Trial Outcomes & Findings for Trial of Eltrombopag During Consolidation Therapy in Adults With AML in Complete Remission (NCT NCT01656252)

Last Updated: 2020-11-03

Results Overview

To determine the safety, tolerability and optimal dose of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy. The optimal dose was based on rules involving observation of Dose Limiting Toxicity (DLT events), defined as a CTCAE Version 4 non-hematologic adverse event of grade 3 or higher occurring within 30 days of the last dose of eltrombopag judged by the investigator to be at least possibly related to eltrombopag administration.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

15 participants

Primary outcome timeframe

13 months

Results posted on

2020-11-03

Participant Flow

Study closed after phase I. Phase II study was not conducted.

One patient did not start treatment because of an infection before starting protocol treatment.

Participant milestones

Participant milestones
Measure	Phase I- Cytarabine & Eltrombopag Cycle 1= Cytarabine twice daily on Days 1, 3 and 5 and Eltrombopag (Open-Label) until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. Phase I- Cytarabine \& Eltrombopag: Cycle 1= Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag (Open-Label) by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. One cycle of consolidation therapy with high-dose cytarabine and eltrombopag will be received on study. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
Phase I STARTED	14
Phase I COMPLETED	14
Phase I NOT COMPLETED	0
Phase II STARTED	0
Phase II COMPLETED	0
Phase II NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial of Eltrombopag During Consolidation Therapy in Adults With AML in Complete Remission

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I- Cytarabine & Eltrombopag n=14 Participants Cycle 1= Cytarabine twice daily on Days 1, 3 and 5 and Eltrombopag (Open-Label) until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. Phase I- Cytarabine \& Eltrombopag: Cycle 1= Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag (Open-Label) by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. One cycle of consolidation therapy with high-dose cytarabine and eltrombopag will be received on study. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
Age, Continuous	54 years n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 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	0 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	14 Participants n=5 Participants

PRIMARY outcome

Timeframe: 13 months

Outcome measures

Outcome measures
Measure	Phase I- Cytarabine & Eltrombopag n=14 Participants Cycle 1= Cytarabine twice daily on Days 1, 3 and 5 and Eltrombopag (Open-Label) until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. Phase I- Cytarabine \& Eltrombopag: Cycle 1= Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag (Open-Label) by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. One cycle of consolidation therapy with high-dose cytarabine and eltrombopag will be received on study. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.	Phase II- Sequence A Cytarabine twice daily on Days 1, 3 and 5. Eltrombopag(dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. Phase II- Sequence A: Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo by mouth daily with 2nd cycle. Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.	Phase II- Sequence B Cytarabine twice daily on Days 1, 3 and 5. Placebo with 1st cycle of high-dose consolidation therapy and Eltrombopag(dose and schedule as determined in Phase I) with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. Phase II- Sequence B: Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Placebo by mouth daily with 1st cycle of high-dose consolidation therapy and Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 2nd cycle. Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
Phase I- Optimal Tolerated Dose of Eltrombopag	300 mg	—	—

PRIMARY outcome

Timeframe: 13 months

To describe the kinetics of platelet count recovery in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy who will be receiving eltrombopag. This is assessed graphically by plotting platelet count vs. days relative to start of cytarabine for each patient.

Outcome measures

Outcome measures
Measure	Phase I- Cytarabine & Eltrombopag n=14 Participants Cycle 1= Cytarabine twice daily on Days 1, 3 and 5 and Eltrombopag (Open-Label) until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. Phase I- Cytarabine \& Eltrombopag: Cycle 1= Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag (Open-Label) by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. One cycle of consolidation therapy with high-dose cytarabine and eltrombopag will be received on study. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.	Phase II- Sequence A Cytarabine twice daily on Days 1, 3 and 5. Eltrombopag(dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. Phase II- Sequence A: Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 1st cycle of high-dose consolidation chemotherapy and placebo by mouth daily with 2nd cycle. Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.	Phase II- Sequence B Cytarabine twice daily on Days 1, 3 and 5. Placebo with 1st cycle of high-dose consolidation therapy and Eltrombopag(dose and schedule as determined in Phase I) with 2nd cycle. Treatment sequence will be blinded to the patient and all study/sponsor personnel. Phase II- Sequence B: Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Placebo by mouth daily with 1st cycle of high-dose consolidation therapy and Eltrombopag by mouth daily (dose and schedule as determined in Phase I) with 2nd cycle. Eltrombopag/placebo will continue until platelet recovery or for 35 consecutive days, whichever occurs first. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
Phase I - Dose Level With Best Kinetics of Platelet Count Recovery	150 mg	—	—

PRIMARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine if platelet recovery following consolidation chemotherapy is accelerated with eltrombopag.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Data was not collected.

To determine the plasma concentrations of eltrombopag in acute myeloid leukemia patients in complete remission receiving intensive consolidation chemotherapy (selected dosing regimen only).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine the impact of eltrombopag on platelet transfusion requirements in the setting of consolidation chemotherapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine the impact of eltrombopag on red blood cell transfusion requirements.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine the impact of eltrombopag on occurrence of bleeding events.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine the impact of eltrombopag on time to platelet recovery following consolidation chemotherapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine the impact of eltrombopag on the depth of platelet nadir following a cycle of consolidation chemotherapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine the duration of platelet nadir in the setting of eltrombopag exposure.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 62 months

Population: Study terminated during Phase I. No Phase II patients enrolled.

To determine the safety and tolerability of eltrombopag when given at the optimal dose in the setting of consolidation chemotherapy.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 62 months

To determine if eltrombopag has an effect on TPO and/or EPO in this setting.

Outcome measures

Outcome data not reported

Adverse Events

Phase I- Cytarabine & Eltrombopag

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Phase I- Cytarabine & Eltrombopag n=14 participants at risk Cycle 1= Cytarabine twice daily on Days 1, 3 and 5 and Eltrombopag (Open-Label) until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. Phase I- Cytarabine \& Eltrombopag: Cycle 1= Cytarabine 3 g/m² IV twice daily on Days 1, 3 and 5 (Patients \>60 years of age will receive cytarabine 1.5 g/m² IV per dose). Day 1 must start in AM. Eltrombopag (Open-Label) by mouth daily until platelet recovery or for 35 consecutive days, whichever occurs first. Phase I will determine the dose and schedule of Eltrombopag to be used in Phase II. One cycle of consolidation therapy with high-dose cytarabine and eltrombopag will be received on study. Additional chemotherapy may be administered at the investigators discretion without eltrombopag.
Blood and lymphatic system disorders Anemia	14.3% 2/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Investigations Platelet Count Decreased	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Investigations Neutrophil Count Decreased	14.3% 2/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Investigations Alanine Aminotransferase Increased	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Investigations Aspartate Aminotransferase Increased	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Investigations Blood Bilirubin Increased	14.3% 2/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Constipation	14.3% 2/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Investigations Diarrhea	14.3% 2/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Nervous system disorders Dizziness	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Dyspepsia	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
General disorders Fatigue	50.0% 7/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
General disorders Flu Like Symptoms	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	14.3% 2/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Nervous system disorders Headache	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Renal and urinary disorders Hematuria	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hyperglycemia	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypokalemia	14.3% 2/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Metabolism and nutrition disorders Hypomagnesemia	21.4% 3/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Reproductive system and breast disorders Menorrhagia	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Mucositis Oral	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Nausea	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
Gastrointestinal disorders Vomiting	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.
General disorders Non-Cardiac Chest Pain	7.1% 1/14 Participants were assessed by the clinician at every treatment cycle while on treatment and for 30 days after the end of treatment.

Additional Information

PrECOG Statistician

ECOG-ACRIN Biostatistics Center

Phone: 617-632-3633

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place