E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High risk acute leukemias in 1st or subsequent complete remission or in relapse. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054291 |
E.1.2 | Term | Acute leukemia (in remission) |
E.1.2 | System Organ Class | 100000013002 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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 |
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E.2.2 | Secondary objectives of the trial |
To compare overall survival (OS) in the two treatment arms
To compare the cumulative incidence of non-relapse mortality (NRM)
To compare the chronic graft-versus-host disease (GvHD)-free,
relapse-free survival (GRFS)
To compare the time to T-cell immune reconstitution
To compare the engraftment rate
To compare the cumulative incidence of grade II-IV acute GvHD
To compare the cumulative incidence of extensive chronic GvHD
To compare time to GvHD resolution and use of agents with
immunosuppressive activity
To compare the cumulative incidence of relapse (CIR)
To compare incidence and duration of infectious episodes and infectious disease mortality
To evaluate the acute and long-term toxicity related to the HSV-Tk infusions
To assess quality of life (QoL) and Medical Care Utilization (MCU) in both arms |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Pharmacoeconomy
Version: F
Data: 2017-06-23
Objective:to summarize and evaluate treatment group differences in total resource use, and more specifically, in resource use associated with diagnosis, monitoring and treatment of relevant events (i.e., acute and chronic GvHD, infectious episodes, etc).The analysis and reporting of resources use data will be handled separately from the clinical study report.
Quality of life
Title:Evaluation of Quality of life
Version: F
Data: 2017-06-23
Objective: summarize and evaluate treatment group differences in patient convenience and satisfaction. |
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E.3 | Principal inclusion criteria |
Patients ≥ 18 years with HCT comorbidity index < 3 (Appendix I)
- Any of the following conditions:
- AML and ALL in 1st complete remission (CR1)
- AML and ALL in 1st complete remission (CR) at high risk of relapse based on negative prognostic factors (for the definition of high-risk of relapse see Appendix H)
- AML and ALL in 2nd or subsequent CR
- secondary AML in CR
- AML and ALL in 1st or 2nd relapse or primary refractory
- 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 and donors, or independent witnesses 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. |
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E.4 | Principal exclusion criteria |
- Patients with life-threatening condition or complication other than their basic condition
- Contraindication to haploidentical HCT as defined by the Investigator
- Patients with active CNS disease
- Pregnant or lactation. Patients both males and females with reproductive potential (i.e. menopausal for less than 1 year and not surgically sterilized) must practice effective contraceptive measures throughout the study. Women of childbearing
potential must provide a negative pregnancy test (serum or urine) within 14 days prior to registration. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The disease-free survival (event-free survival, EFS) will be measured for
all patients from the date of randomization (regardless of disease status
at HCT) until the date of relapse (or progression), or death from any
cause, whichever occurs first. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monthly until 6 months from HCT, then at months 9 and and yearly until
relapse or progression. |
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E.5.2 | Secondary end point(s) |
• To compare overall survival (OS) in the two treatment arms
• To compare cumulative incidence of non-relapse mortality (NRM)
- To compare the chronic graft-versus-host disease (GvHD)-free,
relapse-free survival (GRFS)
• To compare time to T-cell immune reconstitution
• To compare engraftment rate
• To compare cumulative incidence of grade II-IV acute GvHD
• To compare cumulative incidence of extensive chronic GvHD
- To compare time to GvHD resolution and use of agents with
immunosuppressive activity
• To compare cumulative incidence of relapse (CIR)
• To compare incidence and duration of infectious episodes and infectious disease mortality
• To evaluate the acute and long-term toxicity related to the HSV-Tk infusions
• To assess quality of life (QoL) and Medical Care Utilization (MCU) in both arms |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1)OS measured from random date to death2) NRM defined as any death
without occurrence of relapse3)cGRFS defined as the time from the
date of randomization to cGvHD,relapse/progr/death4)IR defined as
time to reach a level of CD3+≥ 100/μl from two consecutive
observations5)EnGRaf will be defined as the persistent predefinite levels
of blood cells.5)Cum incidence of grade 2,3, or 4 acute GvHD from the
date of HCT.6)Cum incidence of cGVHD diagnosed and graded according
to standard NIH criteria computed from the date of HCT7)Duration of
GvHD episodes computed from the date of start to the date of resolution
and duration of immunosuppressive treatments administered for
controlling GvHD8)CIR will be defined on the basis of morphologic
evidence of leukaemia in bone marrow or other sites |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life assessment |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Haploidentical haematopoietic stem cells transplantation (without HSV-Tk) |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 35 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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for Study completion date means the end of the last visit of the center because only when close out visit is performed all the data have been validated and study documentation rechecked |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |