Study of MK-8242 Alone and in Combination With Cytarabine in Participants With Acute Myelogenous Leukemia (P07649)

Official Title

A Phase I Study to Evaluate the Safety and Tolerability and Pharmacokinetic/Pharmacodynamics of MK-8242 Administered Alone and in Combination With Chemotherapy in Subjects With Refractory or Recurrent Acute Myelogenous Leukemia (Protocol No. P07649 (005))

Summary:

This is a study of MK-8242 alone and in combination with cytarabine in adult participants with refractory or recurrent acute myelogenous leukemia (AML). The study will have 2 Arms. Arm A is for participants with refractory or recurrent AML who are considered ineligible for standard chemotherapy. In Part 1 of Arm A, participants will receive MK-8242 monotherapy in escalating doses to determine the recommended phase 2 dose [RP2D]. In Part 2, participants will receive monotherapy with MK-8242 to confirm the RP2D and assess preliminary efficacy. Arm B is for participants with recurrent AML following an initial complete remission (CR) or CR with incomplete marrow recovery (CRi) of 6 to 12 months duration. In Part 1 of Arm B, participants will receive MK-8242 + cytarabine in escalating doses to determine the RP2D in combination with cytarabine. In Part 2, participants will receive MK-8242 + cytarabine to confirm the RP2D and assess preliminary efficacy. The pharmacokinetics of MK-8242 will be studied in both arms. With Amendment 4 (22 August 2013) a 21-day dosing cycle is added, with MK-8242 being given on Days 1-7 of each 21-day cycle in both the monotherapy and combination therapy arms; data from Arm A will be used to determine whether a participant receives 21-day or 28-day therapy in Arm B.

Trial Description

Primary Outcome:

• Number of participants with dose limiting toxicities (DLTs)
• Number of participants with complete remission (CR) at RP2D
• Number of participants with complete remission with incomplete marrow recovery (CRi) at RP2D

• Number of participants with CR at dose levels other than RP2D
• Number of participants with CRi at dose levels other than RP2D
• Area under the concentration-time curve (AUC) for MK-8242 alone and in combination with cytarabine
• Maximum plasma concentration (Cmax) of MK-8242 alone and in combination with cytarabine
• Time to maximum concentration (Tmax) of MK-8242 alone and in combination with cytarabine
• Accumulation ratio (R) of MK-8242 alone and in combination with cytarabine
• Urine concentration of MK-8242 (Part 2 Arm A only)

View this trial on ClinicalTrials.gov