Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

PKC412 With or Without Itraconazole in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	MSKCC-02021 NOVARTIS-CPKC412A2104, NCI-G02-2107, UCLA-0305058-01, NCT00045578

Objectives

Primary

1. Determine the safety, tolerability, and pharmacokinetics of PKC412 with or without itraconazole in patients with acute myeloid leukemia or high-risk myelodysplastic syndromes.
2. Determine the pharmacodynamic activity of PKC412 on functional FLT3 inhibition in the cells of these patients.

Secondary

1. Determine the pharmacokinetics and total blood concentration of PKC412 and its metabolites in these patients.
2. Determine the biological and preliminary antitumor activity of these regimens in these patients.

Entry 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

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

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

Expected Enrollment

A total of 24 patients (12 per treatment group) will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Virginia Klimek, MD, Protocol chair		Ph: 212-639-6519; 800-525-2225

Jonsson Comprehensive Cancer Center at UCLA

Gary Schiller, MD, Principal investigator		Ph: 310-825-5513; 888-798-0719 Email: garyjs@ucla.edu

Registry Information
Official Title		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)
Trial Start Date		2002-03-12
Registered in ClinicalTrials.gov		NCT00045578
Date Submitted to PDQ		2002-07-16
Information Last Verified		2005-05-04
NCI Grant/Contract Number		P30-CA08748

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