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Acute Myelogenous Leukemia (AML)Phase 1NCT00779480

Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Study of KW-2449 in Acute Myelogenous Leukemia (AML) (Protocol Number: 2449-US-002)

A Phase 1 study testing KW-2449 in people with Acute Myelogenous Leukemia (AML), run by Kyowa Kirin Co., Ltd. at 4 sites in United States.

Terminated

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

Official record
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Trial summary

To determine the maximum tolerated dose of KW-2449 in people with acute myelogenous leukemia who are not candidates for approved therapy. As well, the study will determine the response rate to KW-2449. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Acute Myelogenous Leukemia (AML)
What is being tested?
KW-2449
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
14 participants
Where
4 sitesUnited States
Study dates
Jan 2009to Dec 2010
Phase
Phase 1
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

  • Histologically confirmed diagnosis of AML (excluding acute promyelocytic leukemia) that has relapsed or was not responsive to prior chemotherapy.
  • Phase 2: Only subjects with the FLT3/ITD mutation will be enrolled in Phase 2.
  • Eastern Cooperative Oncology Group (ECOG) Scale score17 of 0, 1, or 2 (refer to Appendix 1);
  • Male or female, at least 18 years of age;
  • Signed written informed consent;
  • Serum creatinine ≤ 2.0 mg/dL;
  • Serum SGOT (AST) and SGPT (ALT) ≤ 5x the upper limits of normal (ULN); serum bilirubin ≤ 2 mg/dL (serum bilirubin must be ≤ 3.0 mg/dL in any subject with Gilbert's Syndrome); and
  • For women of childbearing potential, a negative serum pregnancy test must be obtained prior to administration of KW-2449.

Who cannot join

  • Subjects who are candidates for approved therapies for their underlying condition;
  • Prior treatment with KW-2449;
  • Concomitant treatment with chemotherapy (systemic or intrathecal), radiotherapy, immunotherapy, or any investigational agent;
  • Evidence of active central nervous system (CNS) leukemia;
  • Previous or concurrent malignancy except noninvasive non-melanomatous 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;
  • Uncontrolled systemic infection (viral, bacterial, or fungal);
Show all 23Show fewer
  • Uncontrolled disseminated intravascular coagulopathy;
  • Major surgery within the 28 days preceding the first dose KW-2449;
  • Radiotherapy within the 28 days preceding the first dose KW-2449, or lack of recovery from any radiotherapy-related acute adverse event;
  • Treatment with approved systemic therapy for the underlying hematologic condition within 14 days of the first dose of KW-2449 with the exception of hydroxyurea (Hydrea®) or leukapheresis for hyperleukocytosis and/or thrombocytosis (see Concomitant Medication and Treatment), or lack of recovery from any adverse event from prior systemic therapy.
  • Treatment with another investigational agent within the 28 days preceding the first dose of KW-2449, or lack of recovery from any adverse event from such treatment;
  • Known positive serology for human immunodeficiency virus (type 1 and/or 2);
  • 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 KW-2449;
  • Chronic Graft versus Host Disease (GVHD) with the exception of mild (Grade 1) skin GVHD;
  • Phase 1 only: ≥ Grade 2 nausea or vomiting within 7 days preceding the first dose KW 2449;
  • Active autoimmune disease requiring immunosuppressive therapy;
  • Female subjects who are pregnant or breast feeding; Pregnant women are excluded from this study because the embryotoxic potential of KW-2449 is unknown. It is not known whether KW-2449 passes into human breast milk. Nursing mothers should not use KW-2449.
  • Male or female subjects of childbearing potential, unwilling to use an approved, effective means of contraception in accordance with the institution's standards; Pregnancy should be avoided in women receiving KW 2449 and in female partners of men receiving KW-2449. All subjects receiving KW-2449 should implement appropriate contraceptive methods.
  • Known current drug or alcohol abuse;
  • Other severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may compromise the safety of the subject during the study, affect the subject's ability to complete the study, or interfere with interpretation of study results;
  • Subject is judged by the Investigator to be inappropriate for study participation for any reason, including an inability to communicate or cooperate with the Investigator;
  • Use of hematopoietic growth factors (i.e., such as erythropoietin or darbepoetin alfa, filgrastim [granulocyte colony-stimulating factor {G-CSF}], sargramostim [granulocyte-macrophage colony-stimulating factor {GM-CSF}], or thrombopoietic agents) within 14 days preceding the first dose of KW-2449; or
  • Monoamine oxidase-B (MAO-B) or aldehyde oxidase (AOX) inhibitors within 7 days preceding the first dose KW-2449.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • University of Maryland, Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins University

    Baltimore, Maryland, 21231

  • St. Francis Hospital

    Greenville, South Carolina, 29601

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Study of KW-2449 in Acute Myelogenous Leukemia

To determine the maximum tolerated dose of KW-2449 in people with acute myelogenous leukemia who are not candidates for approved therapy. As well, the study will determine the response rate to KW-2449.

Read the detailed description

Phase 1: To determine the maximum tolerated daily dose (MTDD) of KW 2449 when administered to subjects with AML who are not candidates for approved therapy.

This was originally a Phase 1/Phase 2 study. However, a tolerable dose that had the potential for efficacy could not be identified in Phase 1. Therefore, Phase 2 was never conducted.

Being tested
KW-2449
Keywords
Acute Myelogenous Leukemia, Safety, Dose Tolerance, Pharmacokinetics/Pharmacodynamics, FLT-3
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.

  • KW-2449Drug

    KW-2449 50 mg capsules administered 3 or 4 times per day for 21-day cycles up to 6 cycles

Study groups in NCT00779480
Study groupRoleWhat they receive
KW-2449ExperimentalSequential dose escalation in separate cohorts of 3+3 design from 450 mg/day to 800 mg/day total daily dose.
Receives: Drug: KW-2449

What is being measured

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

  1. Safety as determine by adverse event rate and dose limiting toxicity

    Measured: Approximately 6 months

Secondary outcomes (1)

  1. Hematologic activity/improvement, Pharmacokinetics/Pharmacodynamics

    Measured: Approximately 6 months

Timeline

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

  1. First posted24 Oct 2008 (estimated)
  2. Study startJan 2009
  3. Primary completionApr 2010
  4. Study completionDec 2010

Why it stopped: Failure to demonstrate a tolerable dose that had potential for efficacy.

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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
14 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00779480
Sponsor's protocol ID
2449-US-002
Status last verified
Apr 2024
First submitted
22 Oct 2008
Last updated
25 Apr 2024
Results posted
No
Data monitoring committee
Yes

Publications

  • Pratz KW, Cortes J, Roboz GJ, Rao N, Arowojolu O, Stine A, Shiotsu Y, Shudo A, Akinaga S, Small D, Karp JE, Levis M. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009 Apr 23;113(17):3938-46. doi: 10.1182/blood-2008-09-177030. Epub 2008 Nov 24.

    PubMed 19029442

  • Shiotsu Y, Kiyoi H, Ishikawa Y, Tanizaki R, Shimizu M, Umehara H, Ishii K, Mori Y, Ozeki K, Minami Y, Abe A, Maeda H, Akiyama T, Kanda Y, Sato Y, Akinaga S, Naoe T. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17. doi: 10.1182/blood-2009-01-199307. Epub 2009 Jun 18.

    PubMed 19541823

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing KW-2449 in people with Acute Myelogenous Leukemia (AML), run by Kyowa Kirin Co., Ltd. at 4 sites in United States.

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 8 inclusion and 23 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 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. 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 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.

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: Failure to demonstrate a tolerable dose that had potential for efficacy.). 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?

Safety as determine by adverse event rate and dose limiting toxicity (time frame: Approximately 6 months). 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 NCT00779480, which also lists 2 linked publications.

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 Apr 2024.

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