A Phase I Dose Escalation Study of GSK2879552 in Subjects With Acute Myeloid Leukemia (AML)

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 years and older
• All sexes
• No healthy volunteers
• Adult, Older adult

Trial locations and contacts

8 sites in 3 countries.

About this study

Official title: A Phase I Open-label, Dose Escalation Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK2879552 Given Orally in Subjects With Relapsed/Refractory Acute Myeloid Leukemia

Conditions

Leukaemia, Myelocytic, Acute

Being tested

GSK2879552, ATRA

Keywords

Oncology, LSD1, GSK2879552, Acute myeloid leukemia

Medical subject headings

Leukemia, Neoplasms, Leukemia, Myeloid, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• GSK2879552Drug

  GSK2879552 capsules contain 0.25 mg, 0.5 mg, 2 mg or 5 mg of GSK2879552 as parent. The initial dosing regimen will be continuous oral daily dosing.

• ATRADrug

  ATRA (Tretinoin) will be supplied as a 10 mg capsule for oral administration. The initial dosing regimen will be continuous oral twice daily dosing

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Part 1: Number of Participants With Adverse Events (AE) and Serious Adverse Events (SAE)

   An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect, other situations and is associated with liver injury or impaired liver function.

   Measured: Median of 4 weeks of drug exposure

2. Part 1: Number of Participants With Dose Limiting Toxicities (DLT)

   An event was considered a DLT if it occursed within the first 28 days of treatment, and meets one of the following criteria unless it can be clearly established that the event was unrelated to treatment: hematologic DLT included myelosuppression, Grade >=3 non-hematologic toxicity that is considered clinically significant and lasts >72 hours, Grade 2 toxicity that in the judgment of the investigator and GSK Medical Monitor is dose-limiting and treatment delay of >=42 days due to unresolved toxicity.

   Measured: Median of 4 weeks of drug exposure

3. Part 1: Number of Participants With AE Leading to Dose Reductions or Delays

   The number of participants who had any dose reduction or delay have been presented.

   Measured: Median of 4 weeks of drug exposure

4. Part 1: Number of Participants With Withdrawals Due to Toxicities

   Participants were monitored from start of the study till the development of toxicity. The data for number of participants withdrawn due to toxicities has been presented.

   Measured: Median of 4 weeks of drug exposure

5. Number of Participants With Clinical Chemistry Parameters Changes From Baseline With Respect to the Normal Range

   Blood samples were collected to assess clinical chemistry parameters like urea/blood urea nitrogen (BUN), calcium, potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose, total carbon dioxide (CO2), gamma glutamyl transferase (GGT), albumin, sodium, alkaline phosphatase, total protein, phosphate, lactate dehydrogenase (LDH). Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst case post Baseline is reported.

   Measured: Median of 4 weeks of drug exposure

6. Number of Participants With Clinical Chemistry Toxicity Grade Changes From Baseline

   Blood samples were collected for analysis of clinical chemistry parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any increase in grade of worst-case on-therapy has been provided.

   Measured: Median of 4 weeks of drug exposure

7. Number of Participants With Hematology Parameters Change From Baseline With Respect to the Normal Range

   Blood samples were collected to assess hematology parameters like mean corpuscle hemoglobin concentration (MCHC), mean corpuscle hemoglobin (MCH), mean corpuscle volume (MCV) mean platelet volume (MPV), basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, platelet count, Red blood cell (RBC) count, reticulocytes, White Blood Cell (WBC) count. Laboratory values were as per local labs per site with own normal ranges. Values above range were reported as high and values below range as low. Data for worst post Baseline were reported. NA indicates that data were not available as standard deviation could not be calculated for a single participant.

   Measured: Median of 4 weeks of drug exposure

8. Number of Participants With Hematology Toxicity Grade Changes From Baseline

   Blood samples were collected for analysis of hematology parameters based on common terminology criteria for adverse events (CTCAE) version 4.0, where Grade 1 is mild; Grade 2 is moderate; Grade 3 is severe or medically significant; Grade 4 is life threatening consequences. Data for any grade increase worst-case on-therapy has been provided.

   Measured: Median of 4 weeks of drug exposure

9. Part 1: Number of Participants With Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

   SBP and DBP were measured after resting for 5 minutes in semi-supine position. Vital signs were graded according to Common Toxicity Criteria for Adverse Events (CTCAE) version 4. An increase is defined as an increase in CTCAE grade relative to Baseline grade. For SBP Grade 0 (<120 millimeters of mercury [mmHg]), Grade 1 (120-139 mmHg), Grade 2 (140-159 mmHg), Grade 3 (>=160 mmHg). For DBP Grade 0 (<80 mmHg), Grade 1 (80-89 mmHg), Grade 2 (90-99 mmHg), Grade 3 (>=100 mmHg). Data for worst-case post Baseline is reported.

   Measured: Median of 4 weeks of drug exposure

10. Part 1: Number of Participants With Change From Baseline in Heart Rate

    Heart rate was measured after restings for 5 minutes in semi-supine position. Data for participants with heart rate decreased to < 60 beats per minute (bpm), normal or no change, increase to > 100 bpm. Data for worst post Baseline were reported.

    Measured: Median of 4 weeks of drug exposure

11. Part 1: Number of Participants With Change From Baseline in Temperature

    Temperature was measured after resting for 5 minutes in semi-supine position. Data for participants with temperature decreased to <=35 Celsius, normal or no change, increase to >=38 Celsius at worst-case post Baseline is reported.

    Measured: Median of 4 weeks of drug exposure

12. Part 1: Number of Participants With Change From Baseline in Respiratory Rate

    Respiration rate was measured after resting for 5 minutes in semi-supine position. Data for worst case post-Baseline has been reported. Number of participants with respiratory rate decrease to <12 and increase to >25 has been reported.

    Measured: Median of 4 weeks of drug exposure

13. Part 1: Number of Participants With Abnormal Electrocardiograms (ECGs) Findings

    A single 12-lead ECG was performed in semi-recumbent or supine position after 5 minutes of rest for the participant. An ECG machine that automatically calculated the heart rate and measured PR, QRS, QT, and corrected QT intervals was used. Number of participants with any visit post-Baseline abnormal clinically significant findings and abnormal not clinically significant findings in ECG results has been reported.

    Measured: Median of 4 weeks of drug exposure

14. Part 1: Number of Participants With Abnormal Physical Examinations

    Data for participants with abnormal physical examinations parameters was planned to be recorded.

    Measured: Median of 4 weeks of drug exposure

15. Part 2: Objective Response Rate of Participants

    Objective response rate defined as the percentage of participants who achievied complete remission (CR), partial remission (PR), CRp (as per CR but platelet count <100 x 10^9/L) and morphologic leukemia free state per response criteria. This analysis was planned but not performed for Part 2 as the study was terminated early during Part 1.

    Measured: Up to 14 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted30 Jun 2014 (estimated)
2. Study start27 Aug 2014
3. Primary completion8 Dec 2017
4. Study completion8 Dec 2017

Why it stopped: The risk benefit in relapsed refractory AML does not favor continuation of the study.

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Other trials for Leukaemia, Myelocytic, AcuteStudies of the same condition, open and under way.
• More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.