Trial Outcomes & Findings for A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients (NCT NCT00922883)

NCT ID: NCT00922883

Last Updated: 2020-10-20

Results Overview

Defined as unilineage or multilineage recovery by 1 or more of the following: 1) platelet response (increase to 20 × 103/μL above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks in those who were transfusion dependent on entry into the protocol); (2) erythroid response (when pretreatment hemoglobin was \<9 g/dL, defined as an increase in hemoglobin by 1.5 g/dL or, in transfused patients, a reduction in the units of packed red blood cell transfusions by an absolute number of at least 4 transfusions for 8 consecutive weeks, compared with the pretreatment transfusion number in the previous 8 weeks); and (3) neutrophil response (when pretreatment absolute neutrophil count \[ANC\] of \<0.5 × 103/μL as at least a 100% increase in ANC, or an ANC increase \>0.5 × 103/μL, and the toxicity profile as measured using Common Terminology Criteria for Adverse Events).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

12-16 weeks

Results posted on

2020-10-20

Participant Flow

44 patients were consented, but 1 patient was removed before treatment with the investigational agent was initiated because an additional review of baseline bone marrow revealed that the patient was not eligible, because the patient had changes in the bone marrow inconsistent with a diagnosis of aplastic anemia.

Participant milestones

Participant milestones
Measure
Eltrombopag
Eltrombopag (Promacta): Subjects commenced eltrombopag at a dose of 50 mg, which was increased by 25 mg every 2 weeks if the platelet count had not increased by 20 × 103/µL, to a maximum dose of 150 mg.
Overall Study
STARTED
43
Overall Study
COMPLETED
43
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Eltrombopag
n=44 Participants
Eltrombopag (Promacta): Subjects commenced eltrombopag at a dose of 50 mg, which was increased by 25 mg every 2 weeks if the platelet count had not increased by 20 × 103/µL, to a maximum dose of 150 mg.
Age, Categorical
<=18 years
4 Participants
n=5 Participants
Age, Categorical
Between 18 and 65 years
27 Participants
n=5 Participants
Age, Categorical
>=65 years
13 Participants
n=5 Participants
Sex: Female, Male
Female
19 Participants
n=5 Participants
Sex: Female, Male
Male
25 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
11 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
33 Participants
n=5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
Race (NIH/OMB)
Asian
1 Participants
n=5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=5 Participants
Race (NIH/OMB)
Black or African American
11 Participants
n=5 Participants
Race (NIH/OMB)
White
21 Participants
n=5 Participants
Race (NIH/OMB)
More than one race
3 Participants
n=5 Participants
Race (NIH/OMB)
Unknown or Not Reported
8 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 12-16 weeks

Population: All subjects who received Eltrombopag were analyzed.

Defined as unilineage or multilineage recovery by 1 or more of the following: 1) platelet response (increase to 20 × 103/μL above baseline or stable platelet counts with transfusion independence for a minimum of 8 weeks in those who were transfusion dependent on entry into the protocol); (2) erythroid response (when pretreatment hemoglobin was \<9 g/dL, defined as an increase in hemoglobin by 1.5 g/dL or, in transfused patients, a reduction in the units of packed red blood cell transfusions by an absolute number of at least 4 transfusions for 8 consecutive weeks, compared with the pretreatment transfusion number in the previous 8 weeks); and (3) neutrophil response (when pretreatment absolute neutrophil count \[ANC\] of \<0.5 × 103/μL as at least a 100% increase in ANC, or an ANC increase \>0.5 × 103/μL, and the toxicity profile as measured using Common Terminology Criteria for Adverse Events).

Outcome measures

Outcome measures
Measure
Eltrombopag
n=43 Participants
Eltrombopag (Promacta): Subjects commenced eltrombopag at a dose of 50 mg, which was increased by 25 mg every 2 weeks if the platelet count had not increased by 20 × 103/µL, to a maximum dose of 150 mg.
The Portion of Drug Responders as Defined by Hematologic Improvements
17 Participants

Adverse Events

Eltrombopag

Serious events: 16 serious events
Other events: 38 other events
Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure
Eltrombopag
n=43 participants at risk
Eltrombopag (Promacta): Subjects commenced eltrombopag at a dose of 50 mg, which was increased by 25 mg every 2 weeks if the platelet count had not increased by 20 × 103/µL, to a maximum dose of 150 mg.
Blood and lymphatic system disorders
Anaemia
2.3%
1/43
Blood and lymphatic system disorders
Febrile neutropenia
16.3%
7/43
Blood and lymphatic system disorders
Neutropenia
2.3%
1/43
Blood and lymphatic system disorders
Thrombocytopenia
2.3%
1/43
Eye disorders
Conjunctival haemorrhage
4.7%
2/43
Gastrointestinal disorders
Abdominal pain
2.3%
1/43
Gastrointestinal disorders
Clostridium difficile colitis
2.3%
1/43
Gastrointestinal disorders
Gingivitis ulcerative
2.3%
1/43
General disorders
Drug eruption
2.3%
1/43
General disorders
Pyrexia
2.3%
1/43
Hepatobiliary disorders
Hepatic neoplasm
2.3%
1/43
Infections and infestations
Bacteraemia
2.3%
1/43
Infections and infestations
Influenza
2.3%
1/43
Infections and infestations
Sepsis
7.0%
3/43
Infections and infestations
Urinary tract infection
2.3%
1/43
Investigations
Aspartate aminotransferase increased
2.3%
1/43
Vascular disorders
Deep vein thrombosis
2.3%
1/43
Vascular disorders
Hypotension
2.3%
1/43

Other adverse events

Other adverse events
Measure
Eltrombopag
n=43 participants at risk
Eltrombopag (Promacta): Subjects commenced eltrombopag at a dose of 50 mg, which was increased by 25 mg every 2 weeks if the platelet count had not increased by 20 × 103/µL, to a maximum dose of 150 mg.
Blood and lymphatic system disorders
Febrile neutropenia
7.0%
3/43
Blood and lymphatic system disorders
Hyperbilirubinaemia
2.3%
1/43
Blood and lymphatic system disorders
Jaundice
2.3%
1/43
Blood and lymphatic system disorders
Petechiae
7.0%
3/43
Blood and lymphatic system disorders
Purpura
2.3%
1/43
Cardiac disorders
Chest pain
4.7%
2/43
Cardiac disorders
Dizziness
9.3%
4/43
Cardiac disorders
Dyspnoea
2.3%
1/43
Cardiac disorders
Dyspnoea exertional
4.7%
2/43
Eye disorders
Cataract
2.3%
1/43
Eye disorders
Conjunctival haemorrhage
4.7%
2/43
Eye disorders
Dry eye
4.7%
2/43
Eye disorders
Eye contusion
2.3%
1/43
Eye disorders
Eye irritation
2.3%
1/43
Eye disorders
Myopia
2.3%
1/43
Eye disorders
Ocular hyperaemia
2.3%
1/43
Eye disorders
Vision blurred
2.3%
1/43
Eye disorders
Vitreous floaters
2.3%
1/43
Gastrointestinal disorders
Abdominal discomfort
4.7%
2/43
Gastrointestinal disorders
Abdominal injury
7.0%
3/43
Gastrointestinal disorders
Abdominal pain
9.3%
4/43
Gastrointestinal disorders
Anal fissure
2.3%
1/43
Gastrointestinal disorders
Anorectal discomfort
2.3%
1/43
Gastrointestinal disorders
Constipation
2.3%
1/43
Gastrointestinal disorders
Diarrhoea
9.3%
4/43
Gastrointestinal disorders
Dyspepsia
2.3%
1/43
Gastrointestinal disorders
Gastrointestinal disorder
2.3%
1/43
Gastrointestinal disorders
Gingival bleeding
4.7%
2/43
Gastrointestinal disorders
Gingival disorder
2.3%
1/43
Gastrointestinal disorders
Gingival swelling
2.3%
1/43
Gastrointestinal disorders
Lip ulceration
2.3%
1/43
Gastrointestinal disorders
Nausea
25.6%
11/43
Gastrointestinal disorders
Oral candidiasis
2.3%
1/43
Gastrointestinal disorders
Oropharyngeal pain
9.3%
4/43
Gastrointestinal disorders
Pelvic organ injury
2.3%
1/43
Gastrointestinal disorders
Pericoronitis
2.3%
1/43
Gastrointestinal disorders
Periodontal disease
2.3%
1/43
Gastrointestinal disorders
Tooth abscess
2.3%
1/43
Gastrointestinal disorders
Tooth injury
2.3%
1/43
Gastrointestinal disorders
Toothache
2.3%
1/43
Gastrointestinal disorders
Vomiting
7.0%
3/43
General disorders
Asthenia
2.3%
1/43
General disorders
Axillary pain
2.3%
1/43
General disorders
Catheter site pain
2.3%
1/43
General disorders
Fatigue
25.6%
11/43
General disorders
Induration
2.3%
1/43
General disorders
Injection site infection
2.3%
1/43
General disorders
Night sweats
2.3%
1/43
General disorders
Pain
4.7%
2/43
General disorders
Pyrexia
9.3%
4/43
Hepatobiliary disorders
Cholecystitis
2.3%
1/43
Hepatobiliary disorders
Hepatitis viral
2.3%
1/43
Immune system disorders
Hypersensitivity
2.3%
1/43
Immune system disorders
Rhinitis allergic
4.7%
2/43
Immune system disorders
Urticaria
4.7%
2/43
Infections and infestations
Cellulitis
2.3%
1/43
Infections and infestations
Herpes zoster
2.3%
1/43
Infections and infestations
Influenza
2.3%
1/43
Infections and infestations
Kidney infection
2.3%
1/43
Infections and infestations
Upper respiratory tract infection
18.6%
8/43
Infections and infestations
Viral infection
2.3%
1/43
Investigations
Alanine aminotransferase increased
7.0%
3/43
Investigations
Aspartate aminotransferase increased
4.7%
2/43
Investigations
Blood creatine phosphokinase increased
2.3%
1/43
Investigations
Neutrophil count decreased
2.3%
1/43
Investigations
Weight decreased
2.3%
1/43
Metabolism and nutrition disorders
Gout
2.3%
1/43
Metabolism and nutrition disorders
Osteoporosis
2.3%
1/43
Musculoskeletal and connective tissue disorders
Arthralgia
4.7%
2/43
Musculoskeletal and connective tissue disorders
Back pain
4.7%
2/43
Musculoskeletal and connective tissue disorders
Bone pain
2.3%
1/43
Musculoskeletal and connective tissue disorders
Muscle spasms
11.6%
5/43
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
2.3%
1/43
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
4.7%
2/43
Musculoskeletal and connective tissue disorders
Pain in extremity
4.7%
2/43
Musculoskeletal and connective tissue disorders
Piriformis syndrome
2.3%
1/43
Musculoskeletal and connective tissue disorders
Synovial cyst
2.3%
1/43
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cyst
2.3%
1/43
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
2.3%
1/43
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer
2.3%
1/43
Nervous system disorders
Headache
16.3%
7/43
Nervous system disorders
Insomnia
7.0%
3/43
Nervous system disorders
Peripheral sensory neuropathy
2.3%
1/43
Psychiatric disorders
Anxiety
2.3%
1/43
Psychiatric disorders
Depressed mood
2.3%
1/43
Psychiatric disorders
Depression
2.3%
1/43
Psychiatric disorders
Libido decreased
2.3%
1/43
Psychiatric disorders
Mood altered
2.3%
1/43
Psychiatric disorders
Nightmare
2.3%
1/43
Psychiatric disorders
Personality disorder
2.3%
1/43
Renal and urinary disorders
Chromaturia
2.3%
1/43
Renal and urinary disorders
Dysuria
2.3%
1/43
Renal and urinary disorders
Pollakiuria
2.3%
1/43
Respiratory, thoracic and mediastinal disorders
Cough
7.0%
3/43
Respiratory, thoracic and mediastinal disorders
Epistaxis
4.7%
2/43
Respiratory, thoracic and mediastinal disorders
Nasal disorder
2.3%
1/43
Respiratory, thoracic and mediastinal disorders
Pulmonary haemorrhage
2.3%
1/43
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
2.3%
1/43
Skin and subcutaneous tissue disorders
Ingrowing nail
2.3%
1/43
Skin and subcutaneous tissue disorders
Pruritus
4.7%
2/43
Skin and subcutaneous tissue disorders
Rash
7.0%
3/43
Skin and subcutaneous tissue disorders
Skin discolouration
2.3%
1/43
Skin and subcutaneous tissue disorders
Skin lesion
2.3%
1/43
Skin and subcutaneous tissue disorders
Skin ulcer
2.3%
1/43
Surgical and medical procedures
Platelet transfusion
2.3%
1/43
Surgical and medical procedures
Tooth extraction
2.3%
1/43
Vascular disorders
Haematoma
2.3%
1/43
Vascular disorders
Hypotension
2.3%
1/43

Additional Information

Cynthia E Dunbar

NHLBI

Phone: 301-496-5093

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place