Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia

• Status: Completed
• Trial end date: 2020-03-31
• Target enrollment: 0
• Participant gender: All

Summary

Phase Ib, open-label, dose-escalation clinical trial to evaluate the best-tolerated doses in Acute Myeloid Leukaemia (AML) relapsed or refractory to chemotherapy.

This open-label, nonrandomized trial will comprise 2 stages. A dose escalation stage will characterize the safety, tolerability and maximum tolerated dose (MTD), of OPB-111077.

Subsequently, an expansion stage will further evaluate the safety and antitumor activity of OPB-111077 in AML relapsed or refractory to chemotherapy.

Enrollment to the expansion cohort will begin following determination of the MTD.

Approximately 6-12 patients will be included in the phase I part of this clinical trial.

Additional patients will be included in the expansion cohort up to a total of 15 patients. The expansion cohort will serve to further evaluate safety simultaneously with preliminary efficacy.

Patients will be selected and included in the study after testing the response to the drug with the Vivia Biotech ex vivo CDx PharmaFlow PM test. PharmaFlow PM test is a companion diagnostic (CDx) tool that provides a complete pharmacological profile for each individual, allowing the detection of patients resistant to OPB-111077 and enriching the study in patients that respond to the drug. The third of patients more sensitive to OPB-11077 wil be included in the study.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hospital Universitario 12 de Octubre
• Collaborators: Apices Soluciones S.L.; Fundación para la Investigación Biomédica del Hospital 12 de Octubre; Otsuka Pharmaceutical Co., Ltd.; Vivia Biotech

Criteria

Inclusion Criteria:

• Patients at least 18 years old.

• Patients diagnosed of non M3 acute myeloid leukemia in relapse after intensive chemotherapy.

• Patients with a highest sensitivity (higher 70% of the samples analyzed) in the bone marrow analysis of the OPB-111077 ex-vivo sensitivity test.

• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

• Bilirubin ≤ 2 × Upper Limit of Normal (ULN). For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL.

• Serum creatinine ≤2 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min.

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN.

• Left Ventricular Ejection Fraction (LVEF) must be equal to or greater than 50%.

• New York Heart Association (NYHA) congestive heart failure (CHF) class II or better.

• Recovery from adverse effects of prior therapy at time of enrollment to ≤ Grade 1 (excluding alopecia).

• Life expectancy ≥3 months

• Patients, or appropriate designee, must be able to provide informed consent.

Exclusion Criteria:

• Individuals with a history of other malignancies.

• Subject has uncontrolled intercurrent illness that would limit compliance with study requirements.

• Patients diagnosed of M3/Acute promyelocytic leukemia (APL).

• The subject has received systemic antineoplastic therapy within 14 days of study treatment.

• The subject has received any investigational agent within 28 days before the first dose of study treatment.

• The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant Adverse Events (AEs).

• The subject has concurrent uncompensated hypothyroidism or thyroid dysfunction within 7 days before the first dose of study treatment.

• Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation.

• Malabsorption syndrome.

• Subject is unable to swallow capsules or tablets.

• Subject is pregnant or breastfeeding.

• Patients with history of allergic reactions attributed to components of OPB- 111077 that are not easily managed

• Subject has systemic infection requiring IV antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection.

• Uncontrolled intercurrent illness that would limit compliance with study requirements.

• Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study.