Study to Determine Safety, Tolerability, Pharmacokinetics, and Activity of K0706 in Healthy Subjects and in Subjects with Chronic Myeloid Leukemia or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

Phase 1

Conditions: Chronic Myeloid Leukemia (CML) or Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
MedDRA version: 19.1 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
MedDRA version: 19.1 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 100000004864
MedDRA version: 19.1 Level: PT Classification code 10034877 Term: Philadelphia chromosome positive System Organ Class: 10022891 - Investigations
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2016-001754-18-CZ

Lead Sponsor: Sun Pharma Advanced Research Company Ltd.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 110

Inclusion Criteria

Subjects may be included if:
1. Willing and able to give written, and dated, informed consent (or legally acceptable representative/impartial witness when applicable) and is available for the entire study
2. Willing and able to comply with the scheduled visits, treatment plan, laboratory testing, study procedures, and restrictions (in the Investigator’s opinion), and be accessible for follow-up
3. Subjects diagnosed with Ph+ CML-CP, Ph+ CML-AP, Ph+ CML-BP, or Ph+ ALL (with at least 1 pathology report within 3 months before Screening) who are refractory or intolerant to at least 3 TKIs or are not eligible (e.g.: due to comorbidities, hypersensitivity to excipients, outside of the US – lack of insurance coverage) for their local country’s regulatory approved and medically appropriate TKIs (e.g.: a TKI that is effective against mutations in the patient’s tumor)
4. Male or female aged = 18 years
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
6. Minimum life expectancy of at least 3 months in the Investigator’s opinion
7. Adequate organ and immune system function as indicated by the following laboratory values obtained = 2 weeks prior to IMP administration:
- ANC = 1000/mm3 applies only to subjects diagnosed with CML-Chronic phase
- Platelets = 50,000/mm3 applies only to subjects diagnosed with CML-Chronic phase
- Serum creatinine = 2.0 mg/dL OR calculated creatinine clearance > 60 mL/min (based on the Cockroft-Gault formula)
- Total bilirubin = 1.5 mg/dL or = 2 mg/dL (for liver metastases)
- AST = 2.5 × upper limit of normal (ULN) or = 5 × ULN (for liver metastases)
- ALT = 2.5 × ULN or = 5 × ULN (for liver metastases)
- Alkaline phosphatase = 5 × ULN (unless bone metastases are present)
- Prothrombin time < 1.5 × ULN
8. Subjects of childbearing potential must practice an acceptable method of birth control as judged by the Investigator:
a. Medically acceptable methods of birth control include the use of either a contraceptive implant or a contraceptive injection (e.g., Depo-Provera™) or an IUD, same sex partner, a vasectomized partner, or an oral contraceptive taken continually within the past 3 months and the subject has to agree to continued use during the study
b. To adopt another birth control method, or a double-barrier method which consists of a combination of any 2 of the following: diaphragm, cervical cap, condom, or a spermicide at least 2 months prior to study entry and must continue to use contraception for the duration of the study
c. Subjects who are postmenopausal for at least 1 year as per Investigator’s discretion or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy has been performed on the subject)
9. Male subjects enrolled in the study should not father a child and are advised to prevent passage of semen to their sexual partner during intercourse using an acceptable method as detailed in the protocol and judged by the Investigator for the duration of the study and for 3 months after the last IMP administration
10. Female subjects of childbearing potential must have a negative serum pregnancy test

Exclusion Criteria

Subjects will be excluded from the study if:
1. Any major surgery, as determined by the Investigator, within 4 weeks of IMP administration
2. Inability to swallow oral medication
3. Inability to undergo venipuncture and/or tolerate venous access
4. Evidence of organ dysfunction or any clinically relevant deviation from normal in physical examination, ECG findings, vital signs, or clinical laboratory test findings as per the Investigator’s discretion
5. Positive exclusion tests: urine pregnancy tests (if applicable), HIV, hepatitis B surface antigen, or hepatitis C virus
6. History of any relevant allergy/hypersensitivity (including known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the IMP or its excipients)
7. Received an investigational agent within 30 days (or for investigational agents with long half-life a washout of 5 half-lives will be required) of IMP administration or intake of an investigational drug during the course of this study
8. Sensitive substrates of CYP2C8 with a narrow therapeutic index, along with strong inhibitors or inducers of major CYP enzymes, should be avoided or used with caution in this trial
9. Use of concomitant medication that might reasonably influence the results of the study prior to IMP administration and at any time during the study
10. Known or suspected history of significant drug abuse as judged by the Investigator
11. History of alcohol abuse or excessive intake of alcohol, defined as regular weekly intake of more than 8 units of alcohol in females or 15 units of alcohol in males (Note: 1 unit equals 25 mL spirits, 125 mL wine, or 250 mL beer or lager) in the 12 months prior to study entry
12. Inability or unwillingness to comply with study procedures, restrictions, and requirements, as judged by the Investigator
13. Involvement in the planning and/or conduct of the study (applies to Sponsor, Contract Research Organizations, and study center staff, etc.)
14. Had cytotoxic chemotherapy or radiotherapy within 21 days (or 42 days for nitrosoureas or mitomycin C) or targeted therapy such as but not limited to BCR-ABL Tyrosine Kinase Inhibitors = 14 days prior to the first IMP administration visit, or those who have not recovered (greater than Grade 1 by NCI CTCAE v4.03) from AEs due to agents administered more than 28 days earlier than the first IMP administration visit, with the exception of alopecia
15. Malabsorption syndrome or other illness that could affect oral absorption of the IMP
16. History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
17. Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
a. Uncontrolled hypertension (diastolic blood pressure > 85 mmHg; systolic blood pressure > 145 mmHg)
b. Recent (< 1 year) history of myocardial infarction (MI), unstable angina, coronary heart disease, cerebrovascular accident, or transient ischemic attack (TIA)
c. Congestive heart failure (New York Heart Association [NYHA] Class III or IV) within 6 months prior to enrollment, or left ventricular ejection fraction (LV

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method