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A Phase I/II Trial of the MUC1 Inhibitor, GO-203-2C in Patients With Relapsed or Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT02204085
Recruitment Status : Recruiting
First Posted : July 30, 2014
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
David Avigan, MD, Beth Israel Deaconess Medical Center

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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia, in Relapse Recurrent Adult Acute Myeloid Leukemia Drug: GO-203-2c Drug: GO-203-2c + Decitabine Phase 1 Phase 2

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 53 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of the MUC1 Inhibitor, GO-203-2C in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Study Start Date : September 2014
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : July 2021


Arm Intervention/treatment
Experimental: GO-203-2c

Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.

GO-203-2c given daily on predetermined schedule of a 28-day treatment cycle

Drug: GO-203-2c
Experimental: GO-203-2c + Decitabine

Dose escalation will occur for GO-203-2c using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation.

GO-203-2c given daily on predetermined schedule of a 28-day treatment cycle. Decitabine will be administered at a dose of 20mg/m2 on days 8-12 of a 28-day treatment cycle.

Drug: GO-203-2c
Drug: GO-203-2c + Decitabine



Primary Outcome Measures :
  1. Maximum Tolerated Dose of GO-203-2c [ Time Frame: 28 days ]
    Phase I

  2. Maximum Tolerated Dose of GO-203-2c in combination with decitabine [ Time Frame: 28 days ]
    Phase 1


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 2 years ]
  2. 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 [ Time Frame: 2 Years ]
  3. To assess whether in vitro response to GO-203-2c alone and in combination with decitabine is associated with clinical response [ Time Frame: 2 Years ]
  4. 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 [ Time Frame: 2 Years ]
  5. To determine if therapy GO-203-2c in combination with decitabine results in at least 20% of patients achieving a clinical response [ Time Frame: 2 years ]
    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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02204085


Contacts
Contact: David Avigan, MD 617-667-9920 davigan@bidmc.harvard.edu
Contact: Emma Logan 617-667-5984 eklogan@bidmc.harvard.edu

Locations
United States, Massachusetts
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Richard M. Stone, MD    617-632-2214    rstone@partners.org   
Principal Investigator: Richard Stone, MD         
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: David Avigan, MD    617-667-9920    davigan@bidmc.harvard.edu   
Principal Investigator: David Avigan, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Investigators
Principal Investigator: David Avigan, MD Beth Israel Deaconess Medical Center

Responsible Party: David Avigan, MD, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT02204085     History of Changes
Other Study ID Numbers: 14-222
First Posted: July 30, 2014    Key Record Dates
Last Update Posted: August 24, 2018
Last Verified: August 2018

Keywords provided by David Avigan, MD, Beth Israel Deaconess Medical Center:
Refractory acute myeloid leukemia
Relapsed acute myeloid leukemia

Additional relevant MeSH terms:
Leukemia, Myeloid, Acute
Leukemia
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors