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. |
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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 | 13.1 |
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 | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 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 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: B
Data: 2011-02-21
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).
Quality of life
Title:Evaluation of Quality of life
Version: B
Data: 2011-02-21
Objective: summarize and evaluate treatment group differences in patient convenience and satisfaction. |
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E.3 | Principal inclusion criteria |
• Age ≥ 18 with HCT comorbidity index < 3 (Appendix I)
• Any of the following conditions:
• 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
• Absence of timely and suitable fully HLA matched or one HLA locus mismatched family or unrelated donor and, at Investigator’s discretion, absence of other possible therapeutic alternatives
• 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 disease
• 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) |
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.5.1.1 | Timepoint(s) of evaluation of this end point |
Disease-Free Survival (DFS) Monthly (bone marrow aspiration: every 3 months, or as clinically indicated) for first 6 months after haplo-HCT and thereafter at month 9, 12 and yearly until disease relapse or death |
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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 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 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 |
•mthly up 6 mths after haplo-HCT,then at mth 9,12;yearly until death•weekly till IR, then mthly up 6 mths, at mth 9,12•weekly till IR, then mthly up 6 mths, at mth 9,12•weekly till IR,then mthly up 6 mths, at mth 9,12;yearly until death•weekly till IR, mthly up 6 mths•weekly till IR, mthly up 6 mths, at mth 9,12;yearly until death•Mthly(bone marrow aspiration:every 3 mths or as clinically indicated)up 6 mths, at mth 9,12;yearly until disease relapse•weekly till IR, mthly up 6 mths, at mth 9,12;yearly until death•on a weekly basis up to IR, mthly up 6 mths from the date of IR then at mth 9,12;yearly for long-term toxicity•QoL:at screening, mth 9,12;yearly till end of study.MCU on ongoing basis |
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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 | 12 |
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 re-checked. |
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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 | 3 |
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 |