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Acute Myeloid LeukemiaPhase 1/2NCT01573247

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

A Phase 1/2 study testing AKN-028 in people with Acute Myeloid Leukemia, run by Akinion Pharmaceuticals AB at 8 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myeloid Leukemia
What is being tested?
AKN-028
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
8 sitesin 4 countries
Study dates
Dec 2011to Mar 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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;
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  • 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.

Trial locations and contacts

8 sites in 4 countries.

8 sites in 4 countries

Sweden3 sites

  • Sahlgrenska University Hospital

    Gothenburg

  • Orebro University Hospital

    Örebro

  • Uppsala University Hospital

    Uppsala, SE-751 85

Other trials in Sweden

Czechia2 sites

  • University Hospital Brno

    Brno, 625 00

  • University Hospital Kralovske Vinohrady

    Prague, 100 34

Other trials in Czechia

Poland2 sites

  • MTZ Clinical Research Inc.

    Warsaw, 02-106

  • Institute of Hematology and Transfusion Medicine

    Warsaw, 02-776

Other trials in Poland

United Kingdom1 site

  • St.Bartholomew's Hospital

    West Smithfield, EC1A 7BE

Other trials in United Kingdom

About this study

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)

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.

Being tested
AKN-028
Keywords
Acute myeloid leukemia, Refractory Acute myeloid leukemia, FLT3 inhibitor, kinase inhibitor
Medical subject headings
Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AKN-028Drug

    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.

Study groups in NCT01573247
Study groupRoleWhat they receive
AKN-028ExperimentalNot described
Receives: Drug: AKN-028

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Plasma pharmacokinetic profiles

    Measured: up to 3 months

  2. Adverse Events

    Safety follow up

    Measured: up to 3 months

Secondary outcomes (1)

  1. Response

    Biological respons

    Measured: participants will be followed for the duration of up to 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2012 (estimated)
  2. Study startDec 2011
  3. Primary completionMar 2016
  4. Study completionMar 2016

Why it stopped: During the study two patients have experienced serious liver events related to AKN-028. The risk-benefit balance was judged to be negative.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01573247
Sponsor's protocol ID
AKN001
Other IDs
2011-003285-33
Status last verified
Mar 2016
First submitted
28 Mar 2012
Last updated
25 Mar 2016
Results posted
No
Data monitoring committee
Yes

Publications

  • Eriksson A, Kalushkova A, Jarvius M, Hilhorst R, Rickardson L, Kultima HG, de Wijn R, Hovestad L, Fryknas M, Oberg F, Larsson R, Parrow V, Hoglund M. AKN-028 induces cell cycle arrest, downregulation of Myc associated genes and dose dependent reduction of tyrosine kinase activity in acute myeloid leukemia. Biochem Pharmacol. 2014 Jan 15;87(2):284-91. doi: 10.1016/j.bcp.2013.10.022. Epub 2013 Nov 4.

    PubMed 24200998

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing AKN-028 in people with Acute Myeloid Leukemia, run by Akinion Pharmaceuticals AB at 8 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Sweden, Czechia, Poland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: During the study two patients have experienced serious liver events related to AKN-028. The risk-benefit balance was judged to be negative.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma pharmacokinetic profiles (time frame: up to 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01573247, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2016.

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