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

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

  • ORG STUDY ID: PRI-724-201
  • NCT ID: NCT01606579

Conditions

  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia

Interventions

DrugSynonymsArms
PRI-724Part I
PRI-724Part III Arm B
PRI-724Part III Arm A

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

NameTypeDescriptionInterventions
Part IExperimentalSingle-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 IIExperimentalSingle-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 AExperimentalOnce 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 BExperimentalOnce 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 CExperimentalOnce 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:DLT (Dose Limiting Toxicity)
Time Frame:1 year
Safety Issue:
Description:Observance of 1 DLT in first 3 patients during 3+3 phase will result in the enrollment of an additional 3 patients. Observance of 2+ DLTs in 6 patients during 3+3 phase will result in the next lower dose being expanded. Observance of DLTs in 33% of patients in 10 patient MTD expansion will result in the next lower dose being expanded. MTD will only be established in a dose level where 0/3 pts or 1/6 pts have a DLT observed in first 2 cycles of therapy. Two types of DLTs will be observed: non-hematologic and hematologic.

Secondary Outcome Measures

Measure:Preliminary Efficacy Endpoints
Time Frame:1 year
Safety Issue:
Description:The preliminary efficacy endpoints will be changes in the response assessment according to International Working Group Response Criteria for Acute Myeloid Leukemia (AML), European LeukemiaNet Response Criteria for Chronic Myeloid Leukemia (CML), International Working Group Response Criteria for Myelodysplastic Syndromes (MDS) and International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Prism Pharma Co., Ltd.

Trial Keywords

  • Leukemia
  • acute myeloid leukemia
  • AML
  • chronic myeloid leukemia
  • CML
  • MDS
  • myelodysplastic syndrome
  • myeloproliferative neoplasia
  • MPN

Last Updated

August 17, 2017