E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Myeloid Leukemia in Elderly patients in First Complete Remission |
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E.1.1.1 | Medical condition in easily understood language |
Cancer of white blood celles in Elderly patients |
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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 | 15.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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 |
To evaluate the efficacy of IPH2102 administered in patients with AML in first complete remission |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety of IPH2102 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Primary or secondary Acute Myeloid Leukemia in first CR/CRi, following induction chemotherapy and who received 1 or 2 consolidation cycles. Induction chemotherapy should be performed within 6 months before randomization. Consolidation cycle is defined as any chemotherapy administered within 3 months following CR and including aracytine irrespective of the administered dose(s). A minimum of one and maximum of 2 cycles should be administered before enrollment.
2) Patients not eligible for an allogeneic hematopoietic cell transplantation
3) Age 60 to 80
4) ECOG Performance status of 0 or 1
5) Clinical laboratory values at screening
• Calculated creatinine clearance (according to MDRD) > 60 ml/min/1.73 m2
• Platelet > 75 x 10 9/l
• Hemoglobin ≥ 10 g/dl supported or unsupported by transfusions
• ANC > 1 x 10 9/l
• Total Bilirubin levels ≤ 1.5 ULN
• ALT and AST ≤ 3 ULN
6) Recovery from acute toxicity of previous anti-tumor therapy
7) Male patients who accept and are able to use contraception methods recognized as highly effective
8) Signed informed consent prior to any protocol specific procedure.
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E.4 | Principal exclusion criteria |
1) Acute Promyelocytic Leukemia with t (15; 17), or its molecular equivalents (PML-RARA)
2) Favorable risk AML corresponding defined as t(8;21) or inv (16) and t(16;16) and their molecular equivalents (AML-ETO and CBFB-MYH11)
3) Last consolidation completed more than 3 months prior to first dosing
4) Concomitant treatment by chemotherapy, immunotherapy or by systemic corticosteroids
5) Within 28 days prior to first dosing: chemotherapy or systemic corticosteroid treatment
6) History of allogeneic hematopoietic cell transplantation or solid organ transplantation
7) History of high dose chemotherapy with autologous hematopoietic transplantation performed as treatment for AML
8) Use of any investigational agent within 2 months prior to the first dosing
9) Use of growth factors (G- or GM-CSF or EPO) within 28 days prior to first dosing
10) Any irradiation within the last 3 months except for analgesic intent
11) Intermittent or continuous renal replacement therapy
12) Abnormal cardiac status with any of the following
• Ejection fraction (measured by ultra-sound or radionuclide imaging) <50%
• Myocardial infarction within the previous 6 months
• QTc ≥ 480 ms (Bazett’s)
13) Current active infectious disease or positive serology for HIV, and/or HCV with detectable viremia and/ or HBV with positive Hbs Antigen and/or negative anti Hbs Antibody
14) Auto-immune disease:
• Which currently or previously required systemic immunosuppressive or immuno-modulatory therapy (including corticosteroids administered by systemic route)
• And/or has substantial probability to cause an irreversible injury to any tissue
• And/or is recent or unstable or has substantial risk to progress and cause severe complications
15) Serious concurrent uncontrolled medical disorder
16) History of another malignancy (apart from myelodysplastic syndromes, basal cell carcinoma of the skin, or in situ cervix carcinoma) except if free of disease for ≥ 3 years
17) Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
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E.5 End points |
E.5.1 | Primary end point(s) |
Leukemia-Free Survival calculated from the day of randomization until the occurrence of a relapse, as determined by an Independent Review Committee (IRC), or death from any cause, whichever occurs first. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Leukemia-Free Survival calculated from the day of randomization until the occurrence of a relapse, as determined by an Independent Review Committee (IRC), or death from any cause, whichever occurs first. |
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E.5.2 | Secondary end point(s) |
•Safety
Assessed using the CTCAE version 4.03 of June 14, 2010
•Efficacy
- Time to Relapse (TTR) measured from the day of randomization up to relapse
- Overall Survival (OS)
- Leukemia-Specific Survival (LSS)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety: from the time of patient signing the consent form until 28 days after the last administration or until the patient’s last study visit
Efficacy: from the day of randomization until the occurrence of a relapse, or death from any cause, whichever occurs first. |
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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 | No |
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 | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 50 |
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 | 40 |
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 | 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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End of Study visit will be performed immediately after relapse diagnosis, in case of premature withdrawal or at the end of the trial (when last patient has terminated the treatment period and when the 100 LFS events are reached to perform final analysis) |
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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 | 3 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |