3 mg/dl or Bilirubin 3-6 mg/dl Gastrointestinal: Stage 1-2: Diarrhoea > 500 ml/day or persistent nausea or Diarrhoea > 1000ml/day | from the date of HCT until the date of the first occurrence of aGvHD, assessed up to 6 months |
| Cumulative Incidence of Chronic GvHD (cGvHD) | Diagnosed and graded according to standard NIH consensus criteria | From the date of HCT until the date of the first occurrence of cGvHD, assessed up to 12 months |
| Duration of GvHD Episodes | Diagnosed and graded according to standard NIH consensus criteria | From the date of start until the date of resolution and duration of immunosuppressive treatments administered for controlling GvHD assessed up to 12 months |
| Cumulative Incidence of Relapse (CIR) | Defined on the basis of morphologic evidence of leukaemia in bone marrow or other sites. Gray's test was used to compare the sub-distribution functions of relapse (or progression) events in the two treatment groups. Patients alive without relapse (or regression) will be censored | from the date of randomization to the date of the first occurrence of relapse, assessed up to 12 months |
| Incidence and Duration of Infectious Episodes and Infectious Disease Mortality | Diagnosis, monitoring and treatment of infectious relevant events | From randomization to the date of resolution, assessed up to 12 months |
| Evaluate the Acute and Long-term Toxicity Related to the HSV-Tk Infusions | Toxicity profile of HSV-Tk infusions | From HSV-Tk infusions to the date of resolution, assessed up to 12 months |
| Quality of Life (QoL) and Medical Care Utilization (MCU) in Both Arms | Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters. | from randomization up to 12 months |
| Non-relapse Mortality (NRM) | Defined for all patients as any death without previous occurrence of a documented relapse (or progression). Absence of relapse was determined by the Investigator based on the following disease examination:
Gray's test was used to compare the sub-distribution functions of the death without previous relapse (or progression) and relapse (or progression) events in the two treatment groups. | From the date of randomization to the date of death, assessed up to 12 months. |
| St Louis |
| Missouri |
| 63110 |
| United States |
| John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey | 07601 | United States |
| Universitair Ziekenhuis | Ghent | Belgium |
| University Hospitals Leuven | Leuven | 3000 | Belgium |
| Centre Hospitalier Universitaire de Liège - Domaine Universitaire du Sart Tilman | Liège | Belgium |
| Hôpital Jean Minjoz | Besançon | 25030 | France |
| Centre Hospitalier Universitaire de Clermont-Ferrand | Clermont-Ferrand | France |
| Centre Hospitalier Régional Universitaire de Lille | Lille | France |
| Institut Paoli-Calmettes | Marseille | France |
| Centre Hospitalier Universitaire de Nantes | Nantes | France |
| Hôpital l'Archet | Nice | France |
| Hôpital Saint-Antoine | Paris | France |
| IUCT Oncopole - Institut Universitaire du Cancer de Toulouse | Toulouse | France |
| Charitè; Campus Benjamin Franklin | Berlin | 13353 | Germany |
| University Medical Center Hamburg-Eppendorf | Hamburg | Germany |
| Medizinische Hochschule Hannover | Hanover | 30625 | Germany |
| University of Leipzig | Leipzig | 04103 | Germany |
| Universitat Tubingen | Tübingen | 72076 | Germany |
| Medizinische Klinik und Poliklinik | Ulm | 89081 | Germany |
| George Papanicolaou Hospital | Thessaloniki | 57010 | Greece |
| Chaim Sheba Medical Center | Tel Litwinsky | 52621 | Israel |
| Azienda Sanitaria Ospedaliera S.Croce e Carle | Cuneo | CN | Italy |
| Azienda Ospedaliero-Universitaria Policlinico-Vittorio Emanuele | Catania | CT | Italy |
| Azienda Ospedaliera Universitaria Careggi | Florence | FI | Italy |
| Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello | Palermo | PA | Italy |
| Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Presidio Molinette | Torino | TO | Italy |
| Ospedale Santa Maria della Misericordia | Udine | UD | Italy |
| Policlinico G. B. Rossi, Azienda ospedaliera universitaria integrata di Verona | Verona | VR | Italy |
| Ospedale San Raffaele | Milan | Italy |
| Azienda Ospedaliero-Universitaria Policlinico di Modena | Modena | 41124 | Italy |
| Santaros Klinikos | Vilnius | Lithuania |
| Centro Hospitalar Lisboa Norte, E.P.E. | Lisbon | Portugal |
| Hospital de la Santa Creu i Sant Pau | Barcelona | Spain |
| Instituto Catalán de OncologÃa | L'Hospitalet de Llobregat | Spain |
| Hospital de Navarra | Pamplona | 31008 | Spain |
| B - Control Arm |
The physician could choose between the infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg) or unmanipulated haploidentical transplantation (bone marrow or peripheral blood) followed by high-dose cyclophosphamide. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | A - Experimental Arm | patients received the infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg), followed by the infusion of HSV-TK genetically modified CD3+ cells In absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis. |
| BG001 | B- Comparator Arm | the physician chose whether the patient received the infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg) or an unmanipulated haploidentical bone marrow or peripheral blood transplant followed by high-dose cyclophosphamide. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Disease-free Survival (DFS) | Defined as the measure from the date of randomization until the date of relapse (or progression), or death from any cause, whichever occurs first. Disease relapse or progression was determined by the Investigator based on the following disease examination:
| The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the "Intention to Treat Population" (ITT) and "Per Protocol" (PP) set populations. | Posted | Count of Participants | Participants | From the date of randomization, assessed up to 12 months |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival (OS) | any death without previous occurrence of a documented relapse (or progression).Patients alive or without any follow up will be censored. | TThe analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the "Intention to Treat Population" (ITT) and "Per Protocol" (PP) set populations. | Posted | Count of Participants | Participants | From the date of randomization to the date of death, assessed up to 12 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Immune Reconstitution (IR) | Assess how many patients experience IR. For the assessment, competing risk analysis was performed considering death, relapse, and disease progression as competing events. Patients who were still alive and had no recovery (IR) nor relapse (or progression) were censored.IR is defined as achieving a level of circulating CD3+ ≥ 100/μL for two consecutive observations. The following laboratory examinations are performed:
| The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the "Intention to Treat Population" (ITT) and "Per Protocol" (PP) set populations. | Posted | Count of Participants | Participants | Weekly up to IR after engraftment of HCT, monthly for 6 months from date of IR and then at month 9 and 12 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Engraftment Rate | Defined as the persistent blood cells count above predefined level. | Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure | Posted | At day 15 after HCT, monthly for 6 months after HCT and then at month 9 and 12 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cumulative Incidence of Grade 2, 3, or 4 Acute GvHD (aGvHD) | Diagnosed and graded according to standard criteria. Grade 1: Skin: Stage 1-2: Rash on < 25% of skin or Rash on 25-50% of skin Liver: Stage 1-2: Bilirubin 2-3 mg/dl or Bilirubin 3-6 mg/dl Gastrointestinal: Stage 1-2: Diarrhoea > 500 ml/day or persistent nausea or Diarrhoea > 1000ml/day | Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure | Posted | from the date of HCT until the date of the first occurrence of aGvHD, assessed up to 6 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cumulative Incidence of Chronic GvHD (cGvHD) | Diagnosed and graded according to standard NIH consensus criteria | Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure | Posted | From the date of HCT until the date of the first occurrence of cGvHD, assessed up to 12 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Duration of GvHD Episodes | Diagnosed and graded according to standard NIH consensus criteria | Due to the early termination of the study, the analysis was not performed.because data were not collected for this Outcome Measure | Posted | From the date of start until the date of resolution and duration of immunosuppressive treatments administered for controlling GvHD assessed up to 12 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Cumulative Incidence of Relapse (CIR) | Defined on the basis of morphologic evidence of leukaemia in bone marrow or other sites. Gray's test was used to compare the sub-distribution functions of relapse (or progression) events in the two treatment groups. Patients alive without relapse (or regression) will be censored | The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the "Intention to Treat Population" (ITT) and "Per Protocol" (PP) set populations. | Posted | Count of Participants | Participants | from the date of randomization to the date of the first occurrence of relapse, assessed up to 12 months |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Incidence and Duration of Infectious Episodes and Infectious Disease Mortality | Diagnosis, monitoring and treatment of infectious relevant events | Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure | Posted | From randomization to the date of resolution, assessed up to 12 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Evaluate the Acute and Long-term Toxicity Related to the HSV-Tk Infusions | Toxicity profile of HSV-Tk infusions | Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure | Posted | From HSV-Tk infusions to the date of resolution, assessed up to 12 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Quality of Life (QoL) and Medical Care Utilization (MCU) in Both Arms | Medical resource use data collected will be used in health economic analyses where it may be combined with other data from other sources such as cost data or other clinical parameters. | Due to the early termination of the study, the analysis was not performed because data were not collected for this Outcome Measure | Posted | from randomization up to 12 months |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Non-relapse Mortality (NRM) | Defined for all patients as any death without previous occurrence of a documented relapse (or progression). Absence of relapse was determined by the Investigator based on the following disease examination:
Gray's test was used to compare the sub-distribution functions of the death without previous relapse (or progression) and relapse (or progression) events in the two treatment groups. | The analysis has been performed for all patients in the two treatment arms. The NRM analysis was performed on the "Intention to Treat Population" (ITT) and "Per Protocol" (PP) set populations. | Posted | Count of Participants | Participants | From the date of randomization to the date of death, assessed up to 12 months. |
|
From day 21 through day 180 or at least 30 days after last dose of HSV-TK.
Safety analyses, Serious Adverse Events and all cause of mortality evaluations were performed on the STDP. STDP is defined as all randomized patients who received at least one haploidentical HCT (80 total patients).
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | A-Experimental Arm | Analysis performed only on Standard Population so, all randomized patients who received at least an infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg) followed by the infusion of HSV-TK genetically modified CD3. A total of 53/80 were included in the analysis | 35 | 53 | 35 | 53 | 22 | 53 |
| EG001 | B - Control Arm | Analysis performed only on Standard Population. The physician could choose between the infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg) or unmanipulated haploidentical transplantation (bone marrow or peripheral blood) followed by high-dose cyclophosphamide. A total of 27/80 were included in the analysis | 17 | 27 | 17 | 27 | 0 | 27 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Autoimmune haemolytic anaemia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Moderate Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Life threatening Febrile neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Life threatening Pancytopenia | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Severe Thrombotic microangiopathy | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Severe Thymic cyst | Blood and lymphatic system disorders | Systematic Assessment |
| ||
| Mild Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
| ||
| Severe Colitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Nausea | Gastrointestinal disorders | Systematic Assessment |
| ||
| Severe Stomatitis | Gastrointestinal disorders | Systematic Assessment |
| ||
| Severe Vomiting | Gastrointestinal disorders | Systematic Assessment |
| ||
| Moderate Pyrexia | General disorders | Systematic Assessment |
| ||
| Severe Pyrexia | General disorders | Systematic Assessment |
| ||
| Mild Acute graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Moderate Acute graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Severe Acute graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Mild Chronic graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Moderate Chronic graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Severe Chronic graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Moderate Graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Severe Graft versus host disease | Immune system disorders | Systematic Assessment |
| ||
| Severe Anal abscess | Infections and infestations | Systematic Assessment |
| ||
| Severe Bronchopulmonary aspergillosis | Infections and infestations | Systematic Assessment |
| ||
| Severe Cystitis klebsiella | Infections and infestations | Systematic Assessment |
| ||
| Moderate Cystitis viral | Infections and infestations | Systematic Assessment |
| ||
| Severe Cytomegalovirus colitis | Infections and infestations | Systematic Assessment |
| ||
| Cytomegalovirus colitis Cytomegalovirus colitis | Infections and infestations | Systematic Assessment |
| ||
| Severe Cytomegalovirus infection | Infections and infestations | Systematic Assessment |
| ||
| Severe Cytomegalovirus viraemia | Infections and infestations | Systematic Assessment |
| ||
| Moderate Device related infection | Infections and infestations | Systematic Assessment |
| ||
| Severe Device related infection | Infections and infestations | Systematic Assessment |
| ||
| Moderate Epstein-Barr virus infection | Infections and infestations | Systematic Assessment |
| ||
| Severe Epstein-Barr virus infection | Infections and infestations | Systematic Assessment |
| ||
| Moderate Gastroenteritis | Infections and infestations | Systematic Assessment |
| ||
| Moderate Herpes zoster infection neurological | Infections and infestations | Systematic Assessment |
| ||
| Severe Lung infection pseudomonal | Infections and infestations | Systematic Assessment |
| ||
| Moderate Otitis media acute | Infections and infestations | Systematic Assessment |
| ||
| Severe Pneumocystis jirovecii pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Moderate Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Severe Pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Life threatening pneumonia | Infections and infestations | Systematic Assessment |
| ||
| Severe Pneumonia cytomegaloviral | Infections and infestations | Systematic Assessment |
| ||
| Moderate Pneumonia klebsiella | Infections and infestations | Systematic Assessment |
| ||
| Severe Pneumonia klebsiella | Infections and infestations | Systematic Assessment |
| ||
| moderate Pneumonia pseudomonal | Infections and infestations | Systematic Assessment |
| ||
| Severe Salmonellosis | Infections and infestations | Systematic Assessment |
| ||
| Life threatening Sepsis | Infections and infestations | Systematic Assessment |
| ||
| Life threatening Septic shock | Infections and infestations | Systematic Assessment |
| ||
| Severe Skin infection | Infections and infestations | Systematic Assessment |
| ||
| Severe Soft tissue infection | Infections and infestations | Systematic Assessment |
| ||
| Moderate Staphylococcal infection | Infections and infestations | Systematic Assessment |
| ||
| Severe Systemic candida | Infections and infestations | Systematic Assessment |
| ||
| Life threatening Toxoplasmosis | Infections and infestations | Systematic Assessment |
| ||
| Severe Transaminases abnormal | Investigations | Systematic Assessment |
| ||
| Severe Cachexia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Life threatening Decreased appetite | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Severe Dehydration | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Severe Hyponatraemia | Metabolism and nutrition disorders | Systematic Assessment |
| ||
| Life threatening Acute lymphocytic leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Severe Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Severe Epstein-Barr virus associated lymphoproliferative disorder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Severe Leukaemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Life threatening leukaemia recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| Severe Post transplant lymphoproliferative disorder | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| ||
| moderate Dizziness | Nervous system disorders | Systematic Assessment |
| ||
| severe Epilepsy | Nervous system disorders | Systematic Assessment |
| ||
| moderate Neuropathy peripheral | Nervous system disorders | Systematic Assessment |
| ||
| Mild Haematuria | Renal and urinary disorders | Systematic Assessment |
| ||
| Life threatening Dyspnoea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Severe Hypoxia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Severe Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Severe Pneumonitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| ||
| Mild Rash | Skin and subcutaneous tissue disorders | Systematic Assessment |
| ||
| Life threatening Shock | Vascular disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| related to HSV-TK cells | Investigations | Systematic Assessment |
|
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Anna Stornaiuolo | AGC Biologics S.p.A | 00390221277440 | astornaiuolo@agcbio.com |
| Mar 8, 2021 |
| Prot_SAP_000.pdf |
| Male |
|
| Black |
|
| Caucasian |
|
| Other |
|
| Censored patients |
|
| DFS on PP Set |
|
|
| DFS on ITT - day 21 after transplant |
|
|
| DFS on PP Set day 21 after transplant |
|
|
| Superiority |
| Log Rank | 0.5995 | Superiority |
| DFS- Intention-To-Treat population - day 21 after transplant | Wilcoxon (Mann-Whitney) | 0.4078 | Superiority |
| DFS- Per-Protocol Set | Log Rank | 0.3351 | Superiority |
| DFS- Per-Protocol Set | Wilcoxon (Mann-Whitney) | 0.1233 | Superiority |
| DFS- Per-Protocol Set DFS-day 21 after transplant | Log Rank | 0.5995 | Equivalence |
| DFS- Per-Protocol Set DFS-day 21 after transplant | Wilcoxon (Mann-Whitney) | 0.4078 | Superiority |
|
|
|
|
|
|
| Participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
The physician could choose between the infusion of CD34+ cells plus a dose of T cells (approximately 1 x 104/Kg) or unmanipulated haploidentical transplantation (bone marrow or peripheral blood) followed by high-dose cyclophosphamide.
|
|
|
| Deaths |
|
| Deaths |
|
| Deaths |
|
| Deaths without previous immune reconstitution, relapse or progression |
|
| Patients with relapse or progression without previous immune reconstitution |
|
| Censored patients |
|
| Deaths without previous relapse or progression |
|
| Censored patients |
|
| Patients with relapse or progression |
|
| Censored patients |
|