MDACC Study Summary 2011-0527

Study Summary
No. 2011-0527:.......Leukemia......Jorge Cortes......Leukemia

Study Summary Title



Study Summary Number:	2011-0527

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

Physician

New Patient Referral



Name:	Jorge Cortes	Patients Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Dept:	Leukemia	Referring MD Call:	800-392-1611 (in U.S.A.) 713-792-6161 (outside U.S.A.)

Phone:	713-794-5783 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	PRISM BioLab Corporation

Phase of Study:	Phase I/Phase II	Return Visit:

Treatment Agents:	PRI-724	Home Care:

Treatment Loc:	Only at MDACC

Estimated Length of Stay in Houston:

Description/
Intervention:

The goal of Phase I of this clinical research study is to learn the highest
tolerable dose of PRI-724 that can be given to patients with advanced myeloid
cancer.

In Phase II, researchers will study the safety of PRI-724 combined with a
standard drug, dasatinib or cytarabine. Researchers also want to learn if
PRI-724 combined with dasatinib can help to control CML, and if PRI-724
combined with cytarabine can help control AML.

PRI-724 is designed to keep cancer cells from sending and receiving signals
that they need to grow and spread.

Study Objectives / Outcomes

Primary Objectives

To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of PRI-724 when administered as a 7-day intravenous (IV) infusion to patients with advanced myeloid malignancies.

To determine the pharmacokinetics of PRI-724 when administered as a 7-day IV infusion to patients with advanced myeloid malignancies.

To assess the safety of PRI-724 when given as a continuous 7-day IV infusion to patients with advanced myeloid malignancies.

Secondary Objectives

To describe the efficacy of PRI-724 when given as a 7-day IV infusion to patients with advanced myeloid malignancies in the MTD expansion phase of the study.

To assess the safety and efficacy of PRI-724 in combination with dasatinib in patients with chronic myeloid leukemia (CML) or in combination with low dose ara-C in patients with acute myeloid leukemia (AML) 65 years of age or older (Phase II of the study).

To determine the pharmacodynamic effects of PRI-724 on leukemic cells prior to and after treatment and their correlation with response.

Exploratory Objective

To assess mRNA expression of survivin by reverse transcriptase-polymerase chain reaction (RT-PCR) in peripheral blood and/or marrow leukemic cells obtained from patients prior to and after PRI-724 therapy.

Study Status Information



Study Activation / Registration Date:	07/17/2012

IRB Review and Approval Date:	07/17/2012

Study Type:	Phase Ii Or Phase I/Ii

Recruitment Status:	Open

Projected Accrual:	N/A

Enrollment Eligibility

If you do not meet the enrollment eligibility, there may be other treatment options for you. Please Contact the Referral Office for more information.

Inclusion Criteria:

1) Patients 18 years or older with Philadelphia chromosome (Ph)-positive or BCR-ABL1-positive CML (as determined by cytogenetics, fluorescent in situ hybridization [FISH], or polymerase chain reaction [PCR]) in CP resistant to at least 2 of the 3 FDA-approved TKIs (i.e., imatinib, nilotinib, dasatinib) or in AP or 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 therapy

4) Adequate organ function: a) serum creatinine </=2.0 mg/dl or calculated creatinine clearance >/=60 mL/min; b) Total bilirubin </=2xULN (</=5xULN if considered due to Gilbert's syndrome or hemolysis); c) alanine aminotransferase (ALT) </=3xULN

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 [HCG]) 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 two 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:

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 heparin are allowed.

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

Links

Registration Number: NCT01606579
Study Information on Clinical Trials Registry (clinicaltrials.gov)