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)”

RATIONALE: PKC412 and itraconazole may stop the growth of cancer cells by blocking the enzymes necessary for cancer cell growth.

PURPOSE: Phase I/II trial to study the effectiveness of PKC412 with or without itraconazole in treating patients who have acute myeloid leukemia or myelodysplastic syndrome.

Study Type: Interventional

Study Design: Treatment, Open Label

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.

Intervention(s) in this Clinical Trial

• Drug: itraconazole
• Drug: midostaurin

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Memorial Sloan-Kettering Cancer Center

Overall Clinical Trial Officials and Contacts

Virginia Klimek, MD Study Chair Memorial Sloan-Kettering Cancer Center  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00045578

Study ID Number: CDR0000256899

ClinicalTrials.gov Identifier: NCT00045578

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database