- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01685515
Study of Decitabine and Tetrahydrouridine (THU) in Patients With Sickle Cell Disease
Phase 1 Study of Oral Decitabine and Tetrahydrouridine (THU) in Patients With High Risk Sickle Cell Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60612
- University of Illinois at Chicago
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18 years or older.
- Written, informed consent provided by the subject before study entry.
- Confirmed Sickle Cell Disease (SCD) (SS, S-b0-thalassemia, S-b+-thalassemia or SC on hemoglobin electrophoresis).
Symptomatic SCD while on 6 months of HU OR symptomatic SCD and intolerant of HU (unable or unwilling to take HU due to hematological or other toxicities). Symptomatic SCD is defined as having one of following:
- Fetal Hemoglobin (HbF) <5%, OR
- 3 or more pain episodes per year requiring parenteral narcotics, OR
- 1 or more acute chest syndrome episodes, OR
- Hemoglobin <9 g/dL and absolute reticulocyte count <250,000/mm3.
- Subject is in his/her steady state and not amidst any acute complication due to SCD (i.e., hospitalization, acute pain, or acute chest syndrome in the past 14 days).
- Regular compliance with comprehensive care and previous therapy.
Exclusion Criteria:
- Inability to give informed consent.
- Experienced severe sepsis or septic shock within the previous 12 weeks.
- Last HU dose was ingested within the previous 4 weeks.
- Currently pregnant or breast-feeding.
- Alanine aminotransferase (ALT) greater than or equal to two times (2X) the upper limit of normal or albumin <2.0 mg/dL or direct (conjugated) bilirubin greater than or equal to 1.5 mg/dl.
- Serum creatinine >2.9 mg/dL and calculated creatinine clearance <30 mL/min.
- Platelet count >800 x 109/L.
- Absolute neutrophil count <1.5 x 109/L.
Female of active childbearing potential who is unwilling to use at least one of the two following forms of birth control:
(i) not having heterosexual sexual contact beginning at the screening visit and continuing until 4 weeks after the last dose of THU-decitabine OR (ii) intrauterine device (IUD).
- Sexually active male who is unwilling to use a condom when engaging in any sexual contact with a female with child-bearing potential, beginning at the screening visit and continuing until 4 weeks after taking the last dose of THU-decitabine. This requirement applies also to males who have had a successful vasectomy.
- Altered mental status or recurrent seizures requiring anti-seizure medications.
- Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely.
- Concurrent diagnosis of malignancy including myelodysplastic syndromes (MDS), leukemia, or an abnormal karyotype.
- Vitamin-B12, folate, or iron deficient (until corrected).
- New York Heart Association (NYHA) class III/IV status.
- Eastern Co-operative Oncology Group (ECOG) performance status greater than or equal to 3.
- Participant is on chronic transfusion therapy (e.g., for history of Transient Ischemic Attack (TIA) or stroke) and medically contraindicated to discontinue transfusions (unless multiple allo-antibodies prevent the patient from getting transfusions as scheduled).
- Known history of illicit drug or alcohol abuse within the past 12 months.
- Other experimental or investigational drug therapy in the past 28 days.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: RANDOMIZED
- Interventional Model: PARALLEL
- Masking: SINGLE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
PLACEBO_COMPARATOR: Placebo
|
Plain water will be dispensed at a similar volume and in the same containers as study drug.
The water placebo has a similar appearance and taste to the study drug, since the study drug is highly diluted in water.
Other Names:
|
EXPERIMENTAL: Oral Decitabine and Tetrahydrouridine
|
Oral Decitabine and Oral Tetrahydrouridine (THU) given 1-2 hours apart on 2 consecutive days over 8 weeks
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Non-hematologic toxicity
Time Frame: 12 weeks
|
Toxicities will be evaluated on a weekly basis and will be classified according to their grade and relationship to study treatment.
Chi-square testing will be employed to examine the difference in number of patients with grade 3 or greater non-hematologic toxicity between treatment and placebo groups.
|
12 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Yogen Saunthararajah, MD, The Cleveland Clinic
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Hematologic Diseases
- Genetic Diseases, Inborn
- Anemia
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Hemoglobinopathies
- Anemia, Sickle Cell
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Decitabine
- Tetrahydrouridine
Other Study ID Numbers
- CASE 10Z11
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Sickle Cell Disease
-
Klein Buendel, Inc.National Institute on Minority Health and Health Disparities (NIMHD); Hilton...CompletedSickle Cell Disease | Sickle Cell Anemia in Children | Sickle Cell Thalassemia | Sickle Cell SC DiseaseUnited States
-
Nova Laboratories LimitedCompletedSickle Cell Disease | Sickle Cell Hemoglobin C | Sickle Cell-beta-thalassemia | Sickle-Cell; Hemoglobin Disease, ThalassemiaUnited Kingdom, Jamaica
-
SangartCompletedSickle Cell Disease | Anemia, Sickle Cell | Sickle Cell Anemia | Hemoglobin SC Disease | Sickle Cell Disorders | Sickle Cell Hemoglobin C DiseaseUnited Kingdom, France, Jamaica, Lebanon
-
SangartWithdrawnSickle Cell Disease | Anemia, Sickle Cell | Sickle Cell Anemia | Hemoglobin SC Disease | Sickle Cell Disorders | Sickle Cell Hemoglobin C DiseaseFrance, United Kingdom, Netherlands, Turkey, Bahrain, Belgium, Brazil, Lebanon, Qatar
-
University of British ColumbiaCompletedSickle Cell Disease | Beta-Thalassemia | Sickle Cell Trait | Sickle Cell-Beta Thalassemia | Sickle Cell-SS DiseaseCanada, Nepal
-
Sidney Kimmel Cancer Center at Thomas Jefferson...National Heart, Lung, and Blood Institute (NHLBI)TerminatedSickle Cell Anemia | Sickle Cell-hemoglobin C Disease | Sickle Cell-β0-thalassemiaUnited States
-
University of RegensburgRecruitingSickle Cell Disease | Sickle Cell Anemia | Sickle Cell Disorders | HbS Disease | Hemoglobin S Disease | Sickling Disorder Due to Hemoglobin SGermany, Austria
-
Centre Hospitalier Intercommunal CreteilRecruitingSickle-Cell Disease Nos With CrisisFrance
-
HemaQuest Pharmaceuticals Inc.TerminatedSickle Cell Disease | Sickle Cell Anemia | Sickle Cell Disorders | Hemoglobin S Disease | Sickling Disorder Due to Hemoglobin SUnited States, Lebanon, Egypt, Canada, Jamaica
-
HemaQuest Pharmaceuticals Inc.CompletedSickle Cell Disease | Sickle Cell Anemia | Sickle Cell Disorders | Hemoglobin S Disease | Sickling Disorder Due to Hemoglobin SUnited States, Lebanon, Canada, Egypt, Jamaica
Clinical Trials on Oral Decitabine and Tetrahydrouridine
-
Novo Nordisk A/SRecruitingSickle Cell DiseaseSpain, United States, United Kingdom, Canada, Italy, India, Turkey, Greece, South Africa, France, Lebanon
-
National Cancer Institute (NCI)TerminatedCarcinoma, Non-Small-Cell Lung | Non-Small Cell Lung Cancer | Lung Cancer | Carcinoma, Esophageal | Malignant Pleural MesotheliomasUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)Active, not recruitingLung Cancer | Non-small Cell Lung CancerUnited States
-
National Cancer Institute (NCI)TerminatedBreast Neoplasms | Head and Neck Neoplasms | Lung Neoplasms | Urinary Bladder NeoplasmsUnited States
-
Yogen SaunthararajahCompletedT-cell Lymphoma | Indolent B-cell Lymphoma | Aggressive B-cell Lymphoma | Non-Hodgkin's LymphomasUnited States
-
EpiDestiny, Inc.Worldwide Clinical TrialsRecruiting
-
EpiDestiny, Inc.Completed
-
National Cancer Institute (NCI)WithdrawnMelanoma | Sarcoma | Neoplasms, Germ Cell and Embryonal | Neoplasm Metastasis
-
Astex Pharmaceuticals, Inc.CompletedMyelodysplastic Syndrome | MDSUnited States, Canada
-
Yogen SaunthararajahCompletedMetastatic Pancreatic AdenocarcinomaUnited States