Study of Decitabine and Tetrahydrouridine (THU) in Patients With Sickle Cell Disease

NCT01685515 | Completed Phase 1 DMC

• 1 other identifier: CASE 10Z11
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purposes of this study are to observe if oral tetrahydrouridine and decitabine can increase fetal hemoglobin levels and improve the symptoms of sickle cell disease, and to monitor how patient's bodies react to oral tetrahydrouridine and decitabine.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Non-hematologic toxicity

  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

Study Arms (2)

Oral Decitabine and Tetrahydrouridine

EXPERIMENTAL

Oral Decitabine and Tetrahydrouridine

Drug: Oral Decitabine and Tetrahydrouridine

Placebo

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Oral Decitabine and Tetrahydrouridine DRUG

Oral Decitabine and Oral Tetrahydrouridine (THU) given 1-2 hours apart on 2 consecutive days over 8 weeks

Also known as: Dacogen, 5-aza-2'-deoxycytydine, THU

Oral Decitabine and Tetrahydrouridine

Placebo DRUG

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.

Also known as: Water

Placebo

Eligibility Criteria

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

You may qualify if:

• 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
• or more pain episodes per year requiring parenteral narcotics, OR
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Yogen Saunthararajah: lead
• University of Illinois at Chicago: collaborator

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

Related Publications (1)

• Molokie R, Lavelle D, Gowhari M, Pacini M, Krauz L, Hassan J, Ibanez V, Ruiz MA, Ng KP, Woost P, Radivoyevitch T, Pacelli D, Fada S, Rump M, Hsieh M, Tisdale JF, Jacobberger J, Phelps M, Engel JD, Saraf S, Hsu LL, Gordeuk V, DeSimone J, Saunthararajah Y. Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study. PLoS Med. 2017 Sep 7;14(9):e1002382. doi: 10.1371/journal.pmed.1002382. eCollection 2017 Sep.

  PMID: 28880867 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Decitabine; Tetrahydrouridine; Water

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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; Uridine; Hydroxides; Alkalies; Inorganic Chemicals; Anions; Ions; Electrolytes; Oxides; Oxygen Compounds

Study Officials

• Yogen Saunthararajah, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Staff in the Department of Hematology and Oncology

Study Record Dates

• First Submitted: September 6, 2012
• First Posted: September 14, 2012
• Study Start: August 1, 2012
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: September 11, 2018

Record last verified: 2018-09

Locations

US (1)