MUC1-Targeted Peptide GO-203-2C with or without Decitabine in Treating Patients with Relapsed or Refractory Acute Myeloid Leukemia

Status: Closed to Accrual

Description

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.

Eligibility Criteria

Inclusion Criteria

  • 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)

Exclusion Criteria

  • 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

See trial information on ClinicalTrials.gov for a list of participating sites.

Trial Objectives and Outline

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.

Trial Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
David E. Avigan

Trial IDs

Primary ID 14-222
Secondary IDs NCI-2014-02034
Clinicaltrials.gov ID NCT02204085