An early phase study which aims to find a dose, asses safety and tolerability of AKN-028 in Patients with Acute Myelogenous Leukemia (AML)

• Conditions: Acute Myelogenous Leukemia (AML); MedDRA version: 17.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-003285-33-PL
• Lead Sponsor: Akinion Pharmaceuticals AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-11-18
• Last Update Posted: 25 April 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 55

Inclusion Criteria

Patients are eligible to be included in Part 1 or Part 2 of the study only if they meet all of the following criteria:
1. Provide written informed consent prior to Screening;
2. Male or female patients, age = 18 years;
3. For females of childbearing potential, a negative urine pregnancy test must be obtained prior to administration of AKN-028. Female patients, of childbearing potential, must use an Investigator-approved method of birth control (i.e. oral contraception, barrier contraception, intrauterine device) throughout the course of the study and for 30 days after the last dose of study drug. Male patients with female partners of childbearing potential must also use an Investigator-approved method of birth control throughout the course of the study and for 30 days after the last dose of study drug.;
4. Confirmed diagnosis of AML (= 20% blasts in bone marrow and/or peripheral blood) according to World Health Organization (WHO) classification (Swerdlow et al 2008) and meeting at least one of the following:
a) Newly diagnosed AML, but according to the clinical judgment of the principal investigator, patient is not a candidate for induction chemotherapy because of age, comorbidity, performance status, or other factors;
b) AML in first relapse with WBC < 60,000/mm^3 and ineligible for further intensive induction chemotherapy;
c) AML in second relapse with low peripheral blast count
(< 10,000/mm^3) and ineligible for intensive induction
chemotherapy;
d) Primary refractory disease, here defined as patients with AML not having achieved CR following up to 2 courses of chemotherapy for enrollment in Part 1, and patients with AML refractory following only one course of chemotherapy for enrollment in Part 2;
Note: Severe neutropenia per se (up to Grade 4) should be accepted if it is likely to be related to the AML. However, the severe neutropenia may be due to the recently administered chemotherapy (e.g. cytarabin). It may be prudent to perform a new bone marrow examination. In case the bone marrow is hypoplastic (due to cytarabin) the screening should be postponed and G-CSF should be administered for a short period and then the patient should be re-evaluated. In case the bone marrow is not hypoplastic but rather infiltrated with AML cells the patient can be screened.
5. Performance status of 0-3 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale;
6. Adequate organ function, including the following:
a) Serum creatinine = 2.0 mg/dL (176.8 µmol/L) during screening;
b) Aspartate aminotransferase (AST) and ALT = 1.5 x the upper limits of normal (ULN) during screening; and
c) Total bilirubin = 1.5 x ULN during screening.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 52
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 3

Exclusion Criteria

Patients will be excluded from the study if they meet any of the following criteria:
Part 1 or Part 2 Exclusions:
1. Patients who are candidates for induction chemotherapy for AML;
2. Total WBC count = 60,000 mm^3;
3. Evidence of active central nervous system (CNS) leukemia;
4. Evidence of blast-phase chronic myelogenous leukemia (CML);
5. Histological or cytogenetic diagnosis of AML with M3 subtype (Acute Promyelocytic Leukemia);
6. Lack of recovery of non-hematological toxicity from systemic therapy for the underlying hematologic condition;
7. Previous or concurrent malignancy except non-invasive non-melanoma skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 2 years prior to study entry; this exclusion does not refer to the disease (AML) under study;
8. Uncontrolled systemic infection (viral, bacterial, or fungal);
9. Uncontrolled disseminated intravascular coagulation;
10. Known positive serology for human immunodeficiency virus;
11. Clinically significant cardiac dysfunction (New York Heart Association Class 3 or 4) at the time of screening, or a history of myocardial infarction or heart failure within 3 months preceding the first dose of AKN-028;
12. Chronic Graft versus Host Disease (GVHD) with the exception of mild (Grade 1) skin or oral GVHD;
13. Major surgery within the 28 days preceding the first dose of AKN-028;
14. Concomitant administration of any other anti-leukemia or anti-neoplastic therapy (during the screening period, hydroxyurea is allowed for = 7 days before Cycle 1 as well as for = 7 days in between cycles);
15. Concomitant treatment with immunotherapy, or any investigational agent within 28 days preceding the first dose of AKN-028, or lack of recovery from toxicity of such treatment;
16. Active autoimmune disease requiring immunosuppressive therapy;
17. Radiotherapy, or lack of recovery of any radiotherapy-related acute toxicity, within the 28 days preceding the first dose of AKN-028;
18. Previous treatment in any clinical study with AKN-028, any other FLT3 inhibitor, or any other c-KIT inhibitor;
19. Female patients who are pregnant or breast-feeding;
20. Male, or female patients of childbearing potential, unwilling to use an approved, effective means of contraception (e.g., oral contraception, barrier contraception, intrauterine device) in accordance with the investigator’s standards;
21. Known current drug or alcohol abuse;
22. Active viral Hepatitis B and /or C;
23. Other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that, in the opinion of the investigator, may compromise the safety of the patient during the study, affect the patient’s ability to complete the study, or interfere with interpretation of study results;
24. Any condition, which is judged by the Investigator to be inappropriate for study participation, including an inability to communicate or cooperate with the Investigator and the requirements of this study.
Part 2 Only Exclusions:
25. AML secondary to previous malignant hematological disease, e.g. myelodysplastic syndrome, myeloproliferative neoplasms;
26. If 50% or more of cells in 2 or more myeloid lineage are dysplastic (AML with myelodysplasia related changes);
27. Primary refractory disease, defined as any patient not having achieved CR following =2 courses of standard chemotherapy;
28. Therapy-related AML resulting from prior exposure to

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified