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: 21.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864
MedDRA version: 21.1Level: LLTClassification code 10009015Term: Chronic myeloid leukemiaSystem Organ Class: 100000004864
MedDRA version: 21.0Level: PTClassification code 10034877Term: Philadelphia chromosome positiveSystem Organ Class: 10022891 - Investigations
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2016-001754-18-BE

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 - inclusion of subjects needing legally acceptable representative/impartial witness will be in compliance to the enrolling country’s regulatory requirement) 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 must 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- inclusion of subjects needing legally acceptable representative/impartial witness will be in compliance to the enrolling country’s regulatory requirement) 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 Ph+CML CP, AP or BP who are resistant and/or intolerant to = 3 prior TKIs one of which includes ponatinib. (Subjects with Ph+ ALL are not included)
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 sens

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 as per the Investigator’s discretion
6.Positive 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 any other investigational agent within 30 days or a washout of at least 5 half-lives, whichever is longer, of IMP administration
10.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
11.Known or suspected history of significant drug abuse as judged by the Investigator
12.Known or suspected history of alcohol abuse or excessive intake of alcohol in the 12 months prior to study entry
14.Radiotherapy or cytotoxic chemotherapy within 21 days or Vincristine within 7 days (for Ph+ ALL only); interferon or Cytarabine or immunotherapy within 14 days prior to the first IMP administration visit
15.Malabsorption syndrome or other illness that could affect oral absorption of the IMP
16.Clinically significant, uncontrolled, or active cardiovascular disease
17.Uncontrolled intercurrent illness
18.Subjects eligible and willing to undergo transplant
20.Autologous or allogeneic stem cell transplant = 3 months prior to Screening
Other criteria may apply (refer to protocol)

Part C:
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
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 medication.
6.Positive 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 or a washout of at least 5 half-lives, whichever is longer of IMP administration
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 alcohol abuse or excessive intake of alcohol in the 12 months prior to study entry
12.Known or suspected history of significant drug abuse as judged by the Investigator
14.Radiotherapy or cytotoxic chemotherapy within 21 days or Vincristine within 7 days (for Ph+ ALL only); interferon or Cytarabine or immunotherapy within 14 days prior to the first IMP administration visit
15.Active central nervous system (CNS) disease as evidenced by cytology or

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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