Decitabine for High-Risk Sickle Cell Disease

NCT01375608 | Completed Phase 2 Results

• 2 other identifiers: 11018411-H-0184
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• In sickle cell disease (SCD), the proteins in the red blood cells that carry oxygen do not behave normally. In parts of the body where there are low levels of oxygen or where oxygen is used more, the sickle hemoglobin proteins may change shape and stick together. This causes the red cells to clump, which reduces blood flow. This leads to even lower oxygen levels and causes damage and/or pain.
• One way to stop the red blood cells from sticking together is to increase the levels of fetal (baby or good ) hemoglobin. The good hemoglobin then takes the place of the sickle hemoglobin.
• Hydroxyurea is the only approved drug for SCD. But hydroxyurea works in only about two-thirds of people with SCD. Even in those cases it sometimes stops working over time.
• Researchers are interested in testing decitabine. The drug may help to increase fetal hemoglobin levels. But it has not yet been approved to treat SCD. Objectives: \- To test the safety and effectiveness of decitabine in increasing fetal hemoglobin levels and improving the symptoms of sickle cell disease. Eligibility: \- People at least 18 years of age who have sickle cell disease that has not improved after at least 6 months of hydroxyurea therapy. Those who cannot take hydroxyurea because of side effects may also participate. Design:
• Participants will be screened with a physical exam and medical history. They will also have blood and urine tests, a lung function test, and other tests as required.
• Participants will receive decitabine injections up to twice a week for 1 year. Depending on the response to treatments, the dose will remain the same or be reduced to once a week.
• Participants will be monitored with frequent blood tests and other studies as directed by the study doctors.
• After the study is completed, participants will go back to their usual sickle cell care. If decitabine has improved a participant's SCD, treatment may be continued under regular health coverage insurance if this can be arranged.

Conditions

Neutropenia; Sickle Cell Disease

Keywords

Neutropenia; Hemaglobin; Coagulation Disorders; Thrombocytosis; Red Blood Cells; Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• The Percentage Change in HbF Level From Baseline to the Average Over the Final 1 Month of Study.

  Final 1 month of study

Study Arms (1)

decitabine

OTHER

active treatment

Drug: Decitabine

Interventions

Decitabine DRUG

0.2mg/kg (range, 0.05-0.3 mg/kg) 1-2X/wk for a period of 48 weeks. Dose and frequency will be determined by hematologic toxicity and the achievement of an HbF level of greater the or equal to 20 percent.

decitabine

Eligibility Criteria

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

You may qualify if:

• Subjects who meet all of the following criteria are eligible for enrollment into the study:
• Age 18 years or older.
• Written, informed consent provided by the subject before study entry.
• Confirmed SCD (SS, S-beta (0)-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 tolerate HU due to hematological or other toxicities). Symptomatic SCD is defined as having one of following:
• HbF \<5 percent, OR
• or more pain episodes per year requiring parenteral narcotics, OR
• or more acute chest syndrome episodes, OR
• Hemoglobin \<9 degree g/dL and ARC less than or equal to 250,000/mm(3),
• Subject is in his/her steady state and not amidst any acute complication due to SCD.
• Willing to use 2 forms of contraception. Some acceptable combinations include male partner using condoms and female partner using oral contraceptives, male partner using condoms and female partner who had bilateral oophorectomy, male partner who had a vasectomy and female partner using injectable contraceptives (e.g. Depo Provera).

You may not qualify if:

• Subjects who meet any of the following criteria are disqualified from enrollment in the study:
• Inability to give informed consent.
• Experienced severe sepsis or septic shock within the previous 12 weeks.
• Last HU or erythropoietin dose obtained within the previous 4 weeks. Renal replacement doses of erythropoietin is allowed as decitabine would not be expected to exert a red cell and/or HbF response when there is no endogenous erythropoietin production.
• Participant is on chronic transfusion therapy (e.g., for history of TIA or stroke) and medically contraindicated to discontinue transfusions.
• Currently pregnant or breast-feeding.
• Sexually active female of childbearing potential (all females except those who are menopausal \[appropriate age and no period for more than 12 months\] or have had a hysterectomy and/or bilateral oophorectomy) who is unwilling to use at least 2 acceptable methods of contraception as determined by the investigators. The use of a condom by a male partner would be considered one acceptable method of contraception.
• Sexually active male whose partner is of child-bearing potential and who is unwilling to use at least 2 acceptable methods of contraception as determined by the investigators during treatment and for 8 weeks after the last dose of decitabine.
• Moribund or any concurrent disease (e.g., hepatic, renal, cardiac, metabolic) of such severity that death within 24 weeks is likely.
• Other experimental or investigational drug therapy in the past 28 days.
• Inability to bring ANC above 2 x 10(9) cells/L or platelet count less than 1,000 x 10(9) cells/L.
• For female participants: Not having heterosexual sexual contact starting 4 weeks before beginning to take decitabine and continuing until 4 weeks after the last dose of decitabine OR using TWO methods of birth control. One birth control method must be highly effective, such as an Intrauterine Device (IUD), birth control pills, Depo-Provera (medroxyprogesterone acetate) injections, or tying of the fallopian tubes. The other additional effective method of birth control can be use of a diaphragm or a condom by the male partner. Birth control should begin at the screening visit and continue until 4 weeks after the last dose of decitabine. These steps must be taken even if the patient has a history of infertility, unless the patient has had a hysterectomy or has not had periods for at least 24 months.
• For male participants: during decitabine treatment and 8 weeks after last dose of drug, a condom must be used when engaging in any sexual contact with a woman of child-bearing age, even in patients who have had a successful vasectomy.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• WATSON J. The significance of the paucity of sickle cells in newborn Negro infants. Am J Med Sci. 1948 Apr;215(4):419-23. doi: 10.1097/00000441-194804000-00008. No abstract available.

  PMID: 18107723 BACKGROUND

• CONLEY CL, WEATHERALL DJ, RICHARDSON SN, SHEPARD MK, CHARACHE S. Hereditary persistence of fetal hemoglobin: a study of 79 affected persons in 15 Negro families in Baltimore. Blood. 1963 Mar;21:261-81. No abstract available.

  PMID: 14022587 BACKGROUND

• Perrine RP, Pembrey ME, John P, Perrine S, Shoup F. Natural history of sickle cell anemia in Saudi Arabs. A study of 270 subjects. Ann Intern Med. 1978 Jan;88(1):1-6. doi: 10.7326/0003-4819-88-1-1.

  PMID: 619731 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Neutropenia; Anemia, Sickle Cell; Hemostatic Disorders; Thrombocytosis

Interventions

Decitabine

Condition Hierarchy (Ancestors)

Agranulocytosis; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Blood Platelet Disorders; Myeloproliferative Disorders; Bone Marrow Diseases

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: Dr Matthew Hsieh
• Organization: NIH, NHLBI, MCHB

matthewhs@nhlbi.nih.gov

301-402-7687

Study Officials

• Matthew M Hsieh, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: June 17, 2011
• Study Start: June 1, 2011
• Primary Completion: December 1, 2015
• Study Completion: February 1, 2016
• Last Updated: March 1, 2017
• Results First Posted: March 1, 2017

Record last verified: 2017-01

Locations

US (1)