AKT Inhibitor MK-2206 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
|Adult Acute Megakaryoblastic Leukemia (M7) Adult Acute Minimally Differentiated Myeloid Leukemia (M0) Adult Acute Monoblastic Leukemia (M5a) Adult Acute Monocytic Leukemia (M5b) Adult Acute Myeloblastic Leukemia With Maturation (M2) Adult Acute Myeloblastic Leukemia Without Maturation (M1) Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Adult Acute Myeloid Leukemia With Del(5q) Adult Acute Myeloid Leukemia With Inv(16)(p13;q22) Adult Acute Myeloid Leukemia With t(16;16)(p13;q22) Adult Acute Myeloid Leukemia With t(8;21)(q22;q22) Adult Acute Myelomonocytic Leukemia (M4) Adult Erythroleukemia (M6a) Adult Pure Erythroid Leukemia (M6b) Recurrent Adult Acute Myeloid Leukemia||Drug: Akt inhibitor MK2206 Other: laboratory biomarker analysis||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 2 Study of the AKT Kinase Inhibitor MK-2206 in Patients With Relapsed Refractory Acute Myelogenous Leukemia|
- 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)
- 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.
|Study Start Date:||October 2010|
|Study Completion Date:||April 2014|
|Primary Completion Date:||October 2013 (Final data collection date for primary outcome measure)|
Experimental: Treatment (Akt inhibitor MK2206)
Akt inhibitor MK2206 200 mg orally once a week for each 28 day treatment cycle
Drug: Akt inhibitor MK2206
200 mg orally (PO) once weekly. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Other Name: MK2206Other: laboratory biomarker analysis
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01253447
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Washington|
|Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium|
|Seattle, Washington, United States, 98109|
|Principal Investigator:||Marina Konopleva, MD, PHD||UT MD Anderson Cancer Center|