Eltrombopag in Myelodysplastic Syndrome (MDS) Patients With Thrombocytopenia

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01286038
First received: January 27, 2011
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to evaluate the safety and efficacy of eltrombopag in people who have myelodysplastic syndrome (MDS) with thrombocytopenia who have progressed or are resistant to decitabine or azacitidine. (These are the only 2 drugs approved by the U.S. Food and Drug Administration [FDA] which can improve platelet counts). The investigators (the study doctor, study staff, and sponsor) want to find out what effects, good or bad, eltrombopag (study drug) may have on people with low platelet counts due to MDS. The investigators will also be testing how well eltrombopag may work at different doses in these diseases.


Condition Intervention Phase
Myelodysplastic Syndrome (MDS)
Thrombocytopenia
Drug: Eltrombopag
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Eltrombopag in Myelodysplastic Syndrome (MDS) Patients With Thrombocytopenia Who Progressed or Are Resistant to Hypomethylating Agents

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Determine the maximum tolerated dose (MTD) of eltrombopag for the treatment of thrombocytopenia in participants with MDS who have either progressed or are resistant to Hypomethylating Agents (HMTA). The MTD is defined as the highest dose where less than 33% of participants experience a drug related predefined dose limited toxicity (DLT).


Secondary Outcome Measures:
  • Number of Participants with Complete or Major Platelet Response [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Proportion of participant achieving a complete or major platelet response utilizing International Working Group (IWG) 2006 response criteria and duration of platelets response.

  • Number of Participants Achieving a Platelets Transfusion Response [ Time Frame: 24 months ] [ Designated as safety issue: No ]
    Proportion of participants achieving a platelets transfusion response.

  • Number and Severity of Bleeding Events [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
    The incidence and severity of bleeding events, measured using the World Health Organization (WHO) Bleeding Scale, during the treatment and 4 week follow-up periods for eltrombopag.

  • Number of Participants with Overall Survival(OS) [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    To evaluate the effect of eltrombopag on overall survival (OS).


Estimated Enrollment: 57
Study Start Date: March 2011
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Eltrombopag Treatment
Phase I: Dose Escalation. Phase II: Treatment at Maximum Tolerated Dose (MTD)
Drug: Eltrombopag
In Stage 1 the best dose of eltrombopag will be found to take into Stage 2, which will treat 15 participants at this dose.
Other Name: Promacta®

Detailed Description:

Study drug will be administered on an outpatient basis. The study is divided into two parts: in Stage 1 the best dose of eltrombopag will be found to take forward to Stage 2. In Stage 1 of the study, small groups of participants will be enrolled in steps. The first group will be given a dose of 50 mg per day of study drug for 8 weeks. If these participants have few or manageable side effects, the next group of participants enrolled will receive a higher dose of study drug (100 mg per day for 8 weeks). This increase in doses with groups of participants will continue until the study doctor finds the highest dose of study drug that can be given without causing severe or unmanageable side effects up to a 300 mg daily dose. Stage 2 will include 15 participants at the best dose based on the Stage 1 part of the study. The participant's dose may be adjusted to a lower or higher dose based upon their platelet count, which will be determined by the study doctor. Eltrombopag will be supplied by a company called GlaxoSmithKline as white to off-white, round film coated tablets containing eltrombopag equivalent to 12.5mg, 25mg, 50 mg, 75 mg and 100 mg of eltrombopag.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed diagnosis of MDS using the World Health Organization (WHO) classification or a diagnosis of WHO Myelodysplastic/ Myeloproliferative Neoplasm (MDS/MPN) or MDS refractory anemia with excess blast in transformation (RAEB-t) by French American British (FAB) classification (AML with 20-30% myeloblasts by WHO classification).
  • All prognostic risk groups according to the International Prognostic Scoring System (IPSS) and MD Anderson Risk Model
  • At least one prior HMTA treatment with either azacitidine or decitabine and subsequent loss of response to HMTA, progression while on HMTA, or no response to HMTA, defined as failure to achieve at least HI after 4 cycles of treatment
  • The mean of the two platelet counts taken within 1 month prior to dosing must be ≤50 x 10^9/L. Platelets counts must reflect pre-transfusion trough results or be obtained no sooner than 1 week after platelet transfusion to assure stable baseline platelet count. The platelet count obtained should be outside the expected nadir of prior therapies.
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (Karnofsky >60%
  • Adequate liver function, as evidenced by total serum bilirubin ≤ 1.5 times the upper limit of normal (patients with Gilbert's disease are eligible, provided intermittent indirect hyperbilirubinemia), aspartic transaminase (AST) or alanine transaminase (ALT) ≤ 3 times the upper limit of normal (ULN).
  • A serum creatinine concentration ≤ 2 x ULN
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Clinically significant bleeding within 4 weeks of screening defined as any grade 3 or grade 4 bleeding by WHO Bleeding Scale or any gastrointestinal (GI) bleeding or intracranial hemorrhage
  • Splenic enlargement extending >8 cm below the left costal margin
  • Myelodysplastic syndrome with fibrosis (MF 3)
  • Received Anti-Thymocyte Globulin (ATG) within 6 months of screening
  • Received immunomodulating agents, histone deacetylase inhibitors, cyclosporine, or mycophenolate within 4 weeks of screening
  • History of treatment with eltrombopag, romiplostim or other thrombopoietin receptor (TPO-R) agonists
  • Concurrent use of granulocyte colony-stimulating factor (G-CSF) except for the short-term management of neutropenic infection. Stable doses of erythropoietin stimulating agents or corticosteroids that were being administered prior to screening are allowed.
  • Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study medication.
  • Pregnant or breast feeding
  • Current alcohol or drug abuse
  • Known Hepatitis B or Hepatitis C infection or liver cirrhosis
  • Uncontrolled current illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • At eltrombopag dose levels 200 mg and above cohorts, participants with a QT corrected for heart rate (QTc) > 480 msec at screening, if other drugs known to cause prolonged QT are stopped an EKG documenting QTc below 480 msec is required.
  • History of metastatic malignancy in the preceding 2 years
  • Known Human Immunodeficiency Virus (HIV) positive patients. These patients are excluded because they may have morphologic dysplasia which mimics MDS but is not true MDS Tand thrombocytopenia could be multifactorial secondary to HIV infection or to medications.
  • Receiving, or planning to receive, any of the medications listed in the Prohibited Medications section during conduct of the study.
  • East Asian patients (Chinese, Japanese, Taiwanese, and Korean ancestry) are excluded during stage I of the study (dose escalation phase) due to the different pharmacogenomics in this patient population.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01286038

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: William Prada    813-745-3323    william.prada@moffitt.org   
Principal Investigator: Rami Komrokji, M.D.         
Sub-Investigator: Celeste Bello, M.D.         
Sub-Investigator: Jeffrey Lancet, M.D.         
Sub-Investigator: Alan List, M.D.         
Sub-Investigator: Eric Padron, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
GlaxoSmithKline
Investigators
Principal Investigator: Rami Komrokji, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01286038     History of Changes
Other Study ID Numbers: MCC-16523
Study First Received: January 27, 2011
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
platelets

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Thrombocytopenia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Blood Platelet Disorders

ClinicalTrials.gov processed this record on July 23, 2014