E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Immune Response and Minimal Residual Disease (MRD) in Adult Patients with Acute Myeloid Leukemia in First Complete Remission (CR1) |
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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 | 10000887 |
E.1.2 | Term | Acute myeloid leukemia in remission |
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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 |
The primary objectives of this study are to assess: 1. The quantitative and qualitative pharmacodynamic effects of Ceplene plus low dose IL-2 (Ceplene/IL-2) by monitoring T and NK cell phenotypes and their functionality after the first and third cycles of treatment in adult patients with acute myeloid leukemia (AML) in first complete remission (CR1).
2. Minimal residual disease (MRD) in AML patients receiving Ceplene/IL-2.
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E.2.2 | Secondary objectives of the trial |
The secondary objectives in this study are to document, in AML patients in CR1 treated with Ceplene/IL-2: 1. Leukemia-free survival (LFS) after a follow-up period of up to 2 years.
2. LFS by AML subgroup as defined by AML-specific cytogenetic markers identified at diagnosis.
3. The safety of Ceplene/IL-2 therapy.
4. The potential relationship of Ceplene/IL-2 effects on T and NK cell phenotypes and their functionality to MRD.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• AML patients in CR1 who have been cytogenetically well-characterized (using molecular cytogenetic techniques, eg, RQ-PCR) at diagnosis. Patients may be considered eligible if they have not had this assessment performed at diagnosis provided a viable diagnostic bone marrow sample is available on which this testing may be performed. • Characterization of leukemia immunophenotypic fingerprint at diagnosis using MFC techniques. • Bone marrow examination confirming CR (defined as less than 5% blasts in a normocellular bone marrow). • Eighteen years of age or older. • Patients have received any form of induction and consolidation therapy as per standard practice at the institution, including autologous stem cell transplantation (ASCT). • Within 6 weeks following the date of the last dose of consolidation or conditioning chemotherapy for AML, or following ASCT. • Platelet count recovered after chemotherapy to ≥75 x 109/L, and Partial Thromboplastin Time (PTT) within normal limits. • WBC ≥1.5 x 109/L and LFTs (to include SGPT [ALAT] or SGOT [AST] and bilirubin) should not exceed twice the upper limit of normal. • Serum creatinine less than or equal to 1.5 times the upper normal limit. • Able to function without significant decrease in daily activities (WHO Performance Status 0 - 1 or Karnofsky ≥70, refer to Appendix 1). • Life expectancy of more than three months and able to undergo routine outpatient evaluations for efficacy, safety, and/or compliance. • Women of childbearing potential must be practicing barrier or oral contraception, for the duration of the treatment, or documented as surgically sterile or one year post-menopausal. • If female, be non-nursing, non-pregnant and have a negative pregnancy test within two weeks of starting study drug. • The patient must be informed of the investigational nature of the study and written informed consent obtained.
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E.4 | Principal exclusion criteria |
• Patients who have undergone or are planned for allogeneic stem cell transplantation. • Patients with M3 as an AML subtype. • Class III or IV cardiac disease, hypotension or severe hypertension, vasomotor instability, serious or uncontrolled cardiac dysrhythmias (including ventricular arrhythmias) at any time, acute myocardial infarction within the past 12 months, active uncontrolled angina pectoris or symptomatic arteriosclerotic blood vessel disease. • Other active malignancies except in situ carcinoma of the cervix, localized squamous or basal cell carcinoma of the skin. • Serious concurrent or recent non-malignant medical conditions which, in the opinion of the Investigator, makes the patient unsuitable for participation in this study. • History of seizures, central nervous system disorders, stroke within the last 12 months, or psychiatric disability thought to be clinically significant in the opinion of the Investigator and adversely affecting compliance to protocol. • Patients unable to undergo repeat treatments, clinical evaluations and other diagnostic procedures required by the protocol. • Prior history of autoimmune disease (including but not limited to systemic lupus, inflammatory bowel disease, and psoriasis). • Patients with active peptic or esophageal ulcer disease or with past peptic ulcer or esophageal disease with a history or bleeding. • Patients requiring active treatment for hypotension. • Medical, sociologic, or psychological impediment to probable compliance with the protocol. • Patients continuing systemic treatment with clonidine, steroids, and/or H2 receptor blocking agents. • Patients with a history of hypersensitivity to histamine or histamine products, severe allergies to food or contrast media requiring treatment within the last five years.
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoints The quantitative and qualitative pharmacodynamic effects of Ceplene/IL-2 on the immune responses of T and NK cells will be assessed as follows:
1. Changes in T and NK cell phenotypes (CD56, CD3, CD4, CD8) in peripheral blood from Day 1 (baseline) to Day 21 of Cycle 1 and from Day 1 (pre-treatment Cycle 3) to Day 21 of Cycle 3.
2. Changes in immune response markers (CD3, NKp46 [and other NCRs], CD25, CD69, and IFN-γ) in peripheral blood from Day 1 (baseline) to Day 21‡ of Cycle 1 and from Day 1 (pre-treatment Cycle 3) to Day 21 of Cycle 3.
3. MRD will be evaluated by MFC in patients receiving Ceplene/IL-2. Immunophenotyping will be performed on fresh BM samples post-consolidation (at enrollment to serve as a baseline MRD measure) and within ten days following completion of Cycles 3 and 5, corresponding to ~3 and ~6 months after therapy initiation, respectively, to evaluate the number of residual leukemic cells (RLCs) present in BM at each timepoint.
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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 | Yes |
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 | 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
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |