Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromePhase 2NCT02071901

Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

A Phase 2 study testing eltrombopag olamine in people with Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome and Adult Acute Basophilic Leukemia, run by Case Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 60 years and older
Conditions the study is for: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia
What is being tested?: eltrombopag olamine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 31 participants
Where: 1 siteUnited States
Study dates: 14 Aug 2014to 6 Jan 2019
Phase: Phase 2

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 60 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

All categories of AML will be included except for acute promyelocytic leukemia (APL), acute megakaryocytic leukemia, and acute leukemias of ambiguous lineage undergoing 7 + 3 remission IC with cytarabine and an anthracycline (daunorubicin or idarubicin). All cases have to be histopathologically confirmed by a diagnostic bone marrow biopsy. Use of granulocyte colony-stimulating factor (G-CSF) for any indication must have been discontinued at least 7 days prior to entry into the study.
Patients with secondary AML arising out of Myelodysplastic syndrome (MDS) (all subtypes under WHO [World Health Organization] classification), chronic myelomonocytic leukemia (CMML); therapy-related AML and those with a prior autologous hematopoietic cell transplantation are eligible.
No morphological evidence of disease on day 14 bone marrow examination following IC
Must be able to give voluntary informed written consent to participate in the study; informed consent will be obtained prior to initiation of remission IC and before any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care
Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment. All men and women of childbearing potential must use acceptable methods of birth control throughout the study as described below:
Females of childbearing potential: Recommendation is for 2 effective contraceptive methods during the study. Adequate forms of contraception are double-barrier methods (condoms with spermicidal jelly or foam and diaphragm with spermicidal jelly or foam), oral, depo provera, or injectable contraceptives, intrauterine devices, and tubal ligation.
Male patients with female partners who are of childbearing potential: Recommendation is for male and partner to use at least 2 effective contraceptive methods, as described above, during the study or to abstain.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

Who cannot join

Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent
Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 12 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer).
Secondary AML arising out of myeloproliferative neoplasms [as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias] and MDS/myeloproliferative disease (MPD) neoplasms other than CMML [as per the revised 2008 WHO classification of myeloid neoplasms and acute leukemias]. Refractory Anemia with Ringed Sideroblasts with thrombocytosis (RARS-T) classified as MDS/MPN neoplasm, unclassifiable will be excluded. AML patients with presenting features suspicious of underlying unrecognized MPD such as marked splenomegaly (> 20 cm) and thrombocytosis (>400,000 per microliter) will be excluded. Patients with relapsed or refractory AML will be excluded.
Radiation therapy, cytotoxic chemotherapy, and combined modality (both radiation and chemotherapy) used to treat other cancers or medical conditions and administered within 12 months prior to signing informed consent. Use of hydroxyurea or emergent leukapheresis (for cytoreduction of highly elevated white blood cell counts) is permissible. Those AML patients who initially receive treatment with all-trans retinoic acid (ATRA) for presumptive diagnosis of APL but if APL is ruled out in final pathology will be eligible for the study.
Prior history of treatment with recombinant thrombopoietin (TPO) or TPO-receptor (R) agonists
History of arterial or venous thrombosis [excluding line-thrombosis] within the last 1 year, or those with known inherited coagulopathies. Arterial or venous thrombosis includes pulmonary embolism, deep vein thrombosis of both upper [excluding line-thrombosis] and lower extremities, coronary artery disease managed medically or requiring intervention (percutaneous stent placement or coronary bypass surgery), cerebrovascular accident (for transient ischemic attacks clinical documentation is required), or involvement of other organs (such as hepatic, renal, spleen or other sites).

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Evidence of fibrosis on bone marrow examination at the time of diagnosis
Active participation in any other investigational treatment study
Uncontrolled intercurrent illness including, but not limited to uncontrolled infection, symptomatic congestive heart failure, cardiac arrhythmia, unstable angina or renal insufficiency (acute or chronic) on hemodialysis
Liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) can not be greater than or equal to 2.5 times the upper limits of normal (ULN)
Total bilirubin ≥ 1.5 x ULN within 14 days of enrollment.
Serum creatinine should be ≥ 2.5 x ULN within 14 days of enrollment
A known immediate or delayed hypersensitivity reaction or idiosyncrasy that, in the opinion of the Medical Monitor is due to drugs chemically related to eltrombopag or excipients (e.g. mannitol)
Known history of human immunodeficiency virus (HIV) or active hepatitis B or C
No major surgery within 2 weeks prior to trial enrollment
Female subject is pregnant or breast-feeding
Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065

Other trials in United States

About this study

Official title: A Single Arm, Phase II Study of Eltrombopag to Enhance Platelet Count Recovery in Elderly Patients With Acute Myeloid Leukemia Undergoing Remission Induction Therapy

This phase II trial studies how well eltrombopag olamine works in improving the recovery of platelet counts in older patients with Acute Myeloid Leukemia (AML) undergoing induction (the first treatment given for a disease) chemotherapy. Platelet counts recover more slowly in older patients, leading to risk of complications and the delay of post-remission therapy. Eltrombopag olamine may cause the body to make platelets after chemotherapy.

Read the detailed description

PRIMARY OBJECTIVES:

I.To determine whether eltrombopag leads to early platelet recovery in older AML patients (≥ 60years) who attain morphologic remission on day 14 (range, day 14-17) bone marrow assessment following remission induction chemotherapy (IC).

SECONDARY OBJECTIVES:

To determine the effect of eltrombopag on megakaryopoiesis - median time to reach platelet count ≥50,000 /μL and ≥100,000 /μL, number of days of platelet transfusion, rates of platelet transfusion-independence and the median time to reach platelet transfusion independence.

II. To determine the effect of eltrombopag on the rates of clinically significant bleeding events (CSBE).

III. To determine the effect of eltrombopag on erythropoiesis the median time to red blood cell transfusion independence.

IV. To determine the effect of eltrombopag on granulopoiesis- the time taken to reach an absolute neutrophil count of ≥ 500 /μL. V. To determine the safety and tolerability of eltrombopag in AML patients undergoing remission IC - incidence and severity of eltrombopag-related adverse events. VI. To determine rates of complete remission (CR), rates of partial complete remission (CRp), time to attain CR, and time to initiation of post-remission consolidation therapy.

OUTLINE:

Participants receive eltrombopag olamine orally (PO) once daily (QD) until platelet counts reach ≥50,000/uL or for 8 weeks, whichever comes earlier. Treatment continues in the absence of unacceptable toxicity.

After completion of study treatment, participants are followed up for 2 years.

Conditions: Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome, Adult Acute Basophilic Leukemia, Adult Acute Eosinophilic Leukemia, Adult Acute Megakaryoblastic Leukemia (M7), Adult Acute Minimally Differentiated Myeloid Leukemia (M0), Adult Acute Monoblastic Leukemia (M5a)
Being tested: eltrombopag olamine
Medical subject headings: Leukemia, Basophilic, Acute, Leukemia, Eosinophilic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

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

eltrombopag olamineDrug
Also called Promacta, SB 497115, SB-497115, SB497115
Given PO

Study groups in NCT02071901
Study group	Role	What they receive
Supportive care (eltrombopag olamine)	Experimental	Patients receive eltrombopag olamine by mouth (PO) daily (QD) until platelet counts reach >= 50,000/uL or for 8 weeks, whichever comes earlier. Treatment continues in the absence of unacceptable toxicity. Receives: Drug: eltrombopag olamine

What is being measured

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

Number of Participants With a Median Platelet Count >= 50,000/uL
Number of participants with a median platelet count >= 50,000/uL
Measured: Day 24 of Treatment

Secondary outcomes (13)

Median Time Needed to Reach Platelet Count >= 50,000 /µL in Days
Defined as the average number of days from the first day of eltrombopag until the first of five consecutive days with platelet counts >= 50,000 /µL without a platelet transfusion. The time will be summarized using the Kaplan-Meier method and will use the logrank test and proportional hazards models.
Measured: up to 12 weeks
Median Days of Platelet Transfusions
Defined as the median number of days from the first day of eltrombopag until the patient stopped treatment. The time will be summarized using the Kaplan-Meier method and will use the log-rank test and proportional hazards models.
Measured: Up to 12 weeks
Rates of Clinically Significant Bleeding Events
The number of bleeding events experienced by patients during treatment including hematuria, gastrointestinal bleed (with or without requiring intervention, retroperitoneal bleeding, intra-cranial bleed, epistaxis not controlled by conservative measures and muscle or soft tissue hematomas.
Measured: Up to 12 weeks
Median Time to Absolute Neutrophil Recovery, Defined as > 500/uL
The average number of days patients take to reach a neutrophil count >500/ul as summarized using the Kaplan-Meier method and modeled using logrank test and proportional hazards.
Measured: Up to 12 weeks
Median Rise in Hemoglobin Level in Patients With Pretreatment Hemoglobin of < 8 g/dL
The median increase in hemoglobin levels in g/dL among patients with a starting hemoglobin level <8g/dL
Measured: Up to 12 weeks
Complete Response Rate
The percent of participants with a sustained improvement of platelet counts (independent of platelet transfusions) to ≥ 50,000 /µL lasting for at least 2 weeks.
Measured: Up to 12 weeks
Median Days to Attain Complete Response
The median number of days participants take to achieve a complete response as defined as a sustained improvement of platelet counts (independent of platelet transfusions) to ≥ 50,000 /µL lasting for at least 2 weeks.
Measured: Up to 12 weeks
Partial Complete Response Rate
The number of participants with a sustained improvement of platelet counts (independent of platelet transfusions) seen by at least a doubling of platelet count from the pretreatment thrombocytopenic level (defined as < 10000 /µL, ) or an absolute increase in platelet counts to between 30000 /µL and 50000 /µL, whichever is higher but not achieving complete response. Or if there is a need to restart eltrombopag due to drop in platelet count to below 50000 /µL following interruption of eltrombopag therapy after achieving platelet counts of > 100000 /µL on the drug.
Measured: Up to 12 weeks
Time to Initiation of Post-remission Therapy
The average number of days from the the beginning of treatment to the onset of post-remission therapy as summarized using the Kaplan-Meier method and calculated using the logrank test and proportional hazards models.
Measured: Up to 12 weeks
Rate of Refractory or Persistent Disease
The number of participants with presence of morphologic evidence of disease
Measured: Up to 12 weeks
Overall Survival (OS) - Percent of Participants Alive at Follow-up
OS is defined from the day of study registration until the last follow-up or death
Measured: at 28 days, at 6 months
Number of Participants With 3/4 Adverse Events Adverse Events, Determined According to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Incidence of grade 3/4 adverse events (AE), determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
For full list, see AE/serious adverse event (SAE) section
Measured: Up to 4 weeks after last dose of eltrombopag olamine
Disease-Free Survival
Calculated from the date of complete remission until relapse, the date of last follow-up, or other protocol-defined event
Measured: Up to 52 months

Timeline

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

14 Aug 20146 Jan 2019

First posted26 Feb 2014 (estimated)
Study start14 Aug 2014
Primary completion20 Oct 2018
Study completion6 Jan 2019

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 Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic SyndromeStudies of the same condition, open and under way.
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.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 31 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02071901
Sponsor's protocol ID: CASE4913
Other IDs: NCI-2014-00252
Status last verified: Apr 2026
First submitted: 24 Feb 2014
Last updated: 7 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No