A Phase IB, Open-Label Study to Determine the Safety and Pharmacokinetics of Twice Daily Oral Dosing of PKC412 Administered in Combinations Sequentially and Concomitantly With Daunorubicin and Cytarabine for Standard Induction Therapy, and High Dose Cytarabine for Consolidation in Patients With Acute Myeloid Leukemia (AML)
- Determine the safety and tolerability of PKC412 administered sequentially or
concurrently with induction chemotherapy comprising daunorubicin and cytarabine
followed by consolidation therapy comprising high-dose cytarabine in patients with
newly diagnosed acute myeloid leukemia.
- Compare the pharmacokinetics of these regimens in these patients.
- Determine the efficacy of these regimens, in terms of response rate, disease-free
survival, and overall survival, in these patients.
- Correlate genetic variation in drug metabolism genes, leukemia genes, and drug target
genes with response in patients treated with these regimens.
OUTLINE: This is an open-label, multicenter study. Patients are alternately assigned to 1 of
2 induction treatment groups.
- Induction therapy:
- Group I (sequential therapy): Patients receive daunorubicin IV over 30 minutes on
days 1-3, cytarabine IV continuously on days 1-7, and oral PKC412 twice daily on
days 8-21 in the absence of disease progression or unacceptable toxicity.
- Group II (concurrent therapy): Patients receive daunorubicin and cytarabine as in
group I and oral PKC412 twice daily on days 1-7 and 15-21 in the absence of
disease progression or unacceptable toxicity.
In both groups, patients are evaluated on day 28. Patients with persistent disease receive a
second induction course comprising daunorubicin IV over 30 minutes on days 1 and 2,
cytarabine IV continuously on days 1-5, and oral PKC412 on the same schedule as their
assigned treatment group. Patients with a complete response after course 1 or course 2
proceed to consolidation therapy.
- Consolidation therapy: Patients in both groups receive high-dose cytarabine IV over 3
hours twice daily on days 1, 3, and 5 and oral PKC412 on the same schedule as their
assigned treatment group. Treatment repeats every 28-42 days for 3 courses in the
absence of disease progression or unacceptable toxicity.
After completion of consolidation therapy, patients in both groups continue to receive
PKC412 alone, according to their assigned treatment group, every 28-42 days for up to 3
years in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Ronald Paquette, MD
Jonsson Comprehensive Cancer Center
United States: Food and Drug Administration
|Jonsson Comprehensive Cancer Center at UCLA||Los Angeles, California 90095-1781|
|MD Anderson Cancer Center/University of Texas||Houston, Texas 77030|
|Dana Faber Cancer Institute||Boston, Massachusetts 02115|
|Wayne State University/Karmanos Cancer Institute||Detroit, Michigan 48201|