Clinical Trials /

Safety and Efficacy Study of PRI-724 in Subjects With Advanced Myeloid Malignancies

NCT01606579

Description:

PRI-724 is a new investigational drug being studied to treat subjects with cancer who have advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling pathway that cancer cells need to grow and spread (metastasize).

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Safety and Efficacy Study of PRI-724 in Subjects With Advanced Myeloid Malignancies

Title

  • Brief Title: Safety and Efficacy Study of PRI-724 in Subjects With Advanced Myeloid Malignancies
  • Official Title: An Open-Label, Dose-Escalation Phase I/II Study of PRI-724 for Patients With Advanced Myeloid Malignancies
  • Clinical Trial IDs

    NCT ID: NCT01606579

    ORG ID: PRI-724-201

    Trial Conditions

    Acute Myeloid Leukemia

    Chronic Myeloid Leukemia

    Trial Interventions

    Drug Synonyms Arms
    PRI-724 Part I, Part II
    PRI-724 Part III Arm B, Part III Arm C
    PRI-724 Part III Arm A

    Trial Purpose

    PRI-724 is a new investigational drug being studied to treat subjects with cancer who have
    advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling
    pathway that cancer cells need to grow and spread (metastasize).

    Detailed Description

    PRI-724 is a new investigational drug being studied to treat subjects with cancer who have
    advanced myeloid malignancies. PRI-724 is thought to work by blocking the Wnt signaling
    pathway that cancer cells need to grow and spread (metastasize).

    Purpose:

    - To test the safety of PRI-724 when taken intravenously (through the vein).

    - To observe whether PRI-724 can slow or stop the progression of leukemia.

    - To find the Maximum Tolerated Dose (highest safe dose) in the first two parts of the
    study.

    - To find the dose of PRI-724 that should be used in the third part of the study and
    possible future clinical trials that will study effectiveness and additional safety.

    - To test the safety of combining PRI-724 with an approved cancer drug called dasatinib
    in treating chronic myeloid leukemia (CML).

    - To evaluate whether the combination of PRI-724 with the approved cancer drug dasatinib
    slows or stops the progression of chronic myeloid leukemia (CML).

    - To test the safety of combining PRI-724 with an approved cancer drug called Cytarabine
    in treating acute myelogenous leukemia (AML).

    - To evaluate whether the combination of PRI-724 with the approved cancer drug Cytarabine
    slows or stops the progression of acute myelogenous leukemia (AML).

    - To measure how much PRI-724 appears and remains in the blood after infusion.

    - To measure several signals called biomarkers associated with cancer in the blood to see
    if PRI-724 affects those signals.

    Study Design:

    This will be a single center, open-label escalating-dose cohort study with 3 parts: Part I
    during which the MTD will be determined in acute group patients; Part II during which the
    MTD will be determined in non-acute group patients; and Part III during which safety and
    tolerability of escalating doses of PRI-724 will be assessed in combination with dasatinib
    for CML patients or low dose ara-C therapy for AML patients 65 years of age.

    Trial Arms

    Name Type Description Interventions
    Part I Experimental Single-agent MTD (or maximum dose to be studied) of PRI-724 will be determined in escalating dose cohorts of Acute Group patients. The MTD cohort will be expanded up to 10 patients to further evaluate tolerability. PRI-724
    Part II Experimental Single-agent MTD (or maximum dose to be studied) of PRI-724 will be determined in escalating dose cohorts of Non-Acute Group patients. Dosing will begin 2 dose levels below the Part I MTD. The MTD cohort will be expanded up to 10 patients to further evaluate tolerability. PRI-724
    Part III Arm A Experimental Once the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each. Escalating doses of PRI-724, beginning 2 dose levels below the Part I MTD will be administered in combination with low dose ara-C therapy (20 mg SC BID 10d q 28d) for AML patients 65 years of age. PRI-724
    Part III Arm B Experimental Once the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each. Escalating doses of PRI-724, beginning 2 dose levels below the Part I MTD will be administered in combination with dasatinib (140 mg PO daily) to Acute Group patients with CML-AP or BC. PRI-724
    Part III Arm C Experimental Once the MTD is identified for each arm, that cohort will be expanded to a total of 10 patients each. Escalating doses of PRI-724, beginning 1 dose level below the Part II MTD will be administered in combination with dasatinib (100 mg PO daily) to Non-Acute Group patients with CML-CP. PRI-724

    Eligibility Criteria

    Inclusion Criteria

    1. Patients 18 years or older

    2. Part I: Patients with one of the following histologically- or cytologically-proven
    conditions: relapsed/refractory AML, relapsed/refractory MDS, or advanced CML in AP
    or BP (i.e., Acute Group patients).

    3. Part II: Patients with one of the following documented conditions: CML in CP that
    is Philadelphia chromosome (Ph)-positive (by cytogenetics) or BCR-ABL1-positive by
    fluorescent in situ hybridization [FISH], or PCR), as well as resistant to at least 2
    FDA-approved tyrosine kinase inhibitors (TKIs); or a myeloproliferative neoplasia
    which includes: PMF and myelofibrosis secondary to polycythemia vera (PV) and
    essential thrombocythemia (ET) myelofibrosis (MF) (with intermediate-1,
    intermediate-2 or high risk disease according to the International Working Group
    [IWG] prognostic scoring system) (i.e., Non-Acute Group patients).

    4. Part III:

    - Arm A: Patients with AML who are 65 years of age or older with refractory or
    relapsed disease, or who have not received prior therapy but are not eligible to
    receive intensive frontline chemotherapy (i.e., Acute Group patients);

    - Arm B: Patients with CML in AP or BP, either newly diagnosed or failing TKI
    therapy (i.e., Acute Group patients);

    - Arm C: Patients with CML in CP after failure of 2 FDA-approved TKIs (i.e.,
    Non-Acute group patients)

    5. Performance status 0-2 of the Eastern Cooperative Oncology Group (ECOG) scale

    6. Patients must have been off all prior therapy for leukemia except hydroxyurea for 1
    week prior to entering this study and recovered from the toxic effects of that
    therapy

    7. Adequate organ function as defined by:

    - Serum creatinine 2.0 mg/dL or calculated creatinine clearance 60 mL/min

    - Total bilirubin 2 x ULN (5 x ULN if considered due to Gilbert's syndrome or
    hemolysis)

    - Alanine aminotransferase (ALT) 3xULN

    8. Patients must sign an informed consent indicating that they are aware of the
    investigational nature of this study.

    9. Women of childbearing potential and men should practice effective methods of
    contraception. Women of childbearing potential should have a negative urine or serum
    pregnancy test (minimum sensitivity 25 IU/L or equivalent units of human chorionic
    gonadotropin within 7 days prior to the start of PRI 724.

    Exclusion Criteria

    1. Patients receiving any other investigational agents

    2. Patients who are pregnant or breast-feeding

    3. Known hypersensitivity to any of the components of PRI-724

    4. Pretreatment QTcF interval >470 msec (females) or >450 msec (males)

    5. Known active hepatitis B, hepatitis C

    6. Serious uncontrolled medical disorder or active systemic infection or current
    unstable or decompensated medical condition, which makes it undesirable or unsafe for
    the patient to participate in the study including: New York Heart Association (NYHA)
    Class 3 or 4, myocardial infarction within 3 months, uncontrolled angina within 3
    months, history of clinically significant ventricular arrhythmia, diabetes mellitus
    with ketoacidosis, or chronic obstructive pulmonary disease (COPD) requiring
    hospitalization in 6 months prior to the start of treatment with PRI-724.

    7. Any other condition, including mental illness or substance abuse deemed by the
    Investigator to be likely to interfere with a patient's ability to sign informed
    consent, cooperate, and participate in the study

    8. Patients on full dose anticoagulants or any dose of warfarin; patients on
    prophylactic dose of low-molecular weight or unfractionated heparin are allowed.

    9. Patients who have demonstrated intolerance to dasatinib 100 mg daily will not be
    eligible for Part III/Arm B or C of the study.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    DLT (Dose Limiting Toxicity)

    Secondary Outcome Measures

    Preliminary Efficacy Endpoints

    Trial Keywords

    Leukemia

    acute myeloid leukemia

    AML

    chronic myeloid leukemia

    CML

    MDS

    myelodysplastic syndrome

    myeloproliferative neoplasia

    MPN