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: 21.1Level: LLTClassification code 10009015Term: Chronic myeloid leukemiaSystem Organ Class: 100000004864; MedDRA version: 21.0Level: LLTClassification code 10000845Term: Acute lymphoblastic 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-GB
• Lead Sponsor: Sun Pharma Advanced Research Company (SPARC) Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-27
• Last Update Posted: 15 June 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 255

Inclusion Criteria

Subjects may be included if:
Part B
1. Willing and able to give written, and dated, informed consent (or 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 (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 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.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 protocol 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 serum pregnancy test (as confirmed by negative urine pregnancy test with a sensitivity of less the 50mIU/mL or equivalent units of human chorionic gonadotropin)
10. Female subjects must be non-lactating and non-breastfeeding

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 ne

Exclusion Criteria

Subjects will be excluded from the study if:
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
13.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
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 transplant
18.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
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 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 or a washout of at least 5 half-lives, whichever is longer of IMP administration
9.Use of concomitant medication that might influence the results of the
study prior to IMP administration/or anticipated need any time during
the study
10.Known or suspected history of alcohol abuse or excessive intake of alcohol in the 12 months prior to study entry
11.Known or suspected history of significant drug abuse as judged by the Investigator
12.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
13.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