E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myelogenous (Myeloid) Leukemia (AML) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000880 |
E.1.2 | Term | Acute myeloid leukaemia |
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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 assess the efficacy of clofarabine in combination with cytarabine compared with cytarabine alone in adult patients 55 years and older with AML who have either relapsed or are refractory after receiving up to two prior induction regimens, as measured by overall survival. |
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E.2.2 | Secondary objectives of the trial |
• To determine the overall remission (OR) rate (CR + CRi) of clofarabine in combination with cytarabine compared with cytarabine alone; • To determine the duration of remission and disease-free survival for each treatment group; • To compare treatment groups with respect to event-free survival and 4-month event-free survival; • To determine the safety and tolerability of clofarabine when used in combination with cytarabine compared with cytarabine alone and the duration, seriousness, severity and relationship of adverse events which occur during the treatment and follow-up period, including hospitalizations. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients must meet all of the following criteria to be eligible to participate in the study: (1) Provide signed, written informed consent. (2) Have a diagnosis of AML according to the WHO classification (see Appendix B of the study protocol). (3) Have received not more than 2 prior induction regimens for treatment of AML according to the following definitions and qualifications: • Induction regimen: a drug or combination of drugs administered for a pre-specified number of cycles (usually not exceeding 2 cycles total) to patients with AML with the intent of achieving a CR or CRi; • At least 1 prior induction regimen must have included cytotoxic chemotherapy; • Hematopoietic stem cell transplantation (HSCT) (administered after induction therapy) is not considered a distinct induction regimen. • Consolidation or maintenance regimens (administered after CR or CRi documented) are not considered distinct induction regimens. (4) Are refractory or relapsed (requiring at least 5% leukemic blasts in the bone marrow, regardless of the presence of other features such as new or recurrent dysplastic changes or extramedullary disease). (5) Be 55 years of age or older at the time of signing the informed consent. (6) Have an ECOG performance status (see Appendix C) score of 0, 1, or 2. (7) Be able to comply with study procedures and follow-up examinations. (8) Be nonfertile or agree to use birth control (ie, condom, diaphragm, cervical cap, etc) during the study and for at least 90 days after the last dose of study drug. (9) Have adequate renal and hepatic function as indicated by the following laboratory values: Renal-Estimated GFR : ≥60 mL/min/1.73m2 Hepatic- Serum bilirubin: ≤1.5 × ULN AST and ALT: ≤2.5 × ULN Alkaline phosphatase: ≤2.5 × ULN GFR = Glomerular filtration rate, as estimated by the Modification of Diet in Renal Disease (MDRD) equation (see appendix E) ULN = Institutional Upper Limit of Normal |
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E.4 | Principal exclusion criteria |
(1) Received previous treatment with clofarabine. (2) Received intermediate- or high-dose cytarabine (IDAC or HDAC, respectively) defined as a bolus administration schedule at ≥500 mg/m2/dose as a component of prior induction or consolidation therapy. (3) Have received an HSCT within the previous 3 months prior to study entry. (4) Have ≥ grade 2 acute graft versus host disease (GvHD). (5) Have either moderate or severe chronic GvHD, whether limited or extensive chronic GvHD. Patients with mild limited or extensive chronic GvHD may be included. (6) Are receiving any other systemic antileukemic therapy (standard or investigational). Patients must not have received previous therapy for at least 2 weeks prior to the first dose of study drug and must have recovered from any prior drug-related non-hematologic toxicity to ≤ grade 2, with the following exceptions: • hydroxyurea, which must not have been received <24 hours prior to the first dose of study drug; • monoclonal antibodies, which must not have been received for 6 weeks prior to the first dose of study drug. (7) Have psychiatric disorders that would interfere with consent, study participation, or follow-up. (8) Have a systemic fungal, bacterial, viral, or other infection not controlled. (9) Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver or other organ system that may place the patient at undue risk to undergo induction therapy with either or both of these agents. (10) Have been diagnosed with another malignancy, unless the patient has been disease free for at least 5 years following curative intent therapy. (11) Have clinical evidence suggestive of CNS involvement with leukemia unless a lumbar puncture confirms the absence of leukemic blasts in the CSF. (12) Known HIV positivity (13) Are pregnant or lactating. |
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E.5 End points |
E.5.1 | Primary end point(s) |
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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 | 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 | 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 | 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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | 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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See the study CLO-34100405 protocol |
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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 | |
E.8.9.1 | In the Member State concerned months | 48 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 48 |