Clinical Trial: AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase 2 Study of the AKT Kinase Inhibitor MK-2206 in Patients With Relapsed Refractory Acute Myelogenous Leukemia

Brief Summary: This phase II trial is studying how well AKT inhibitor MK-2206 works in treating patients with relapsed or refractory acute myeloid leukemia (AML). AKT inhibitor MK-2206 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the proportion of patients achieving Morphologic Complete Response (CR), Morphologic CR with incomplete count recovery (CRp) or Partial Response (PR) as best response within 3 cycles of therapy with MK-2206.

SECONDARY OBJECTIVES:

I. Describe the disease-free survival of patients that achieve CR/CRp.

II. Determine the toxicity profile of single-agent MK-2206 in this patient population.

III. To determine the biologic effects of MK-2206 on leukemia cells.

OUTLINE:

Patients receive AKT inhibitor MK-2206 orally (PO) once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.


Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Number of Participants With a Response of CR, CRp, or PR [ Time Frame: 12 weeks of treatment ]
    Responses defined by International Working Group (IWG) 2003 Response Criteria: Morphologic Complete Response (CR): Peripheral blood counts: No circulating blasts, Neutrophil count >/= 1.0 x10^9/L, Platelet count >/= 100 x10^9/L; Bone marrow aspirate and biopsy: </= 5% blasts, No detectable Auer rods, No extramedullary leukemia. Partial Response (PR): No circulating blasts, Neutrophil count >/=1.0 x10^9/L, Platelet count >/= 100 x10^9/L, >/= 50 % reduction in bone marrow blast to 6% to 25%, or blasts </= 5% if Auer rods are present. Morphologic CR with incomplete count recovery (CRp): All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L).
  • Treatment-related Non-hematological Toxicity [ Time Frame: Up to 30 days post-treatment ]
    Toxicity assessed using the NIH-NCI Common Terminology Criteria for Adverse Events, version 4.0 (CTCAEv4.0)


Original Primary Outcome: Number of Patients with CR, CRp or PR Response after 3 cycles MK-2206 Therapy [ Time Frame: Following 12 weeks (3 cycles of 28 days) ]

Patient response according to the International Working Group (JCO 2003; 21: 4642-4649): Complete Response (CR), Morphologic CR with incomplete count recovery (CRp), or Partial Response (PR), with or without cytogenetic response.


Current Secondary Outcome: Maximum Percentage Change in Apoptosis [ Time Frame: Baseline to 12 courses ]

Peripheral blood AML cells (total 2 x 10^6) used to determine induction of apoptosis in AML stem cells by 4-color flow cytometry assay (CD34/CD38/CD123/annexin). Two-sample t-test conducted to compare changes between the responders and non-responders. Responders are participants who obtain a CR, CRp, or PR, with or without cytogenetic response.


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: December 1, 2010
Date Started: October 2010
Date Completion:
Last Updated: December 23, 2014
Last Verified: November 2013