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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)


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Leukemia, Myelodysplastic Syndromes

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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 UCLALos Angeles, California  90095-1781