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

Phase 1
18 Years
Not Enrolling
Acute Myelogenous Leukemia (AML)

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Trial Information

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

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

Inclusion Criteria:

1. 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.

2. Eastern Cooperative Oncology Group (ECOG) Scale score17 of 0, 1, or 2 (refer to
Appendix 1);

3. Male or female, at least 18 years of age;

4. Signed written informed consent;

5. Serum creatinine ≤ 2.0 mg/dL;

6. 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

7. For women of childbearing potential, a negative serum pregnancy test must be obtained
prior to administration of KW-2449.

Exclusion Criteria:

1. Subjects who are candidates for approved therapies for their underlying condition;

2. Prior treatment with KW-2449;

3. Concomitant treatment with chemotherapy (systemic or intrathecal), radiotherapy,
immunotherapy, or any investigational agent;

4. Evidence of active central nervous system (CNS) leukemia;

5. 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;

6. Uncontrolled systemic infection (viral, bacterial, or fungal);

7. Uncontrolled disseminated intravascular coagulopathy;

8. Major surgery within the 28 days preceding the first dose KW-2449;

9. Radiotherapy within the 28 days preceding the first dose KW-2449, or lack of recovery
from any radiotherapy-related acute adverse event;

10. 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.

11. 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;

12. Known positive serology for human immunodeficiency virus (type 1 and/or 2);

13. 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;

14. Chronic Graft versus Host Disease (GVHD) with the exception of mild (Grade 1) skin

15. Phase 1 only: ≥ Grade 2 nausea or vomiting within 7 days preceding the first dose
KW 2449;

16. Active autoimmune disease requiring immunosuppressive therapy;

17. 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

18. 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.

19. Known current drug or alcohol abuse;

20. 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;

21. 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;

22. 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

23. Monoamine oxidase-B (MAO-B) or aldehyde oxidase (AOX) inhibitors within 7 days
preceding the first dose KW-2449.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety as determine by adverse event rate and dose limiting toxicity

Outcome Time Frame:

Approximately 6 months

Safety Issue:



United States: Food and Drug Administration

Study ID:




Start Date:

January 2009

Completion Date:

December 2010

Related Keywords:

  • Acute Myelogenous Leukemia (AML)
  • Acute Myelogenous Leukemia
  • Safety
  • Dose Tolerance
  • Pharmacokinetics/Pharmacodynamics
  • FLT-3
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid



Johns Hopkins University Baltimore, Maryland  21205
University of Pennsylvania Philadelphia, Pennsylvania  19104
University of Maryland, Greenebaum Cancer Center Baltimore, Maryland  21201
St. Francis Hospital Greenville, South Carolina  29601