Clinical trial NCT02204085: A Phase I/II Trial of the MUC1 Inhibitor, GO-203-2C in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Official title: A Phase I/II Trial of the MUC1 Inhibitor, GO-203-2C in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia, in Relapse
Recurrent Adult Acute Myeloid Leukemia
Keywords: Refractory acute myeloid leukemia
Relapsed acute myeloid leukemia
Lead sponsor: Beth Israel Deaconess Medical Center
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2014-07-30
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This research study is studying a targeted therapy known as GO-203-2C as a possible treatment for with acute myeloid leukemia (AML) both alone and in combination with decitabine. GO-203-2c targets cancer cells, while leaving healthy cells unaffected.This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of an investigational intervention and also tries to define the appropriate dose of the investigational intervention to use for further studies.

Detailed description: * Phase I

  * The maximum tolerated dose (MTD) will be determined in the phase I section of the trial.
  * Patients who fulfill eligibility criteria will be entered into the trial to GO-203-2c.
  * After the screening procedures confirm participation in the research study. The investigators are looking for the highest dose of the combination of study drugs that can be administered safely without severe or unmanageable side effects in participants that have acute myeloid leukemia (AML) not everyone who participates in this research study will receive the same dose of the study drug. The dose given will depend on the number of participants who have been enrolled in the study prior and how well the dose was tolerated.
  * A subsequent dose escalation will evaluate the combination of GO-203-2c and decitabine.
* Phase II

  * The primary goal is to determine if the combination of the two drugs results in clinical response

Eligibility criteria: Inclusion Criteria:

* To be considered eligible for enrollment into this study, all of the following inclusion criteria must be met during the screening period:
* Documented AML by peripheral blood and bone marrow analyses meeting 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
* Age ≥ 18 years
* Karnofsky performance status ≥ 50% or 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 IRB-approved Informed Consent document
* Adequate hepatic and renal function:

  * serum bilirubin ≤ 1.5 X institutional ULN OR serum direct bilirubin ≤ 2 X institutional ULN
  * serum ALT and AST ≤ 2.5 X institutional ULN
  * serum alkaline phosphatase \< 5 X institutional ULN
  * serum creatinine ≤ 2.0 mg/dL
  * corrected calcium level ≥ institutional LLN
* 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:

* A patient will be considered not eligible for enrollment into this study if any of the following criteria are met during the screening period:
* Evidence of leukemic meningitis or other CNS involvement by leukemia
* Uncontrolled or poorly controlled hypertension (systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg) Note: an isolated reading that is not sustained will be permitted.
* Evidence of 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
* Known infection with 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, see Section 5.5.1) within 2 weeks before the first dose of study treatment
* Pregnant or lactating female
* Unwilling or unable to comply with the requirements of the study protocol

Primary outcomes:
measure: Maximum Tolerated Dose of GO-203-2c
timeFrame: 28 days
measure: Maximum Tolerated Dose of GO-203-2c in combination with decitabine
timeFrame: 28 days
Secondary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: 2 years
measure: To investigate whether GO-203-2c alone and in combination with decitabine is effective in targeting MUC1-C overexpressing AML progenitor cells in the lab
timeFrame: 2 Years
measure: To assess whether in vitro response to GO-203-2c alone and in combination with decitabine is associated with clinical response
timeFrame: 2 Years
measure: 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 NSG mouse model
timeFrame: 2 Years
measure: To determine if therapy GO-203-2c in combination with decitabine results in at least 20% of patients achieving a clinical response
timeFrame: 2 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
Study officials:
affiliation: Beth Israel Deaconess Medical Center
name: David Avigan, MD
role: PRINCIPAL_INVESTIGATOR
References: