MDACC Study Summary 2011-0090

Study Summary
No. 2011-0090:.......Leukemia......Srdan Verstovsek......Leukemia

Study Summary Title



Study Summary Number:	2011-0090

Study Title:	A Phase 1/2, Open-label, Dose-escalation, Multi-center Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered NS-018 in Patients with Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis

Physician

New Patient Referral



Name:	Srdan Verstovsek	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:	713-792-7305 Contact us about clinical trials

General Information



Disease Group:	Leukemia	Supported By:	NS Pharma

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

Treatment Agents:	NS-018	Home Care:

Treatment Loc:	Both at MDACC & and Other Sites

Estimated Length of Stay in Houston:


Description/ Intervention:	The goal of this clinical research study is to find the highest tolerable dose of NS-018 that can be given to patients with myelofibrosis. The safety of this drug will also be studied.

Study Objectives / Outcomes

The primary objective of the Phase 1 portion of the study is to evaluate the safety, tolerability, maximum tolerated dose (MTD), and clinically active dose of NS-018 when orally administered in patients with PMF, post-PV MF, or post-ET MF. The secondary objectives of the Phase 1 portion of the study are to determine plasma pharmacokinetics (PK), evaluate pharmacodynamic (PD) correlates, and evaluate preliminary efficacy of NS-018 in patients with PMF, post-PV MF, or post-ET MF.

The primary objective of the Phase 2 portion of the study is to further evaluate the safety and efficacy of the selected dose of NS-018 in patients with PMF, post-PV MF, or post-ET MF. The secondary objectives of the Phase 2 portion of the study are to further determine plasma PK and evaluate PD correlates of NS-018 in patients with PMF, post-PV MF, or post-ET MF.

Study Status Information



Study Activation / Registration Date:

IRB Review and Approval Date:	06/02/2011

Study Type:	Phase I

Recruitment Status:	Open

Projected Accrual:	64

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) Primary myelofibrosis, post-PV MF, or post-ET MF that requires therapy, including patients with intermediate-1, intermediate-2, or high-risk MF according to the International Prognostic Scoring System (IPSS)13, regardless of their JAK2 mutation status. Patients with low-risk MF according to the IPSS can be included if they have symptomatic palpable splenomegaly (at least 5 cm below the left costal margin in the mid-clavicular line by physical examination).

2) You must be at least 18 years old.

3) Eastern Cooperative Oncology Group (ECOG) Performance Status of equal to or less than 2

4) Estimated life expectancy of equal to or more than 12 weeks.

5) Male or non-pregnant, non-lactating female patients. Male and female patients who are fertile and their partners must agree to use one of the following methods of contraception from screening through 90 days following discontinuation of study drug. • Complete abstinence from sexual intercourse • Double-barrier method (condom with spermicide in conjunction with the use of an intrauterine device [IUD] or diaphragm) • Tubal ligation or vasectomy (surgical sterilization)

6) Negative serum or urine pregnancy test within 7 days prior to the first dose of study drug (if patient is a female of childbearing potential)

7) Serum creatinine of equal to or less than 1.5 x the upper limit of normal (ULN) OR estimated creatinine clearance (CrCl) equal to or more than 60 ml/min/1.73 m2 calculated using the Cockcroft and Gault equation: CrCl (mL/min) = [(140-age (years)) x weight (kg)] / (serum creatinine (mg/dL) x 72) For females, multiply result by 0.85

8) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) equal to or less than 3 � the upper limit of normal (ULN) and total bilirubin equal to or less than 1.5 � ULN.

9) Adequate bone marrow reserve, as demonstrated by: • Absolute neutrophil count (ANC) > 1000/�L and • Platelet count > 50,000/�L without the assistance of growth factors.

10) QTcB equal to or less than 480 msec.

11) No MF-directed treatment for at least 2 weeks prior to initiation of NS-018.

12) No treatment with any investigational agent or anticancer agents within 2 weeks prior to initiation of NS-018.

13) Able and willing to refrain from prolonged sun or artificial sunlight exposure (i.e., sunbathing or tanning beds) and able to limit skin and eye exposure to sunlight (i.e., wearing protective clothing, sunscreen, and sunglasses) from first dose of NS-018 to 14 days after discontinuation of NS-018

14) Able to provide written informed consent prior to enrollment into the study

Exclusion Criteria:

1) Active, uncontrolled systemic infection.

2) Patients with any unresolved toxicity (regardless of organs) greater than Grade 1 from previous anticancer therapy.

3) Prior treatment with JAK2 inhibitors that necessitated discontinuation specifically due to gastrointestinal toxicity.

4) Potentially curative therapy is available: • Candidates for hematopoietic stem cell transplant in which transplant is an available and viable option and of higher priority than this study are excluded; • If the patient has declined hematopoietic stem cell transplant, has no donor for transplant, or in the judgment of the investigator is not suitable for transplant, the patient may be enrolled.

5) Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4

6) Patients with a serious cardiac condition within the past 6 months such as uncontrolled arrhythmias, myocardial infarction, angina or heart disease as defined by the New York Heart Association (NYHA) Class III or IV

7) Pregnant or lactating.

8) Radiation therapy for splenomegaly within 6 months prior to study entry (screening).

9) Splenectomy (applicable to patients enrolling in the Phase 2 portion of the study only).

10) Known HIV positive status.

11) Known active hepatitis, a history of viral hepatitis B or hepatitis C, or known positive hepatitis B serologies without a history of immunization.

12) Other concurrent disease and/or medical condition, which, in the judgment of the investigator, would prevent the patient's participation.

13) Patients diagnosed with another malignancy, unless they are disease free. Patients with early stage squamous cell carcinoma of the skin, basal cell carcinoma of the skin, or cervical intraepithelial neoplasia may be eligible for participation at the investigator's discretion.

14) Patients who have had surgery (other than placement of vascular access and bone marrow biopsy) within 4 weeks of study entry (screening), or patients with incomplete recovery from any prior surgical procedures.

15) Patients actively receiving a concurrent investigational agent.

16) Unwilling or unable to comply with the protocol.

Links

Registration Number: NCT01423851
Study Information on Clinical Trials Registry (clinicaltrials.gov)