E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10000886 |
E.1.2 | Term | Acute myeloid leukemia |
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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 determine whether combination treatment with low dose cytarabine and lintuzumab confers a survival benefit over treatment with low dose cytarabine and placebo in patients 60 years of age and older with previously untreated AML. |
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E.2.2 | Secondary objectives of the trial |
• Compare the safety and tolerability of combined therapy of low dose cytarabine and lintuzumab to low dose cytarabine alone • Determine the lintuzumab pharmacokinetic profile and immunogenicity in older patients with previously untreated AML • Assess infections that require hospitalization or IV antibiotics, transfusion requirements (platelets and red blood cell), complete blood cell counts (CBC), and quality of life in this population
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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 inclusion criteria to be eligible for inclusion into the study: 1. Must have untreated, morphologically confirmed acute myeloid leukemia as defined by the World Health Organization (WHO) Classification that occurred de novo, after prior exposure to chemotherapy for a separate malignancy, or evolved from an antecedent hematologic disorder. 2. Must be at least 60 years of age at the time of informed consent. 3. Must have at least 20% blasts in blood or marrow as documented by morphologic evaluation. 4. Must have at least 50% of leukemic blasts that express the CD33 antigen, by flow cytometric evaluation. 5. Must have an ECOG performance status score of 0 to 2. 6. Must have WBC less than 30,000/μL (pre-study use of hydroxyurea to control WBC is acceptable). 7. Females must be of non-childbearing potential, defined as those who are postmenopausal greater than 2 years or who have had a tubal ligation or hysterectomy. 8. Males must agree to use an effective contraceptive method during the course of the study. 9. Must be available for periodic blood sampling, study-related assessments and management of toxicity at the treating institution and be willing to comply with the expected drug administration schedule. 10. After being informed of the potential benefits and risks of available treatment options, patients must have declined intensive chemotherapy for AML. 11. Must give written informed consent. |
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E.4 | Principal exclusion criteria |
If a patient is positive for ANY of the following exclusion criteria, the patient will not be eligible for inclusion into the study: 1. Must not have a known diagnosis of acute promyelocytic leukemia or chronic myeloid leukemia. 2. Must not have any other active non-hematologic malignancies treated with chemotherapy within the last 12 months. Exception: Patients whose AML has evolved from MDS may have had prior treatment with hypomethylating agents if the agents were discontinued ≥2 weeks prior to patient randomization. 3. Must not have received previous chemotherapy (except hydroxyurea) for AML. 4. Must not have received any investigational agent within 4 weeks prior to randomization. 5. Must not have the following baseline laboratory evaluations: a. Aspartate transaminase (AST) greater than or equal to 2.5 times the upper limit of normal (ULN). b. Total bilirubin greater than or equal to 1.5 times ULN. c. Serum creatinine greater than or equal to 3 times ULN. 6. Must not have within 7 days of randomization either a life-threatening infection or a positive blood culture. 7. Must not have known human immunodeficiency virus (HIV). 8. Must not have a history of allergic reaction to cytarabine or any other component of drug formulation. 9. Must not be taking chronic systemic steroids exceeding 7.5 mg/day prednisone or equivalent. 10. Must not be taking any other chronic systemic immunosuppressive medication (i.e., cyclosporine, azathioprine, mycophenylate mofetil). 11. Must not have any serious underlying medical condition within 12 months prior to randomization that, in the Investigator’s opinion, would impair his/her ability to receive or tolerate the planned treatment, including but not limited to cerebrovascular accident (i.e., CVA; stroke), myocardial infarction, unstable angina, and pulmonary disease requiring supplemental oxygen. 12. Must not have evidence of dementia or altered mental status that, in the Investigator’s opinion, would preclude understanding and rendering of informed consent. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary: • Overall Survival Secondary: • Infections or fevers of unknown origin requiring hospitalization or intravenous (IV) antibiotics • Transfusion requirements - Platelets - Red blood cells (RBC) • Complete blood counts (CBC) - Absolute neutrophil cell (ANC) counts - Platelet counts - Hemoglobin - Peripheral blasts Additional: • Pharmacokinetic profile • Immunogenicity • Quality of Life (QOL) assessments: FACT-Leu questionnaire |
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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 | Yes |
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 | 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) | 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 | 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) | 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.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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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The study will end when the last patient in survival follow up has his last update (patient status can be assessed via either actual visit to the physician’s office or by phone call). Alternatively, if/when the Sponsor is ready to close the study, patients who are in their survival follow up will receive their final follow up visit regardless of whether a full 12 months of follow up has ensued, and the study will be closed.
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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 |