First in human clinical trial of the study drug KO-539 in patients with leukemia
- Conditions
- Relapsed and/or refractory Acute Myeloid LeukemiaMedDRA version: 21.0Level: LLTClassification code 10060558Term: Acute myeloid leukemia recurrentSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-001545-41-IT
- Lead Sponsor
- KURA ONCOLOGY INC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 90
For all parts:
1. Refractory or relapsed AML defined as the reappearance of >=5% blasts in the bone marrow and who have also failed or are not eligible for any approved standard of care therapies, including hematopoietic stem cell transplantation (HSCT).
2. >=18 years of age.
3. Read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures including serial bone marrow and peripheral blood sampling.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Adequate organ function including:
• creatinine <=2.0 × upper limit of normal (ULN) OR creatinine clearance >=40 mL/min using the Cockcroft-Gault equation;
• serum bilirubin <=1.5 × ULN (unless known Gilbert’s syndrome or secondary to leukemic disease); aspartate aminotransferase and alanine aminotransferase <=2.0 × ULN.
6. Peripheral white blood cell (WBC) counts <=30,000/µL. Patients are allowed to receive hydroxyurea to control and maintain WBC count prior to enrollment and can continue on hydroxyurea through Cycle 1 Day 28 or until first disease assessment. After which, approval by Kura Medical Monitor is required.
7. Women of childbearing potential (WOCBP) must be willing to use a highly effective method of contraception throughout the study and study follow-up or for at least 90 days after the last dose of study treatment. NOTE: A woman is considered to be of non-childbearing potential if she meets one of the following criteria: a) post-menopausal with at least 12 months of spontaneous amenorrhea; b) has had a bilateral oophorectomy; or c) has had a hysterectomy.
8. Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and study follow-up or for at least 90 days after the last dose of study treatment. All men with female partners of childbearing potential will be instructed to contact the Investigator immediately if their partner becomes pregnant at any time during study participation. All men must agree not to donate semen throughout the study and for 90 days after the last dose of study treatment.
In Part 1b Dose-Validation/ Cohort Expansion, patients must meet ALL of the above inclusion criteria as well as:
1. Adult patients that have documented specific genetic subtypes determined by local institutional genomic testing and defined as either lysine[K]-specific methyltransferase 2-rearranged (KMT2A-r) or nucleophosmin 1-mutant (NPM1-m).
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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50
For Part 1a – Dose-Escalation and Part 1b – Dose-Validation/ Cohort Expansion:
1. Patient has a diagnosis of acute promyelocytic leukemia.
2. Patient has a diagnosis of chronic myelogenous leukemia in blast crisis.
3. Donor lymphocyte infusion < 30 days prior to study entry.
4. Clinically active central nervous system (CNS) leukemia. A patient is considered eligible if CNS leukemia is controlled and patient is receiving intrathecal therapy at study entry. Patients should continue to receive intrathecal therapy (or cranial radiation) as clinically indicated.
5. Patients who have undergone HSCT and have not had adequate hematologic recovery (i.e. absolute neutrophil count [ANC] >1000 and platelet count > 100,000).
6. Patients on immunosuppressive therapy post HSCT at the time of screening (must be off all immunosuppression therapy for at least 2 weeks). The use of topical steroids for cutaneous graft-versus-host disease (GVHD) is allowed and stable steroid doses less than or equal to 20 mg of prednisone daily is permitted with Kura Medical Monitor approval.
7. Grade > 2 active GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
8. Patient has received chemotherapy, immunotherapy, radiotherapy or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) <=14 days prior to the first dose of KO-539.
9. Patients who have not recovered to NCI CTCAE <= v5.0 Grade 2 from all acute toxicities or deemed back to a stable baseline.
10. Patient requires treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450 (CYP)3A4 with the exception of antibiotics, antifungals, and antivirals that are used as standard of care to prevent or treat infections. Other such drugs that are considered absolutely essential for the care of the patient should be discussed on a case by case basis with the Kura Medical Monitor.
11. Patient has a known detectable viral load for human immunodeficiency virus or hepatitis C, or evidence of a hepatitis B surface antigen, all being indicative of active infection.
12. Patient has a pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML).
13. Patient has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
14. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (New York Heart Association [NYHA] Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.
15. Mean corrected QT interval by Fredericia’s formula (QTcF) >480 ms on triplicate electrocardiograms (ECGs) performed within 5 minutes of each other. Please refer to the following Credible Meds web page for a list of drugs that prolong QT and/or increase risk of torsades de pointes.
16. Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
17. Underlying medi
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