Eltrombopag With Decitabine in Advanced Myelodysplastic Syndrome (MDS)

NCT02010645 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 2013-0590NCI-2014-01276
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if eltrombopag given in combination with decitabine can help to control advanced MDS. The safety of this study drug combination will also be studied.

Conditions

Leukemia

Keywords

Leukemia; Advanced Myelodysplastic Syndrome; MDS; Intermediate-2 Myelodysplastic Syndrome; High-Risk Myelodysplastic Syndrome; Chronic myelomonocytic leukemia; CMML; Eltrombopag; Promacta; Decitabine; Dacogen

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The primary endpoint is the overall response rate (ORR) based on the IWG-2006 criteria, which includes complete remission (CR), partial remission (PR), and hematologic improvement (HI).

  28 days

Study Arms (1)

Eltrombopag + Decitabine

EXPERIMENTAL

Starting dose of Eltrombopag is 100 mg by mouth daily for each 28 day cycle. East Asians will start at 50 mg by mouth daily for each 28 day cycle. Starting dose of Decitabine is 20 mg/m2 by vein on Days 1-5 for each 28 day cycle.

Drug: Eltrombopag; Drug: Decitabine

Interventions

Eltrombopag DRUG

Starting dose of Eltrombopag is 100 mg by mouth daily for each 28 day cycle. East Asians will start at 50 mg by mouth daily for each 28 day cycle.

Also known as: Promacta

Eltrombopag + Decitabine

Decitabine DRUG

Starting dose of Decitabine is 20 mg/m2 by vein on Days 1-5 for each 28 day cycle.

Also known as: Dacogen

Eltrombopag + Decitabine

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) and chronic myelomonocytic leukemia (CMML) with at least 10% bone marrow blasts by World Health Organization (WHO) classification are eligible.
• Advanced MDS by virtue of intermediate-2 or high-risk MDS by IPSS score, or high or very-high risk by IPSS-R.
• Platelet count \</= 100 x 10\^9/L at baseline
• 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 ALT or AST \</= 3x the laboratory ULN.
• Serum creatinine \</= 2.5x upper limit of normal
• Subjects must be \>/= 18 years of age at the time of informed consent
• 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).

You may not qualify if:

• Subjects with any prior exposure to a thrombopoietin-receptor agonist
• Prior hypomethylating agent treatment for MDS
• 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
• 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.
• Subjects with liver cirrhosis (as determined by the investigator)
• Subjects with hypersensitivity to study drugs or their excipients.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• GlaxoSmithKline: 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; Leukemia, Myelomonocytic, Chronic

Interventions

eltrombopag; Decitabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Courtney DiNardo, MD/Associate Professor
• Organization: The University 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2013
• First Posted: December 13, 2013
• Study Start: March 1, 2014
• Primary Completion: January 2, 2019
• Study Completion: January 2, 2019
• Last Updated: January 2, 2020
• Results First Posted: January 2, 2020

Record last verified: 2019-12

Locations

US (1)