E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High risk Acute Myeloid Leukaemia and Myelodysplasia |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10028532 |
E.1.2 | Term | Myelodysplasia |
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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
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 |
The purpose of this study is to investigate the feasibility and safety of using Clofarabine as pre-conditioning therapy in allogeneic transplant conditioning schedules for the treatment of high risk acute myeloid leukaemia or myelodysplasia.
The overall feasibility and safety of this approach will be determined by analysis of: 1. Time to engraftment 2. Incidence of severe (grade III-IV) Graft versus Host Disease 3. Incidence of other treatment-related toxicities 4. Early and late treatment related mortality and overall survival in this group of patients.
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E.2.2 | Secondary objectives of the trial |
Secondary objectives will be to evaluate: 1.The efficacy of this approach to induce durable remission in patients with high risk AML and MDS. 2.Relapse rate. 3.The role of Donor Lymphocyte Infusions in this setting 4.Recipient immune reconstitution parameters following this approach 5.The effect of this approach on overall duration of in-patient stay
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Cytologically and immunophenotypically (or immunohistochemically) confirmed diagnosis of high risk AML or MDS as defined by the following criteria: • Primary refractory disease as defined by failure to achieve complete remission after one course of intensive chemotherapy appropriate for the therapy of AML • Early relapse following induction or consolidation chemotherapy (within 12 months) • Second or subsequent relapse • AML secondary to documented myelodysplasia, myeloproliferative disorder or prior chemotherapy/radiation • Progressive myelodysplasia with excess blasts. • Poor risk cytogenetics 2.Minimum age of 18 years 3.Eligible for allogeneic stem cell transplant by local institutional guidelines 4.Suitable matched-related/sibling or volunteer unrelated donor available, as determined by local institutional guidelines 5.Negative pregnancy test for females of child-bearing potential within 7 days prior to the start of study treatment 6.If sexually active, male and female subjects must agree that they will use an effective method of birth control throughout the active study period 7.Written informed consent 8.Capable of and willing to comply with scheduled visits, treatment plan and required laboratory tests 9.Adequate renal and hepatic function as indicated by defined laboratory criteria
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E.4 | Principal exclusion criteria |
1.Psychiatric, addictive or any disorder which compromises ability to give truly informed consent for participation in this study 2.Previous Allogeneic Bone Marrow or Peripheral Blood Stem Cell Transplant. 3.Pregnant or lactating women. All female subjects of child-bearing potential must have a negative pregnancy test within 7 days prior to the start of treatment. 4.Any current active, invasive malignancy excluding AML or MDS
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E.5 End points |
E.5.1 | Primary end point(s) |
Treatment related mortality (TRM) measured at day 100 and 1 year post transplant and cause of mortality |
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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) | 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) | 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 | No |
E.8.1.2 | Open | No |
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 | No |
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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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The trial will terminate at the last assessment visit of the last subject undergoing the trial. The last assessment for the purposes of the trial occurs at one year post transplant. |
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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 | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |