An Open-Label, Phase II (Proof Of Concept) Trial Of PKC412 Monotherapy In Patients With Acute Myeloid Leukemia (AML) And Patients With High Risk Myelodysplastic Syndrome (MDS)
18 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
An Open-Label, Phase II (Proof Of Concept) Trial Of PKC412 Monotherapy In Patients With Acute Myeloid Leukemia (AML) And Patients With High Risk Myelodysplastic Syndrome (MDS)
OBJECTIVES:
Primary
- Determine the safety, tolerability, and pharmacokinetics of PKC412 with or without
itraconazole in patients with acute myeloid leukemia or high-risk myelodysplastic
syndromes.
- Determine the pharmacodynamic activity of PKC412 on functional FLT3 inhibition in the
cells of these patients.
Secondary
- Determine the pharmacokinetics and total blood concentration of PKC412 and its
metabolites in these patients.
- Determine the biological and preliminary antitumor activity of these regimens in these
patients.
OUTLINE: This is an open-label, multicenter study. Patients are stratified according to FLT3
status (wild type vs mutated). Patients are assigned to 1 of 2 treatment groups.
- Group I: Patients receive oral PKC412 twice daily on days 1-28.
- Group II: Patients receive PKC412 as in group I. Patients also receive oral
itraconazole twice daily on days 22-28.
In both groups, courses repeat every 28 days in the absence of disease progression or
unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 24 patients (12 per treatment group) will be accrued for this
study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- One of the following diagnoses:
- Acute myeloid leukemia, meeting 1 of the following criteria:
- Ineligible for myelosuppressive chemotherapy
- Relapsed or refractory disease after standard therapy and not likely to
require cytoreductive therapy within 1 month
- Myelodysplastic syndromes of 1 the following types:
- Refractory anemia with excess blasts (RAEB)
- RAEB in transformation
- Chronic myelomonocytic leukemia
- Documented wild type or mutated FLT3
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- WHO 0-2
Life expectancy
- At least 3 months
Hematopoietic
- Not specified
Hepatic
- SGOT or SGPT ≤ 3 times upper limit of normal (ULN)
- Bilirubin ≤ 2 times ULN
Renal
- Creatinine ≤ 1.5 times ULN
Pulmonary
- No pulmonary infiltrate on baseline chest x-ray that is known to be new within the
past 4 weeks
Gastrointestinal
- No gastrointestinal function impairment
- No gastrointestinal disease that would significantly alter the absorption of study
drug
Other
- No uncontrolled active infection
- No other concurrent severe and/or uncontrolled medical or psychiatric condition that
would preclude study participation
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
- At least 2 months since prior allogeneic, syngeneic, or autologous bone marrow or
stem cell transplantation
Chemotherapy
- See Disease Characteristics
- Recovered from prior cytotoxic chemotherapy
- At least 1 week since prior hydroxyurea
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- At least 4 weeks since prior anticancer therapy
- No more than 2 prior regimens for primary refractory or relapsed disease
- No prior FLT3 inhibitor therapy
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
Virginia Klimek, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000256899
NCT ID:
NCT00045578
Start Date:
March 2002
Completion Date:
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- recurrent adult acute myeloid leukemia
- refractory anemia with excess blasts
- refractory anemia with excess blasts in transformation
- secondary myelodysplastic syndromes
- untreated adult acute myeloid leukemia
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |
