Trial Outcomes & Findings for Eltrombopag With or Without Hypomethylating Agent After Hypomethylating Agent Failure For Patients With Myelodysplastic Syndrome (MDS) (NCT NCT01893372)

Last Updated: 2020-02-18

Results Overview

Overall response rate (ORR) based on the International Working Group (IWG)-2006 criteria, which include complete remission (CR), partial remission (PR), and major hematologic improvement (HI). Patients' overall response assessed after at least 2 cycles of treatment and no more than after 6 cycles of treatment and each cycle is 28 days. CR is Bone marrow of \</= 5% myeloblasts with normal maturation of cell lines, persistent dysplasia and a hemoglobin \>/= 11g/dl, platelets \>/= 100x10\^9/L, neutrophils \>/= 1.0x10\^9/L and 0% blasts. PR is the same as CR but bone marrow blasts decreased by \>/=50% but still 5% over pre-treatment. HI is described by the number of individually affected cell lines. (E = Erythroid, N = Neutrophils, P = Platelet). HI-E is a 2 gram increase in hemoglobin. HI-N is at least a 100% increase or an absolute increase of more than 500/mm\^3. HI-P is an absolute increase of 30/mm\^3 or a 50% increase

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

29 participants

Primary outcome timeframe

After second 28 day cycle

Results posted on

2020-02-18

Participant Flow

Recruitment Details: October 2013 to January 2016

Participant milestones

Participant milestones
Measure	Eltrombopag Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
Overall Study STARTED	7	22
Overall Study COMPLETED	7	22
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Eltrombopag With or Without Hypomethylating Agent After Hypomethylating Agent Failure For Patients With Myelodysplastic Syndrome (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Eltrombopag n=7 Participants Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) n=22 Participants Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.	Total n=29 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	18 Participants n=7 Participants	23 Participants n=5 Participants
Age, Continuous	74 years n=5 Participants	72 years n=7 Participants	72 years n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	9 Participants n=7 Participants	12 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	13 Participants n=7 Participants	17 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	18 Participants n=7 Participants	24 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	7 participants n=5 Participants	22 participants n=7 Participants	229 participants n=5 Participants

PRIMARY outcome

Timeframe: After second 28 day cycle

Outcome measures

Outcome measures
Measure	Eltrombopag n=7 Participants Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) n=22 Participants Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
Overall Response Rate (ORR)	0 Participants	3 Participants

PRIMARY outcome

Timeframe: Through study completion. Up to 3 years, 3 months.

Overall Survival (OS) was measured from the time of study enrollment until death from any cause or fate of the last follow-up.

Outcome measures

Outcome measures
Measure	Eltrombopag n=7 Participants Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) n=22 Participants Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
Overall Survival (OS)	57.9 Weeks Interval 4.8 to 165.1	40.4 Weeks Interval 2.3 to 150.4

SECONDARY outcome

Timeframe: Up to 3 years, 3 months.

Outcome measures

Outcome measures
Measure	Eltrombopag n=7 Participants Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) n=22 Participants Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
Number of Participants Transforming From Myelodysplastic Syndrome (MDS) to Acute Myeloid Leukemia (AML)	1 Participants	7 Participants

SECONDARY outcome

Timeframe: 3 Years

Platelet response is Hematologic Improvement with platelet response (HI-P), defined as an absolute increase of \>/= 30 x 10\^9/L for patients starting with \>20 x 10\^9/L platelets or increase from \<20 x 10\^9/L to \>20 x 10\^9/L and by at least 100%

Outcome measures

Outcome measures
Measure	Eltrombopag n=7 Participants Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) n=22 Participants Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
Number of Participants Achieving a Platelet Response	0 Participants	3 Participants

Adverse Events

Eltrombopag

Serious events: 3 serious events

Other events: 1 other events

Deaths: 1 deaths

Eltrombopag + Hypomethylating Agent (HMA)

Serious events: 16 serious events

Other events: 16 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Courtney DiNardo, MD/Associate Professor

The Universtiy of Texas MD Anderson Cancer Center

Phone: 713-794-1141

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Eltrombopag n=7 participants at risk Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) n=22 participants at risk Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
General disorders Abdominal Pain	14.3% 1/7 • Number of events 1 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Blood and lymphatic system disorders Aenmia	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
Cardiac disorders Atrial Fibrillaiton	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Metabolism and nutrition disorders Hyperbilirubinemia	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
General disorders Death	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Infection	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	14.3% 1/7 • Number of events 1 • Through study completion. Up to 3 years, 3 months.	0.00% 0/22 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Febrile Neutropenia	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	18.2% 4/22 • Number of events 5 • Through study completion. Up to 3 years, 3 months.
Gastrointestinal disorders Hemorrhoids	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Lung Infection	28.6% 2/7 • Number of events 2 • Through study completion. Up to 3 years, 3 months.	18.2% 4/22 • Number of events 5 • Through study completion. Up to 3 years, 3 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benigh, malignantand unspecified	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
General disorders Pain	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Gastrointestinal disorders Rectal Hemorrhage	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Sepsis	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Upper Respiratory Infection	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Urinary Tract Infection	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Device Related Infection	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.

Measure	Eltrombopag n=7 participants at risk Eltrombopag 200 mg by mouth daily in a 28 day cycle. Eltrombopag: 200 mg by mouth daily in a 28 day cycle.	Eltrombopag + Hypomethylating Agent (HMA) n=22 participants at risk Eltrombopag in combination with continuation of hypomethylating agent in 28-day cycles. Eltrombopag 200 mg by mouth daily in a 28 day cycle. The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study. Eltrombopag should be initiated at the start of the next HMA cycle whenever possible so the start date of both agents is consistent. Eltrombopag: 200 mg by mouth daily in a 28 day cycle. Hypomethylating Agent (HMA): The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.
General disorders Fatigue	14.3% 1/7 • Number of events 1 • Through study completion. Up to 3 years, 3 months.	59.1% 13/22 • Number of events 13 • Through study completion. Up to 3 years, 3 months.
Skin and subcutaneous tissue disorders Abcess Under Arm	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
General disorders Back Pain	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Bladder Infection	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Eye disorders Blurred Vision	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	13.6% 3/22 • Number of events 3 • Through study completion. Up to 3 years, 3 months.
Gastrointestinal disorders Diarrhea	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
Nervous system disorders Dizziness	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	31.8% 7/22 • Number of events 7 • Through study completion. Up to 3 years, 3 months.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
General disorders Fever	14.3% 1/7 • Number of events 1 • Through study completion. Up to 3 years, 3 months.	13.6% 3/22 • Number of events 5 • Through study completion. Up to 3 years, 3 months.
General disorders Flu Like Symptoms	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
General disorders Headache	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Investigations Hyperbilirubinemia	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Infection	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Gastrointestinal disorders Intermittent Constipation	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
General disorders Intermittent Fatigue	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Investigations Jaundice	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
Musculoskeletal and connective tissue disorders Joint Pain	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	13.6% 3/22 • Number of events 3 • Through study completion. Up to 3 years, 3 months.
Gastrointestinal disorders Nausea	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	31.8% 7/22 • Number of events 7 • Through study completion. Up to 3 years, 3 months.
Nervous system disorders Paresthesia	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Skin and subcutaneous tissue disorders Rash	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Respiratory, thoracic and mediastinal disorders Sore Throat	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	4.5% 1/22 • Number of events 1 • Through study completion. Up to 3 years, 3 months.
Infections and infestations Urinary Tract Infection	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	9.1% 2/22 • Number of events 2 • Through study completion. Up to 3 years, 3 months.
Gastrointestinal disorders Vomiting	0.00% 0/7 • Through study completion. Up to 3 years, 3 months.	13.6% 3/22 • Number of events 3 • Through study completion. Up to 3 years, 3 months.