MUC1-Targeted Peptide GO-203-2C with or without Decitabine in Treating Patients with Relapsed or Refractory Acute Myeloid Leukemia
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.
- Documented AML by peripheral blood or bone marrow analyses meeting World Health Organization (WHO) criteria, excluding patients with acute promyelocytic leukemia (APL)
- Patients with AML refractory to primary induction chemotherapy, relapsed disease, or age >= 60 and not appropriate for standard cytotoxic therapy due to age, performance status, and/or adverse risk factors according to the treating physician
- Karnofsky performance status >= 50% or Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Life expectancy >= 6 weeks
- Able to understand the investigational nature of this study and to provide written consent to participate in it
- Signed written Institutional Review Board (IRB)-approved informed consent document
- Serum total bilirubin =< 1.5 x institutional upper limit of normal (ULN) OR serum direct bilirubin =< 2 x institutional ULN
- Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) =< 2.5 x institutional ULN
- Serum alkaline phosphatase =< 5 x institutional ULN
- Serum creatinine =< 2.0 mg/dL
- Corrected calcium level >= lower limit of the institutional normal range
- Negative pregnancy test in women of child-bearing potential
- Women and men of child-producing potential must agree to use effective contraceptive methods during the study period (including post-treatment observation period)
- Evidence of leukemic meningitis or other central nervous system (CNS) involvement by leukemia
- Uncontrolled or poorly controlled hypertension (systolic blood pressure [BP] >= 160 mmHg or diastolic BP >= 100 mmHg); Note: an isolated reading that is not sustained will be permitted
- Evidence of New York Heart Association (NYHA) class III or IV cardiac disease, or presence of unstable life-threatening arrhythmia, or history of myocardial infarction during the past 6 months
- Active bacterial, fungal, or viral infection requiring systemic treatment; patients who are receiving treatment for infections that are under control may be included in this study
- Known infection with human immunodeficiency virus (HIV)
- History or major surgery within 4 weeks before the first dose of study treatment, or not recovered from prior surgery
- Exposure to any other investigational agent at any time within 4 weeks before the first dose of study treatment
- Exposure to any other anti-leukemic therapy (except hydroxyurea) within 2 weeks before the first dose of study treatment (including investigational chemotherapy regimens involving approved agents)
- Pregnant or lactating female
- Unwilling or unable to comply with the requirements of the study protocol
Locations & Contacts
Trial Objectives and Outline
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)
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.
Trial Phase & Type
Dana-Farber Harvard Cancer Center
David E. Avigan
Secondary IDs NCI-2014-02034
Clinicaltrials.gov ID NCT02204085