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An Open-Label, Dose-Escalation Phase I/II Study of PRI-724 for Patients With Advanced Myeloid Malignancies

Phase 1/Phase 2
18 Years
Open (Enrolling)
Acute Myeloid Leukemia, Chronic Myeloid Leukemia

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Trial Information

An Open-Label, Dose-Escalation Phase I/II Study of PRI-724 for Patients With Advanced Myeloid Malignancies

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).


- 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 part of the study.

- To find the dose of PRI-724 that should be used in the second 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: Phase Ia
during which the MTD will be determined; Phase Ib expansion phase during which the
tolerability of the MTD will be further defined; and Phase II 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

Inclusion Criteria:

Patients must fulfill all of the following criteria:

1. Patients 18 years or older with Philadelphia chromosome (Ph)-positive or break point
cluster region BCR ABL1 positive CML (as determined by cytogenetics, fluorescent in
situ hybridization [FISH], or PCR) in CP-resistant to at least 2 of the 3
FDA-approved tyrosine kinase inhibitors (TKIs) (i.e., imatinib, nilotinib, dasatinib)
or in accelerated phase (AP) or blast phase (BP) (either newly diagnosed or
TKI-resistant), relapsed/refractory MDS, AML, or PMF, Post-polycythemia vera (PV) or
Post-essential thrombocythemia (ET) myelofibrosis (with intermediate-1, intermediate
-2 or high risk disease according to the International Working Group [IWG] prognostic
scoring system)

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

3. 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

4. Adequate organ function as defined by:

- serum creatinine ≤2.0 mg/dL or calculated creatinine clearance ≥60 mL/min

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

- alanine aminotransferase (ALT) ≤3x ULN

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

6. 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.

7. 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, are eligible for the Phase II portion of the study.

8. Patients with CML-CP after failure of 2 FDA-approved TKIs (i.e., imatinib, nilotinib,
dasatinib) or patients with CML in AP or BP either newly diagnosed or failing TKI
therapy will be eligible to enroll in the Phase II study for patients with CML.

Exclusion Criteria:

Patients exhibiting any of the following will be excluded from the trial:

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 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 a
prophylactic dose of low-molecular weight or unfractionated heparin are allowed.

Patients who have demonstrated intolerance to dasatinib 100 mg daily will not be eligible
for the Phase II portion of the study.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

DLT (Dose Limiting Toxicity)

Outcome 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.

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Jorge Cortes, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

July 2012

Completion Date:

February 2014

Related Keywords:

  • Acute Myeloid Leukemia
  • Chronic Myeloid Leukemia
  • Leukemia
  • acute myeloid leukemia
  • AML
  • chronic myeloid leukemia
  • CML
  • MDS
  • myelodysplastic syndrome
  • myeloproliferative neoplasia
  • MPN
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive



University of Texas M.D. Anderson Cancer Center Houston, Texas  77030