| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated | |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 8.1 | | E.1.2 | Level | LLT | | E.1.2 | Classification code | 10000886 | | E.1.2 | Term | Acute myeloid leukemia | |
| 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 evaluate the safety and efficacy of the subcutaneous administration of homoharringtonine (HHT) in the treatment of patients with refractory or relapsed acute myeloid leukemia (AML) | |
| E.2.2 | Secondary objectives of the trial | | Secondary endpoints include duration of treatment response, survival, induction mortality and hospitalizations. | |
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria | 1.Male or non-pregnant female patients, 18 years or older, diagnosed with refractory (no response to a previous combined chemotherapy including at least cytarabine + one anthracycline) or relapsed acute myeloid leukemia (AML)
2.Patients must not qualify for other alternative therapy of higher order. This restriction does not apply to other treatments such as hormonal therapy or biological response modifiers.
3.Patients must have completed all previous anti-leukemic therapy (except leukapheresis) for at least 2 weeks prior to first planned dose of HHT and must have fully recovered from side effects of a previous therapy, unless disease progression necessitates early therapy. In patients with rapidly proliferating disease, hydroxyurea may be administered prior and during the first 9-day HHT administration course, if clinically indicated, to control disease. Leukapheresis is allowed up to 24 hours prior to registration.
4.All medications necessary for the treatment of other chronic patient conditions should be administered at a stable, maintenance dose for 30 days prior to the first study drug administration and during the course of study treatment, except in circumstances where therapeutic agents are administered on a sliding scale based upon changes in body weight, hematology or serum chemistry, e.g. insulin for diabetes.
5.ECOG performance status 0-2.
6.Life expectancy greater than 4 weeks.
7.Patients able to comply with the requirements of the entire study.
8.Patients able and willing to provide written informed consent prior to any study related procedure. (In the event that the patient is re-screened for study participation or a protocol amendment alters the care of an ongoing patient, a new informed consent form must be signed.)
9.Sexually active patients and their partners must use an effective double barrier method of contraception associated with a low failure rate (i.e., less than 1% per year) during and for six months after completion of study therapy. The following are considered effective contraceptives: (i) oral contraceptive pill, (ii) condom, (iii) diaphragm plus spermicide, (iv) abstinence, (v) patient or partner surgically sterile, (vi) patient or partner more than 2 years post-menopausal or (vii) injectable or implantable agent/device.
10.Patients must have health insurance or similar coverage
| |
| E.4 | Principal exclusion criteria | 1.Patients with NYHA class III or IV heart disease, active ischemia or any uncontrolled, unstable cardiac condition for which treatment for the condition is indicated but is not controlled despite adequate therapy, including angina pectoris, cardiac arrhythmia, hypertension or congestive heart failure.
2.Patients who have experienced a myocardial infarction in the previous 12 weeks.
3.Patients with any other concurrent illness which would preclude study conduct and assessment, including but not limited to another active malignancy (excluding squamous or basal cell skin cancer and in situ cervical cancer), uncontrolled and active infection, positive HIV status or positive HTLV I/II status, whether on treatment or not.
4.Patients with clinically significant Screening serum chemistry results which are not attributed to study disease, including but not limited to SGPT (ALT) >3 times the upper limit of normal, creatinine >2.0 mg/dl and bilirubin >2.0 mg/dl.
5.Patients who are pregnant or lactating.
6.Patients receiving systemic chemotherapy in the 2 weeks prior to the first study drug administration, unless treatment required for leukemia progression.
7.Patients with any medical or psychiatric condition, which may compromise the ability to give written informed consent or to comply with the study protocol.
8.Patient is enrolled in another clinical investigation within 30 days of enrollment or is receiving another investigational agent.
| |
| E.5 End points |
| E.5.1 | Primary end point(s) | Evaluation of tolerance
Efficacy endpoints: evaluation of response (CR, CRp, PR) | |
| 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 | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| 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 | 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 | 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) | 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 | 2 |
| 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 | Information not present in EudraCT |
| 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 | |
| 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 | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
