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: 20.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864
MedDRA version: 20.0Level: LLTClassification code 10009015Term: Chronic myeloid leukemiaSystem Organ Class: 100000004864
MedDRA version: 20.1Level: PTClassification code 10034877Term: Philadelphia chromosome positiveSystem Organ Class: 10022891 - Investigations
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2016-001754-18-PL

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

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 255

Inclusion Criteria

Part B:
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 diagnosed with Ph+ CML-CP, Ph+ CML-AP, Ph+ CML-BP, or Ph+ ALL who are refractory or intolerant to at least 3 TKIs or are not eligible (e.g.: due to comorbidities, hypersensitivity to excipients, 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.Adequate organ and immune system function as indicated by the 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

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-b

Exclusion Criteria

Part B:
1.Presence of T315I mutations
2.Any major surgery, as determined by the Investigator, within 4 weeks of IMP administration
3.Inability to swallow oral medication
4.Inability to undergo venipuncture and/or tolerate venous access
5.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 drug
6.Positive exclusion tests: urine pregnancy tests (if applicable), HIV
7.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)
8.Known history of active hepatitis B or hepatitis C
9.Received an investigational agent within 30 days of IMP administration
10.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
11.Use of concomitant medication that might influence the results of the study prior to IMP administration and/or anticipated need at any time during the study
12.Known or suspected history of significant drug abuse, of alcohol abuse or excessive intake of alcohol in the 12 months prior to study entry
13.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 Malabsorption syndrome or other illness that could affect oral absorption of the IMP
14.History of acute pancreatitis within 1 year of study or history of chronic pancreatitis
15.Clinically significant, uncontrolled, or active cardiovascular disease
16.Uncontrolled intercurrent illness including
17.Subjects eligible and willing to undergo transplant
18.Autologous or allogeneic stem cell transplant = 3 months prior to Screening

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.Radiotherap

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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