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

NCT03197714 | Completed Phase 1 FDA Drug

• 2 other identifiers: FDO-LMA-2016-012016-004135-21
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 6

Brief 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.

Conditions

Acute Myeloid Leukemia

Keywords

Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT) of OPB-111077 in patients with in acute myeloid Leukemia.

  Any adverse event related to the study drug that occurred during the first cycle and considered relevant: * Any Grade 3 or 4 non-hematologic toxicity * Any unexpected non-tolerable grade II adverse event possibly related to the treatment regimen that requires delay beyond 1 week until recovery * Hematological toxicity is not considered doses limiting due to the characteristic of Acute Myeloid Leukemia.

  28 days

Secondary Outcomes (6)

• Overall response rate.

  Up to 8 months

• Overall response rate according to IC50

  Up to 8 months

• Overall response rate according to Area under de Curve

  Up to 8 months

• Incidence of Treatment-Emergent Adverse Events

  Up to 8 months

• Progression Free Survival

  Up to 8 months

Study Arms (1)

OPB-111077

EXPERIMENTAL

Level 1: 200 mg daily Level 2: 250 mg daily

Drug: OPB-111077

Interventions

OPB-111077 DRUG

Two dose schemas will be employed: * Level 1: 200 mg daily * Level 2: 250 mg daily

OPB-111077

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hospital Universitario 12 de Octubre: lead
• Otsuka Pharmaceutical Co., Ltd.: collaborator
• Apices Soluciones S.L.: collaborator
• Vivia Biotech: collaborator

Study Sites (6)

Hospital San Pedro Alcántara

Cáceres, Extremadura, 10003, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital 12 Octubre

Madrid, 28041, Spain

Location

Hospital Universitario Madrid Sanchinarro

Madrid, 28050, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Joaquín Martínez López, MD

  Hospital 12 Octubre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Hematology Department

Model Details: Phase Ib, open-label, dose-escalation clinical trial to evaluate the best-tolerated doses in AML relapsed or refractory to chemotherapy

Study Record Dates

• First Submitted: June 13, 2017
• First Posted: June 23, 2017
• Study Start: September 7, 2017
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: February 15, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

ES (6)