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

NCT01606579 | Completed Phase 1

• 1 other identifier: PRI-724-201
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

Acute Myeloid Leukemia; Chronic Myeloid Leukemia

Keywords

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

Outcome Measures

Primary Outcomes (1)

• DLT (Dose Limiting Toxicity)

  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.

  1 year

Secondary Outcomes (1)

• Preliminary Efficacy Endpoints

  1 year

Study Arms (5)

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.

Drug: 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.

Drug: 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.

Drug: 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.

Drug: 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.

Drug: PRI-724

Interventions

PRI-724 DRUG

PRI-724

Part I; Part II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients 18 years or older
• 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).
• 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).
• 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)
• Performance status 0-2 of the Eastern Cooperative Oncology Group (ECOG) scale
• 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
• 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
• Patients must sign an informed consent indicating that they are aware of the investigational nature of this study.
• 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.

You may not qualify if:

• Patients receiving any other investigational agents
• Patients who are pregnant or breast-feeding
• Known hypersensitivity to any of the components of PRI-724
• Pretreatment QTcF interval \>470 msec (females) or \>450 msec (males)
• Known active hepatitis B, hepatitis C
• 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.
• 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
• Patients on full dose anticoagulants or any dose of warfarin; patients on 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 Part III/Arm B or C of the study.

Sponsors & Collaborators

• Prism Pharma Co., Ltd.: lead
• inVentiv Health Clinical: collaborator

Study Sites (6)

Emory University / Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Massachusetts Medical Center

Worcester, Massachusetts, 01655, United States

Location

New Mexico Cancer Care Alliance

Albuquerque, New Mexico, 87106, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University

Columbus, Ohio, 43210-1267, United States

Location

University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia; Myelodysplastic Syndromes

Interventions

ICG 001

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Jorge Cortes, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2012
• First Posted: May 25, 2012
• Study Start: July 1, 2012
• Primary Completion: December 30, 2016
• Study Completion: December 30, 2016
• Last Updated: August 17, 2017

Record last verified: 2017-05

Locations

US (6)