E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
(very) poor risk AML or RAEB with IPSS ≥ 1.5 |
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E.1.1.1 | Medical condition in easily understood language |
Acute myeloid Leukemia of myelodysplastic syndrome |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10024329 |
E.1.2 | Term | Leukemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028533 |
E.1.2 | Term | Myelodysplastic syndrome |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
*Phase I part
- To asses the safety and feasibility of post-transplant panobinostat combined with decitabine to a regimen of T-cell replete RIC alloHSCT in patient with very poor-risk AML/RAEB, and select the recommended dose level for part II of the study
*Phase II part
- To assess the feasibility and efficacy of addition of post-transplant panobinostat combined with decitabine to a regimen of T-cell replete RIC alloHSCT and DLI in patients with (very) poor-risk AML/RAEB |
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E.2.2 | Secondary objectives of the trial |
- Assess efficacy in terms of complete remission rate, overall and progression free survival.
- Assess toxicity |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with poor risk or very poor risk AML or RAEB with IPSS ≥ 1.5.
• Eligibility for continuation with intensive induction/consolidation chemotherapy
• Eligible for allogeneic donor search (related/unrelated)
• 18-70 years, inclusive
• Written informed consent
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E.4 | Principal exclusion criteria |
• History of active malignancy during the past 2 years with the exception of basal carcinoma of the skin or carcinoma “in situ” of the cervix or breast
• Known HIV-positivity
• Pregnant or breast-feeding female patients
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I part
• Feasibility of protocol treatment as defined by the number of DLTs during the first cycle PNB/DAC .
Phase II part
• Feasibility of protocol treatment as defined by percentage of patients actually receiving treatment according to protocol up to eligibility for the first DLI within 115 days.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation will take place when the required data are available and evaluated |
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E.5.2 | Secondary end point(s) |
• Response to first cycle PNB/DAC
• Response to second cycle PNB/DAC
• Percentage of successful donor searches
• Percentage of patients who received alloHSCT
• Best response on protocol
• Engraftment after alloHSCT
• Incidence and severity of acute and chronic GvHD
• (Serious) adverse events
• Overall survival (OS) from registration and start of protocol treatment
• PFS from registration and from start of protocol treatment
• NRM rate
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Last patient, last visit, 5 years after registration of the last patient, when the required data are available and evaluated |
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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 | Yes |
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 | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Belgium |
Netherlands |
Switzerland |
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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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Last patient, last visit. |
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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 | 7 |
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 | 7 |
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 |