E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Platelet Transfusion Dependence in Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) according to FAB criteria |
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MedDRA Classification |
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 assess the clinical benefit of lonafarnib compared to placebo, where benefit is measured by proportion of subjects that achieved platelet transfusion independence for any 8-consecutive-week period after randomization without worsening of red blood cell (RBC) transfusion requirements or hemoglobin (untransfused) during the same 8-consecutive-week period of platelet transfusion independence. |
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E.2.2 | Secondary objectives of the trial |
To compare the hematologic response rate (complete remission, partical remission, hematologic improvement), 4-weekly RBC transfusion events (number of RBC transfusion events during a 4-week period), active bleeding events (number and severity), infections (number of CTCAE Grade 3 and 4 infections and days of acute antibiotic, antifungal and/or antiviral intervention), and safety between the two groups. Additionally subjects will be followed for survival. Pharmacokinetics, pharmacodynamics and pharmacogenomics will be assessed in a subject of subjects. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Subjects with de novo documented MDS or CMML according to FAB criteria Subjects who are platelet transfusion dependent over an 8-week retrospective and 4-week prospective screening period (with at least 1 and no more than 8 platelet transfusions per 4-week period). Platelet transfusion data collected in the 4-week prospective period must confirm the data collected during the retrospective period. Age of 18 years or older; ECOG performance status of 0 - 2. Greater than 12 weeks (from randomization on Day -1) from any investigational drug, any chemotherapy, radiotherapy, immunotherapy, and from any treatment for MDS/CMML other than best supportive care. Greater than 24 weeks (from randomization on Day -1) following bone marrow or peripheral stem cell transplantation or treatment with donor lymphocyte infusion. Greater than 12 weeks (from randomization on Day-1) from any treatment with Oprelvekin, and treatment with erythropoetin or darbopoetin, unless given in stable doses over the 12 week screening period. |
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E.4 | Principal exclusion criteria |
No secondary MDS No grade >= 2 nausea or >= 1 vomiting (despite adequate antiemetic treatment) or any other condition that could interfere with taking oral medication. No serum creatinine > 1.5 x upper limit of normal (ULN). No bilirubin > 2mg/dl with the exception of documented Gilbert's Syndrome. No AST/SGOT or ALT/SGPT > 2.5 x ULN, or Alkaline phosphatase > 4 x ULN. No current or prior treatment with farnesyl transferase inhibitors. No current treatment for MDS/CMML other than best supportive care. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The achievement of platelet transfusion independence for any 8-consecutive-week period with no worsening of RBC transfusion requirements or hemoglobin (untransfused) during the same 8-consecutive-week period. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Open-label option for non-responders on placebo at end of Cycle 3 |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 | Information not present in EudraCT |
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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Non response (not achieving platelet transfusion independence for at least 4-consecutive weeks) at the end of Cycle 3. Unacceptable toxicity. Transformation to Acute Myelogenous Leukemia (AML) |
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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 | 6 |
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 | 6 |