Know Cancer

or
forgot password

Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of KW-2449 in Acute Leukemias (AML), Myelodysplastic Syndromes (MDS), and Chronic Myelogenous Leukemia (CML)


Phase 1
18 Years
N/A
Not Enrolling
Both
Acute Myelogenous Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, Chronic Myelogenous Leukemia

Thank you

Trial Information

Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of KW-2449 in Acute Leukemias (AML), Myelodysplastic Syndromes (MDS), and Chronic Myelogenous Leukemia (CML)


This is a Phase I open-label dose escalation study of KW-2449 in subjects with acute
leukemias, high risk MDS, and CML who are not candidates for approved therapy. Over an
18-month period, the investigative sites collectively will enroll up to a total of 96
subjects. Subjects will be enrolled sequentially into 1 of 7 dose groups to evaluate 2
dosing schedules (Arm A = 14 consecutive days of dosing followed by a 7-28 day rest period
as determined by recovery from any acute hematologic and non-hematologic toxicities, or Arm
B = 28 consecutive days of dosing followed by a 7-28 day rest period, as determined by
recovery from any acute hematologic and non-hematologic toxicities). The safety of a dose
level in Arm A (14-day dosing regimen) will be established prior to enrollment of subjects
in the same dose level in Arm B (28-day dosing regimen).

In April 2007 the protocol was amended to discontinue Arm B (28 consecutive days of dosing).
The protocol will continue as planned for Arm A (14 days of consecutive dosing).

Enrollment will proceed until a maximum tolerated dose (MTD) has been established for each
study Arm. Once the MTD has been reached, 12 additional subjects, with 1 or more of the
hematologic conditions included in this study, may be enrolled at the MTD as an expanded
safety cohort.


Inclusion Criteria:



1. Histologically confirmed diagnosis of:

- AML (including APL refractory to all-trans retinoic acid and arsenic) that has
relapsed or was not responsive to prior chemotherapy;

- Relapsed/refractory ALL;

- CML that has failed to respond or has lost a response to imatinib; and

- Advanced MDS (INT-2 and High risk by IPSS) with failure or intolerance to
approved therapy.

2. ECOG Performance Status score of 0, 1, or 2;

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 ULN; serum bilirubin ≤ 2 mg/dL (serum
bilirubin may be ≤ 3.0 mg/dL in any subject with Gilbert's Syndrome); and

7. For females of childbearing potential, a negative serum pregnancy test. Subjects, of
childbearing potential, must use an Investigator-approved method of birth control.

Exclusion Criteria:

1. Candidates for approved therapies;

2. Concomitant treatment with any investigational agent, chemotherapy, radiotherapy, or
immunotherapy;

3. Active CNS leukemia;

4. 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;

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

6. Uncontrollable disseminated intravascular coagulation;

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

8. Radiotherapy, or lack of recovery of any radiotherapy-related acute toxicity, within
the 28 days preceding the first dose KW-2449;

9. Treatment with systemic therapy for the underlying hematologic condition, or lack of
recovery of toxicity from such treatment, within 28 days of the first dose of
KW-2449, with the following exceptions: hydroxyurea for treatment of
hyperleukocytosis (discontinued for at least 48 hours prior to the first dose of
KW-2449); imatinib (discontinued for at least 48 hours prior to the first dose of
KW-2449); and interferon (discontinued for at least 7 days prior to the first dose of
KW-2449);

10. Treatment with any other investigational agent, or lack of recovery of toxicity from
such treatment, within the 28 days preceding the first dose of KW-2449;

11. Positive serology for HIV;

12. 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;

13. Any evidence of chronic Graft versus Host Disease;

14. Active autoimmune disease requiring immunosuppressive therapy;

15. Female subjects who are pregnant or breast feeding;

16. Subjects of childbearing potential, unwilling to use an approved, effective means of
contraception in accordance with the institution's standards;

17. Known current drug or alcohol abuse;

18. 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; or

19. For any reason is judged by the Investigator to be inappropriate for study
participation, including an inability to communicate or cooperate with the
Investigator.

20. Hematopoietic growth factors (i.e., such as erythropoietin or darbepoetin alpha,
filgrastim [granulocyte colony-stimulating factor {G-CSF }], sargramostim
[granulocyte-macrophage colony-stimulating factor {GM-CSF}], or other thrombopoietic
agents) and corticosteroids within 14 days of study entry.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine maximum tolerated dose of KW-2449 using prespecified dose limiting toxicity definitions based on CTCAE, version 3.0 and to assess tolerability based on adverse events

Outcome Time Frame:

For duration of dosing

Safety Issue:

Yes

Principal Investigator

Matt Fujimori, MD

Investigator Role:

Study Director

Investigator Affiliation:

Kyowa Hakko Kirin Pharma, Inc.

Authority:

United States: Food and Drug Administration

Study ID:

2449-US-001

NCT ID:

NCT00346632

Start Date:

June 2006

Completion Date:

April 2008

Related Keywords:

  • Acute Myelogenous Leukemia
  • Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndromes
  • Chronic Myelogenous Leukemia
  • AML
  • ALL
  • MDS
  • CML
  • Kinase Inhibitor
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Myelodysplastic Syndromes
  • Preleukemia

Name

Location

M.D. Anderson Cancer CenterHouston, Texas  77030
Johns Hopkins HospitalBaltimore, Maryland  21287
Contact KyowaPrinceton, New Jersey  08540
Weill Cornell/New York Presbyterian HospitalNew York, New York  10021