Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT01550185 | Terminated Phase 1

• 2 other identifiers: I 206111NCI-2012-00215
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to find out the highest safe dose and examine the side effects and effectiveness of eltrombopag olamine in patients with acute myeloid leukemia (AML) treated with chemotherapy that have not responded to previous therapy or have suffered a relapse

Conditions

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); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• MTD and tolerability of eltrombopag olamine in patients with AML, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4

  Up to day 15

• Platelet count recovery to >= 100 x 10^9/L when eltrombopag olamine is administered following high dose cytarabine and mitoxantrone for the treatment of AML patients

  Up to 9 weeks

Secondary Outcomes (3)

• Platelet recovery to >= 100 x 10^9/L and platelet response, assessed based on a modified International Working Group Consensus Criteria for hematologic improvement

  Up to 9 weeks

• Platelet response based on a modified International Working Group Consensus Criteria for hematologic improvement

  Up to 9 weeks

• Platelet transfusion requirements

  Up to 9 weeks

Study Arms (1)

Treatment (eltrombopag olamine)

EXPERIMENTAL

Patients receive eltrombopag olamine PO QD from day 1 up to day 62. Treatment continues for up to 9 weeks in the absence of disease progression or unacceptable toxicity.

Drug: eltrombopag olamine; Procedure: standard follow-up care

Interventions

eltrombopag olamine DRUG

Given PO

Also known as: Promacta, SB 497115, SB-497115, SB497115

Treatment (eltrombopag olamine)

standard follow-up care PROCEDURE

Receive standard care

Treatment (eltrombopag olamine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed/refractory AML patients who received standard of care cytarabine and mitoxantrone as their chemotherapy regimen
• Patients must either have Grade 4 thrombocytopenia (platelet counts \< 25 x 10\^9/L) due to chemotherapy unless transfusion within 24-72 hours
• Current systemic treatment for AML, with the exception of granulocyte colony-stimulating factor (G-CSF) must have been discontinued at least 7 days prior to entry into the study; in addition:
• At least 4 weeks before Day 1 for interleukin (IL)-11 (oprelvekin)
• At least 8 weeks before Day 1 for antithymocyte/antilymphocyte globulin
• Patients with a prior stem cell transplant (SCT) must have failed the SCT
• Patients must have documented hypoplasia from the bone marrow aspiration and biopsy 14 days +/- 2 days from the initiation of cytarabine treatment schedule (defined as \< 5% blasts and \< 20% cellularity)
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\< 2
• Patient is able to understand and comply with protocol requirements and instructions
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) except for Gilbert syndrome or cases clearly not indicative of inadequate organ function, i.e., elevation of indirect (hemolytic) bilirubin in the absence of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormality
• ALT and AST =\< 3 x ULN
• Creatinine =\< 1.5 x ULN
• Patient is practicing an acceptable method of contraception (documented in chart); female patients (or female partners of male patients) must either be non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal \> 1 year), or of childbearing potential and use 1 of the following highly effective methods of contraception (i.e., Pearl Index \< 1.0%) from 2 weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
• Complete abstinence from intercourse
• Intrauterine device (IUD)

You may not qualify if:

• Patients with a diagnosis of acute promyelocytic leukemia
• Patients with a QTcF \> 450 msec (QTcF \> 480 msec for patients with Bundle Branch Block)
• AML patients with persistent disease from the recent treatment defined as \> 5% blast and/or \> 20% cellularity and reported as persistent residual disease by a pathological report of the patient's bone marrow biopsy 14 days +/- 2 days from the initiation of cytarabine
• Patients with known thrombophilic risk factors; exception: patients for whom the potential benefits of participating in the study outweigh the potential risks of thromboembolic events, as determined by the investigator
• 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
• Patients with known active hepatitis B, hepatitis C, or seropositive human immunodeficiency virus (HIV); testing is not required in the absence of clinical suspicion
• Patients with liver cirrhosis (as determined by the investigator)
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to eltrombopag or excipient that contraindicates the patients' participation
• Patients of East Asian ancestry (i.e., Chinese, Japanese, Taiwanese, or Korean)
• Patients with pre-existing cardiovascular disease (including congestive heart failure, New York Heart Association \[NYHA\] Grade III-IV), or arrhythmia known to increase the risk or thromboembolic events (e.g., atrial fibrillation)
• Unwilling or unable to follow protocol requirements
• Any condition which, in the Investigator's opinion, deems the patient an unsuitable candidate to receive study drug
• No aspirin (ASA) or nonsteroidal antiinflammatory drugs (NSAIDS) administration

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• GlaxoSmithKline: collaborator

Study Sites (2)

Emory University, Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Leukemia, Basophilic, Acute; Leukemia, Eosinophilic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Study Officials

• Wetzler Meir

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2012
• First Posted: March 9, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 22, 2022

Record last verified: 2022-07

Locations

US (2)