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: 20.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
MedDRA version: 20.0 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 100000004864
MedDRA version: 20.1 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-ES

Lead Sponsor: Sun Pharma Advanced Research Company (SPARC) Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 89

Inclusion Criteria

Part C:
1.Willing and able to give written/signed, and dated, informed consent (or by 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, and be accessible for follow-up
3.Subjects with CML in any phase or Ph+ ALL who are resistant and/or intolerant to = 3 prior TKIs or are not eligible for 3rd TKI [e.g.: due to comorbidities, hypersensitivity to excipients, resistance/intolerance to at least 2 TKIs other than imatinib) or the TKIs are ineffective against mutations detected 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.Adequate organ and immune system function as indicated by the following laboratory values obtained = 2 weeks prior to IMP administration.
7.Subjects of childbearing potential must practice a medically acceptable method of birth control as judged by the Investigator (refer to protocol for details)
8.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 Inclusion criteria # 7 and judged by the Investigator for the duration of the study and for 3 months after the last IMP administration
9.Female subjects of childbearing potential must have a negative pregnancy test (as confirmed by a negative urine pregnancy test with a sensitivity of less than 50 mIU/mL or equivalent units of human chorionic gonadotropin).
10.Female subjects should be non-lactating and non-breast-feeding
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 42
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 41

Exclusion Criteria

Part C:
1.Presence of T315I mutations
2.Any major surgery, as determined by the Investigator, within 14 days of IMP administration
3.Inability to swallow oral medication
4.Evidence of clinically significant organ dysfunction or any clinically relevant deviation from normal in physical examination, ECG findings, vital signs, or clinical laboratory test findings which in the opinion of the investigator may jeopardize the safety of the patient during the study or may interfere with the evaluation of the study medication.
5.Positive exclusion tests: urine pregnancy tests (if applicable), HIV
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.Known history of active hepatitis B or hepatitis C
8.Received an investigational agent within 30 days of IMP administration
9.Subjects on sensitive substrates of CYP2C8 with a narrow therapeutic index, or on strong inhibitors or inducers of major CYP enzymes, should be avoided or used with caution in this trial
10.Use of concomitant medication that might influence the results of the study prior to IMP administration/or anticipated need any time during the study
11.Known or suspected history of significant drug or alcohol abuse as judged by the Investigator
12.Radiotherapy within 21 days or cytotoxic chemotherapy or Vincristine within 7 days (for Ph+ ALL only); interferon or Cytarabine or immunotherapy within 14 days prior to the first IMP administration visit
13.Active central nervous system (CNS) disease as evidenced by cytology or pathology.
14.Malabsorption syndrome or other illness that could affect oral absorption of the IMP
15.Clinically significant, uncontrolled, or active cardiovascular disease
16.Uncontrolled intercurrent illness
17.Subjects eligible and willing to undergo bone marrow transplant
18.Autologous or allogeneic stem cell transplant = 3 months prior to Screening
19.Another primary malignancy within the past 3 years or earlier.
20.Any contraindications for repeated bone marrow sample collection
21.Prior exposure to K0706 therapy as a participant in Part B of the protocol

Other criteria may apply (refer to protocol)

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

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