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

NCT01893372 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2013-0225NCI-2013-02252
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia

Keywords

Leukemia; Myelodysplastic syndrome; MDS; Overall response rate; ORR; Eltrombopag; Promacta; Hypomethylating Agent

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR)

  Overall response rate (ORR) based on the International Working Group (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. CR is Bone marrow of \</= 5% myeloblasts with normal maturation of cell lines, persistent dysplasia and a hemoglobin \>/= 11g/dl, platelets \>/= 100x10\^9/L, neutrophils \>/= 1.0x10\^9/L and 0% blasts. PR is the same as CR but bone marrow blasts decreased by \>/=50% but still 5% over pre-treatment. HI is described by the number of individually affected cell lines. (E = Erythroid, N = Neutrophils, P = Platelet). HI-E is a 2 gram increase in hemoglobin. HI-N is at least a 100% increase or an absolute increase of more than 500/mm\^3. HI-P is an absolute increase of 30/mm\^3 or a 50% increase

  After second 28 day cycle

• Overall Survival (OS)

  Overall Survival (OS) was measured from the time of study enrollment until death from any cause or fate of the last follow-up.

  Through study completion. Up to 3 years, 3 months.

Secondary Outcomes (2)

• Number of Participants Transforming From Myelodysplastic Syndrome (MDS) to Acute Myeloid Leukemia (AML)

  Up to 3 years, 3 months.

• Number of Participants Achieving a Platelet Response

  3 Years

Study Arms (2)

Eltrombopag

EXPERIMENTAL

Eltrombopag 200 mg by mouth daily in a 28 day cycle.

Drug: Eltrombopag

Eltrombopag + Hypomethylating Agent (HMA)

EXPERIMENTAL

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; Drug: Hypomethylating Agent (HMA)

Interventions

Eltrombopag DRUG

200 mg by mouth daily in a 28 day cycle.

Also known as: Promacta

Eltrombopag; Eltrombopag + Hypomethylating Agent (HMA)

Hypomethylating Agent (HMA) DRUG

The choice of HMA agent (e.g. azacitidine or decitabine) will be the HMA the patient has received prior to enrollment on study.

Eltrombopag + Hypomethylating Agent (HMA)

Eligibility Criteria

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

You may qualify if:

• Signed, informed consent must be obtained prior to any study specific procedures.
• 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.
• 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 International Working Group (IWG) (platelet count \< 100x10\^9/L, hemoglobin \<11g/L or Absolute Neutrophil Count (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.
• Platelet count \<100x10\^9/L
• Low, intermediate-1, intermediate-2 or High-risk category by International Prognostic Scoring System (IPSS)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• 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 Alanine Aminotransferase (ALT) or Aspartate Aminotransferase (AST) \</=3x the laboratory Upper Limit of Normal (ULN).
• Serum creatinine \</=2x upper limit of normal
• 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.
• 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).
• 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.

You may not qualify if:

• Subjects with any prior exposure to a thrombopoietin-receptor agonist
• 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
• Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary study procedures
• Active uncontrolled serious infection or sepsis at study enrollment
• Clinically significant gastrointestinal disorders that may interfere with absorption of drug.
• History of arterial thrombosis (i.e. stroke) in the past year
• History of venous thrombosis currently requiring anti-coagulation therapy
• 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
• Subjects with a QTc \> 480 msec (QTc \> 510 msec for subjects with Bundle Branch Block) at baseline
• 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes

Interventions

eltrombopag

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Results Point of Contact

• Title: Courtney DiNardo, MD/Associate Professor
• Organization: The Universtiy of Texas MD Anderson Cancer Center

CDiNardo@mdanderson.org

713-794-1141

Study Officials

• Courtney DiNardo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2013
• First Posted: July 9, 2013
• Study Start: October 1, 2013
• Primary Completion: January 6, 2019
• Study Completion: January 6, 2019
• Last Updated: February 18, 2020
• Results First Posted: February 18, 2020

Record last verified: 2020-02

Locations

US (1)