Phase 2 N=17 Randomized Quadruple-blind Supportive Care

A Three-part Study of Eltrombopag in Thrombocytopenic Subjects With Myelodysplastic Syndromes or Acute Myeloid Leukemia

Thrombocytopaenia

Bottom Line

View on ClinicalTrials.gov: NCT01440374 ↗

Enrolled (actual)

Serious AEs

61.8%

Results posted

Jun 2016

Primary outcome: Primary: Number of Participants With Platelet Response up to Week 8 During Part 1 — 4 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: eltrombopag (Drug); placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Novartis Pharmaceuticals
Primary completion: Mar 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants With Platelet Response up to Week 8 During Part 1	4	—
PRIMARY Clinically Relevant Thrombocytopenic Events (CRTE) From Week 5 up to Week 12 During Part 2	69; 54	0.0315 sig
SECONDARY Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 1 Subjects)	0; 7.7; 7.2; 14.3; 20.8; 20.2	—
SECONDARY Plasma Eltrombopag Pharmacokinetic Concentration-Time Data - by Visit (Part 2 Subjects)	0; 10.1; 24.0; 20.2; 29.0; 42.9	—
SECONDARY Mean Number of Platelet Transfusions	18.8; 15.7	—
SECONDARY Hematologic Improvement	10; 4; 8; 2; 4; 4	—
SECONDARY Change in Mean Platelet Count	3.36; 1.66; 10.41; 3.06; 6.23; 2.13	—
SECONDARY Maximum Duration of Platelet Transfusion Independence	26.3; 25.4	—
SECONDARY Number of Participants With Maximum Bleeding Grade According to World Health Organization on Bleeding Scale	15; 4; 31; 22; 41; 14	—
SECONDARY Independent Reviewer-Assessed Best Response	1; 1; 0; 0; 0; 1	—
SECONDARY Independent Reviewer Assessed Disease Progression	61; 36; 12; 6; 23; 5	—
SECONDARY Median Overall Survival	4.27; 4.6	—
SECONDARY Summary of Health Outcomes	1; 0; 2; 1; 5; 4	—
SECONDARY Functional Assessment of Cancer Therapy (FACT)	-0.79; -3.15; -4.83; -2.76; -3.38; -4.17	—
SECONDARY EQ-5D Utility Score Analysis	-0.01; -0.15; -0.08; -0.06; -0.09; -0.11	—

Summary

This was a worldwide, three-part (Part 1: open-label, Part 2: randomized, double-blind, Part 3: extension), multi-center study to evaluate the effect of eltrombopag in subjects with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) who have thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy. This objective was assessed by a composite primary endpoint that consists of the following: the proportion of ≥Grade 3 hemorrhagic adverse events, or platelet counts <10 Gi/L, or platelet transfusions. Patients with MDS or AML and Grade 4 thrombocytopenia due to bone marrow insufficiency from their underlying disease or prior chemotherapy were enrolled in the study. No low or intermediate-1 risk MDS subjects were enrolled in the study. Subjects must have had at least one of the following during the 4 weeks prior to enrolment: platelet count <10 Gi/L, platelet transfusion, or symptomatic hemorrhagic event. Supportive standard of care (SOC), including hydroxyurea, was allowed as indicated by local practice throughout the study. The study had 3 sequential parts. Subjects who were enrolled in Part 1 (open-label) cannot be enrolled in Part 2 of the study (randomized, double-blind); however, subjects who completed the treatment period for Part 1 or Part 2 (8 and 12 weeks, respectively) continued in Part 3 (extension) if the investigator determined that the subject was receiving clinical benefit on treatment.

Eligibility Criteria

Inclusion Criteria

Adult subjects (18 years of age or older) with MDS or AML (bone marrow blasts ≤50%) with thrombocytopenia due to bone marrow insufficiency from the disease or prior treatment. Subjects with transient thrombocytopenia due to active treatment with disease modifying agents or chemotherapy (except for hydroxyurea) are excluded.
Subjects must have Grade 4 thrombocytopenia (platelet counts 480 msec (QTc >510 msec for subjects with Bundle Branch Block).
Leukocytosis ≥25, 000/uL on Day 1 of treatment with study medication.
Subjects with known thrombophilic risk factors. Exception: Subjects for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator.
Female subjects who are nursing or pregnant (positive serum or urine β-human chorionic gonadotropin [β-hCG] pregnancy test) at screening or pre-dose on Day 1.
Current alcohol or drug abuse.
Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
Active and uncontrolled infections (e.g. sepsis, hepatitis B, hepatitis C).
Subjects infected with Human Immunodeficiency Virus (HIV).
Subjects with liver cirrhosis (as determined by the investigator).
Subjects receiving or planned to receive any prohibited medication.
Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient (microcrystalline cellulose, mannitol, polyvinylpyrrolidone, sodium starch glycolate, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol 400 and polysorbate 80) that contraindicates the subjects' participation.
In France, subjects who have participated in any study using an investigational drug during the previous 30 days.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01440374). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.