This phase I/II trial studies the side effects and best dose of mucin 1 (MUC1)-targeted peptide GO-203-2C and to see how well it works when given alone or together with decitabine in treating patients with acute myeloid leukemia that has returned after a period of improvement or does not respond to treatment. Drugs used in chemotherapy, such as MUC1-targeted peptide GO-203-2C and decitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02204085.
PRIMARY OBJECTIVES:
I. To estimate the maximal tolerated dose (MTD) of GO-203-2c (MUC1-targeted peptide GO-203-2C), given on days 1-5 + 8-12 + 15-19 of a 28-day treatment cycle, in a refractory/relapsed acute myeloid leukemia (AML) study population. (Phase I)
II. To evaluate the maximal tolerated dose (MTD) of GO-203-2c given on days 1-5 and 8-12 in combination with decitabine 20 mg/m^2 administered on days 8-12 of a 28 days treatment cycle. (Phase I)
III. To determine if therapy GO-203-2c in combination with decitabine results in at least 20% of patients achieving a clinical response (blast response, minor response, partial response, or complete response). (Phase II)
SECONDARY OBJECTIVES:
I. To investigate the safety and dose limiting toxicities (DLTs) of GO-203-2c in the study population.
II. To investigate the safety and dose limiting toxicities (DLTs) of GO-203-2c in combination with decitabine in the study population.
III. To investigate whether GO-203-2c alone and in combination with decitabine is effective in targeting MUC1-C overexpressing AML progenitor cells.
IV. To assess whether in vitro response to GO-203-2c alone and in combination with decitabine as manifested by effect on (i) reactive oxygen species (ROS) (hydrogen peroxide, superoxide) levels, (ii) glutathione (GSH) levels, (iii) survivin expression (reverse transcription-polymerase chain reaction [RT-PCR] and immunoblot [IB]), and (iv) growth and survival is associated with clinical response.
V. To determine if therapy with GO-203-2c alone and in combination with decitabine results in decreased engraftment potential of AML progenitor cells in an NOD scid gamma (NSG) mouse model.
OUTLINE: This is a phase I, dose-escalation study of GO-203-2C followed by a phase II study. Patients are assigned to 1 of 2 arms.
ARM I: Patients receive MUC1-targeted peptide GO-203-2C intravenously (IV) over 60 minutes on days 1-5, 8-12, and 15-19. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
ARM II: Patients receive MUC1-targeted peptide GO-203-2C IV over 60 minutes on days 1-5 and 8-12, and decitabine IV over 60 minutes on days 8-12. Courses repeat every 35 days in the absence of disease progression or unacceptable toxicity. After 1 year of treatment, patients have the option to continue to receive MUC1-targeted peptide GO-203-2C and decitabine on days 1-5 and 8-12 every 35-56 days at the discretion of the treating physician.
After completion of study treatment, patients are followed up for 30 days and then every 3 months thereafter.
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorDavid E. Avigan
