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

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ClinicalTrials.gov Identifier: NCT01893372
Recruitment Status : Completed
First Posted : July 9, 2013
Last Update Posted : May 10, 2019
Sponsor:
Collaborators:
GlaxoSmithKline
Novartis
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to learn if eltrombopag can help to control MDS. The safety of this drug will also be studied.

Condition or disease Intervention/treatment Phase
Leukemia Drug: Eltrombopag Drug: Hypomethylating Agent (HMA) Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Eltrombopag With or Without Continuation of Hypomethylating Agent After Hypomethylating Agent Failure For Patients With Myelodysplastic Syndrome (MDS)
Actual Study Start Date : October 2013
Actual Primary Completion Date : January 6, 2019
Actual Study Completion Date : January 6, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Eltrombopag

Arm Intervention/treatment
Experimental: Eltrombopag
Eltrombopag 200 mg by mouth daily in a 28 day cycle.
Drug: Eltrombopag
200 mg by mouth daily in a 28 day cycle.
Other Name: Promacta

Experimental: 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.

Drug: Eltrombopag
200 mg by mouth daily in a 28 day cycle.
Other Name: Promacta

Drug: 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.




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: After second 28 day cycle ]
    Overall response rate (ORR) based on the 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed, informed consent must be obtained prior to any study specific procedures.
  2. Subjects with a histologically confirmed diagnosis of MDS by FAB criteria, including both MDS and RAEB-T (AML with 20-30% blasts and multilineage dysplasia) by World Health Organization (WHO) classification are eligible.
  3. Patients must have completed at least 4 cycles of hypomethylating agent therapy (e.g azacitidine or decitabine) with failure to achieve at least a partial response, or with the presence of ongoing cytopenias per IWG (platelet count < 100x10^9/L, hemoglobin <11g/L or ANC <1x10^9/L). Patients with progressive disease on HMA-therapy prior to this time point are also eligible at the time of documented progression. Therapy with decitabine analogs (i.e. SGI-110) will be considered as decitabine for the purposes of this study.
  4. Platelet count <100x10^9/L
  5. Low, intermediate-1, intermediate-2 or High-risk category by IPSS
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
  7. Adequate liver function, as evidenced by a serum bilirubin </=2x the ULN (except for patients with a confirmed diagnosis of Gilbert's Disease) and an ALT or AST </=3x the laboratory ULN.
  8. Serum creatinine </=2x upper limit of normal
  9. Subjects must be>/= 18 years of age at the time of informed consent, because no dosing or adverse event data are currently available on the use of eltrombopag in children.
  10. Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subject) must either be of non-childbearing potential (hysterectomy, bilateral oophorectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one 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); - Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide); - Male partner is sterile prior to entry into the study and is the only partner of the female; - Systemic contraceptives (combined or progesterone only).
  11. Patients must have recovered from acute toxicity (to grade 1 or less) of all previous therapy prior to enrollment. Treatment may start earlier if necessitated by the patient's medical condition (e.g. progressive disease) following discussion with the Investigator.

Exclusion Criteria:

  1. Subjects with any prior exposure to a thrombopoietin-receptor agonist
  2. Any prior or co-existing medical condition that in the investigator's judgment will substantially increase the risk associated with the subject's participation in the study
  3. Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
  4. Active uncontrolled serious infection or sepsis at study enrollment
  5. Clinically significant gastrointestinal disorders that may interfere with absorption of drug.
  6. History of arterial thrombosis (i.e. stroke) in the past year
  7. History of venous thrombosis currently requiring anti-coagulation therapy
  8. Unstable angina, congestive heart failure (New York Heart Association (NYHA) > Class II), uncontrolled hypertension (diastolic blood pressure > 100mmHg), or recent (within 1 year) myocardial infarction
  9. Subjects with a QTc > 480 msec (QTc > 510 msec for subjects with Bundle Branch Block) at baseline
  10. Pregnant or breast-feeding because there are no adequate and well-controlled studies of eltrombopag use in pregnancy and it is unknown whether eltrombopag is excreted in human milk.
  11. Subjects with known history of human immunodeficiency virus (HIV) or active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV), because eltrombopag is hepatically cleared, and underlying hepatic impairment may lead to an increased risk of hepatotoxicity. Eltrombopag has not been evaluated with combination antiretroviral regimens.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01893372


Locations
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United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
GlaxoSmithKline
Novartis
Investigators
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Principal Investigator: Courtney DiNardo, MD M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01893372     History of Changes
Other Study ID Numbers: 2013-0225
NCI-2013-02252 ( Registry Identifier: NCI CTRP )
First Posted: July 9, 2013    Key Record Dates
Last Update Posted: May 10, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Myelodysplastic syndrome
MDS
Overall response rate
ORR
Eltrombopag
Promacta
Hypomethylating Agent
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Decitabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors