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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Prism Pharma Co., Ltd.
Sponsor:
Collaborator:
inVentiv Health Clinical
Information provided by (Responsible Party):
Prism Pharma Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01606579
First received: May 16, 2012
Last updated: April 28, 2014
Last verified: April 2014
  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).


Condition Intervention Phase
Acute Myeloid Leukemia
Chronic Myeloid Leukemia
Drug: PRI-724
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Dose-Escalation Phase I/II Study of PRI-724 for Patients With Advanced Myeloid Malignancies

Resource links provided by NLM:


Further study details as provided by Prism Pharma Co., Ltd.:

Primary Outcome Measures:
  • DLT (Dose Limiting Toxicity) [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

    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:
  • Preliminary Efficacy Endpoints [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 104
Study Start Date: July 2012
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part I
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.
Drug: PRI-724
PRI-724
Experimental: Part II
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.
Drug: PRI-724
PRI-724
Experimental: Part III Arm A

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.

Drug: PRI-724
PRI-724 in combination with low dose ara-C therapy
Experimental: Part III Arm B

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.

Drug: PRI-724
PRI-724 in combination with dasatinib
Experimental: Part III Arm C

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.

Drug: PRI-724
PRI-724 in combination with dasatinib

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01606579

Contacts
Contact: Andria E Cress, BA (773) 632-1750 andria.cress@inventivhealth.com
Contact: Craig Schleyer (773)632-1785 craig.schleyer@inventivhealth.com

Locations
United States, Texas
University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Jorge Cortes, MD    713-794-5783    jcortes@mdanderson.org   
Contact: Alfonso Quintas Cardama, MD    (713) 745-4009    aquintas@mdanderson.org   
Principal Investigator: Jorge Cortes, MD         
Sub-Investigator: Alfonso Quintás Cardama, MD         
Sponsors and Collaborators
Prism Pharma Co., Ltd.
inVentiv Health Clinical
Investigators
Principal Investigator: Jorge Cortes, MD M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: Prism Pharma Co., Ltd.
ClinicalTrials.gov Identifier: NCT01606579     History of Changes
Other Study ID Numbers: PRI-724-201
Study First Received: May 16, 2012
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Prism Pharma Co., Ltd.:
Leukemia
acute myeloid leukemia
AML
chronic myeloid leukemia
CML
MDS
myelodysplastic syndrome
myeloproliferative neoplasia
MPN

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases

ClinicalTrials.gov processed this record on August 28, 2014