Decitabine for High-Risk Sickle Cell Disease
This study is currently recruiting participants.
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
First received: June 16, 2011
Last updated: January 14, 2014
Last verified: November 2013
- 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.
- To test the safety and effectiveness of decitabine in increasing fetal hemoglobin levels and improving the symptoms of sickle cell disease.
- 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.
- 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.
Sickle Cell Disease
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||An Extended Phase II Study of Decitabine in Subjects With High Risk Sickle Cell Disease
Primary Outcome Measures:
- Absolute percent change in HbF level from baseline [ Time Frame: 3 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Crisis frequency [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
- Safety [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
- Efficacy [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||December 2016 (Final data collection date for primary outcome measure)
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.
|Ages Eligible for Study:
||18 Years and older
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
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
- 3 or more pain episodes per year requiring parenteral narcotics, OR
- 1 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).
Since the protocol targets an at risk population, and the tolerability and potential benefits of this approach have been suggested in off-label treatment of seriously ill SCD patients, the exclusion criteria are not overly stringent and are primarily directed at avoiding teratogenic risks.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01375608
|National Institutes of Health Clinical Center, 9000 Rockville Pike
|Bethesda, Maryland, United States, 20892 |
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org |
||Matthew M Hsieh, M.D.
||National Heart, Lung, and Blood Institute (NHLBI)
||National Institutes of Health Clinical Center (CC) ( National Heart, Lung, and Blood Institute (NHLBI) )
History of Changes
|Other Study ID Numbers:
|Study First Received:
||June 16, 2011
||January 14, 2014
||United States: Federal Government
Keywords provided by National Institutes of Health Clinical Center (CC):
Sickle Cell Disease
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on March 09, 2014
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Molecular Mechanisms of Pharmacological Action