Safety Study of AKN-028 in Patients With Acute Myelogenous Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Akinion Pharmaceuticals AB
Sponsor:
Information provided by (Responsible Party):
Akinion Pharmaceuticals AB
ClinicalTrials.gov Identifier:
NCT01573247
First received: March 28, 2012
Last updated: March 19, 2015
Last verified: March 2015
  Purpose

This Phase 1/2 study consists of two parts. The purpose of Part 1 of the study is to examine the safety and tolerability of AKN-028 and to determine the recommended dose of AKN-028 for further evaluation in Part 2 of the study in patients with Acute Myelogenous Leukemia (AML). The purpose of Part 2 of the study is to determine safety and efficacy in patients with AML.


Condition Intervention Phase
Acute Myeloid Leukemia
Drug: AKN-028
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1/2, Open-Label, Multi-Center Dose Escalation, Safety and Tolerability Study of AKN-028 in Patients With Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Akinion Pharmaceuticals AB:

Primary Outcome Measures:
  • Plasma pharmacokinetic profiles [ Time Frame: up to 3 months ] [ Designated as safety issue: Yes ]
  • Adverse Events [ Time Frame: up to 3 months ] [ Designated as safety issue: Yes ]
    Safety follow up


Secondary Outcome Measures:
  • Response [ Time Frame: participants will be followed for the duration of up to 3 months ] [ Designated as safety issue: No ]
    Biological respons


Estimated Enrollment: 55
Study Start Date: December 2011
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AKN-028 Drug: AKN-028

Part 1 of the study is a sequential dose-escalation evaluation of AKN-028. Part 1 started as an accelerated intra-patient dose escalation design in one patient at a time (the N=1 portion), and has switched to standard 3 + 3 design with inter-cohort dose escalation when AUC of 12 μM*hrs has been reached. Starting dose of AKN-028 was 60 mg twice a day.

During Part 2 of the study AKN-028 will be administered at the dose level selected in Part 1. Patients will be treated for a maximum of 3 cycles (first cycle of 14 days followed by 2 cycles of 21 days), with at least a 7-day treatment-free period between cycles. Patients with significant benefit after 3rd cycle may continue treatment at discretion of the investigator for as long as the patient continues to show significant benefit.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Provide written informed consent prior to Screening;
  • Male or female patients, age ≥ 18 years;
  • For females of childbearing potential, a negative urine pregnancy test must be obtained
  • Confirmed diagnosis of AML (≥ 20% blasts in bone marrow and / or peripheral blood) according to World Health Organization (WHO) classification [2] and meeting at least one of the following:

    1. 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;
    2. AML in first relapse with WBC < 60,000/mm3 and ineligible for further intensive induction chemotherapy;
    3. AML in second relapse with low peripheral blast count (< 10,000/mm3) and with WBC < 60,000/mm3 and ineligible for intensive induction chemotherapy;
    4. 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 1 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 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.

  • Performance status of 0-3 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale;
  • Adequate organ function, including the following:

    • Serum creatinine ≤ 2.0 mg/dL (176.8 mMol/L) during screening;
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x the upper limits of normal (ULN) during screening; and
    • Total bilirubin ≤1.5 x ULN during screening.

Exclusion Criteria:

  • Patients who are candidates for induction chemotherapy for AML
  • Total WBC count ≥ 60,000/mm3;
  • Evidence of active central nervous system (CNS) leukemia;
  • Evidence of blast-phase chronic myelogenous leukemia (CML);
  • Histological or cytogenetic diagnosis of AML with M3 subtype (Acute Promyelocytic Leukemia);
  • Lack of recovery of non-hematological toxicity from systemic therapy for the underlying hematologic condition;
  • 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;
  • Uncontrolled systemic infection (viral, bacterial, or fungal);
  • Uncontrolled disseminated intravascular coagulation;
  • Known positive serology for human immunodeficiency virus;
  • 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;
  • Chronic Graft versus Host Disease (GVHD) with the exception of mild (Grade 1) skin or oral GVHD;
  • Major surgery within the 28 days preceding the first dose of AKN-028;
  • 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 between cycles);
  • 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;
  • Active autoimmune disease requiring immunosuppressive therapy;
  • Radiotherapy, or lack of recovery of any radiotherapy-related acute toxicity, within the 28 days preceding the first dose of AKN-028;
  • Previous treatment in any clinical study with AKN-028, any other FLT-3 inhibitor, or any other c-Kit inhibitor;
  • Female patients who are pregnant or breast-feeding;
  • 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;
  • Known current drug or alcohol abuse;
  • Active viral Hepatitis B and /or C;
  • 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;
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01573247

Contacts
Contact: Maria Klockare +46 852486879 maria.klockare@akinion.com

Locations
Czech Republic
University Hospital Brno Suspended
Brno, Czech Republic, 625 00
University Hospital Kralovske Vinohrady Not yet recruiting
Prague, Czech Republic, 100 34
Poland
Institute of Hematology and Transfusion Medicine Recruiting
Warsaw, Poland, 02-776
MTZ Clinical Research Inc. Recruiting
Warsaw, Poland, 02-106
Russian Federation
Botkin City Clinical Hospital Not yet recruiting
Moscow, Russian Federation, 125284
First Pavlov State Medical University of St. Petersburg Not yet recruiting
St. Petersburg, Russian Federation, 197022
Sweden
Sahlgrenska University Hospital Recruiting
Gothenburg, Sweden
Orebro University Hospital Recruiting
Orebro, Sweden
Uppsala University Hospital Recruiting
Uppsala, Sweden, SE-751 85
United Kingdom
St.Bartholomew's Hospital Terminated
West Smithfield, United Kingdom, EC1A 7BE
Sponsors and Collaborators
Akinion Pharmaceuticals AB
Investigators
Principal Investigator: Martin Höglund, MD, PhD Dept of Hematology, Uppsala University Hospital
  More Information

No publications provided by Akinion Pharmaceuticals AB

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Akinion Pharmaceuticals AB
ClinicalTrials.gov Identifier: NCT01573247     History of Changes
Other Study ID Numbers: AKN001, 2011-003285-33
Study First Received: March 28, 2012
Last Updated: March 19, 2015
Health Authority: Czech Republic: State Institute for Drug Control
Czech Republic: Ethics Committee
Poland: The Central Register of Clinical Trials
Poland: Ethics Committee
Russia: Ministry of Health of the Russian Federation
Sweden: Medical Products Agency
Sweden: Regional Ethical Review Board
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Akinion Pharmaceuticals AB:
Acute myeloid leukemia
Refractory Acute myeloid leukemia
FLT3 inhibitor
kinase inhibitor

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on July 30, 2015