Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia

Study Overview
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Brief Summary
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Thalassemia intermedia (TI) is an inherited blood disorder that can cause anemia due to low levels of hemoglobin. Decitabine is a medication that may be effective at increasing hemoglobin levels. This study will evaluate the safety and effectiveness of decitabine at increasing hemoglobin levels in people with TI.

Detailed Description
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Thalassemias are inherited blood disorders that are characterized by low levels of hemoglobin and healthy red blood cells, which can lead to anemia. There are many different types of thalassemias, and TI is one type. People with TI often have moderate to severe anemia and may have a shortened life span, organ damage, and a lower quality of life as a result of the disease. Decitabine is a medication used to treat people with diseases that affect bone marrow and blood cells. The medication may be an effective treatment for people with TI because it may have the ability to interact with a person's DNA and increase hemoglobin levels. Previous studies in people with anemia have shown that decitabine has increased hemoglobin levels in some participants. The purpose of this study is to evaluate the safety and effectiveness of decitabine at increasing hemoglobin levels in people with TI. This study will enroll people with TI. Following an 8-week screening period, participants will attend a baseline study visit, which will include a blood collection, pregnancy test, physical exam, and echocardiogram heart imaging procedure. Decitabine will be injected under the skin in the abdomen, thigh, or upper arm. Participants will be observed for a minimum of 30 minutes after the injection to assess pain or adverse reactions. Participants will then receive low doses of decitabine twice a week, on consecutive days, for 12 weeks. They will be closely monitored and dosages will be adjusted or stopped as needed. Every 2 weeks, participants will undergo a blood collection for safety testing. Every 4 weeks, participants will attend a study visit for a pregnancy test, physical exam, blood collection, and review of medication effects. Additionally, at the Week 12 visit, a repeat echocardiogram will occur. During Weeks 12 to 24, participants will not receive decitabine injections but will attend monthly study visits for repeat testing. Study researchers will contact participants by phone every 3 months during Year 1 and then every 6 months for the duration of the study to collect long-term survival and medical information.

Official Title
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A Phase IIA Study of Subcutaneous 5-aza-2'- Deoxycytidine (Decitabine) in Patients With Thalassemia Intermedia

Conditions
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Thalassemia

Intervention / Treatment
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* Drug: Decitabine (USAN, INN)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Beta-thalassemia and beta thalassemia-hemoglobin E (HbE), as confirmed by DNA testing Transfusion independent for at least 120 days before study entry Red blood cell folate levels above the lower limit of normal Exclusion Criteria: Absolute neutrophil count (ANC) less than 2000/mm3 in the 8 weeks before study entry or a history of chronic neutropenia, defined as an ANC less than 2000/mm3 Platelet count less than 100,000/mm3 or greater than 1,000,000/mm3 in the 8 weeks before study entry Family history of an inherited disease resulting in low ANC or bone marrow failure Serum creatinine level greater than 2 mg/dL in the 8 weeks before study entry Evidence of liver disease, as defined by one or more of the following conditions: Alanine aminotransferase (ALT) level greater than 3 times the upper limit of normal in the 8 weeks before study entry Serum albumin level less than 3 g/dL in the 8 weeks before study entry Evidence of cirrhosis on liver biopsy obtained in the 6 months before study entry Approaching death; has concurrent liver, kidney, cardiac, or metabolic disease; or has any disease of such severity that death within 7 to 10 days of study entry is likely Pregnant, planning to become pregnant, or breastfeeding Sexually active female of childbearing potential who is unwilling to use at least two acceptable methods of contraception, as determined by the investigator Sexually active male whose partner is of child-bearing potential and who is unwilling to use at least two acceptable methods of contraception, as determined by the investigator, during and for 2 months after decitabine treatment Diagnosed with cancer (except non-melanoma skin cancer) in the 5 years before study entry. In particular, suspicion or evidence of myelodysplastic syndrome (MDS) on clinically indicated bone marrow aspirate or a family history of MDS or concurrent leukemia HIV infection Not expected to be able to complete 24 weeks of study follow-up Currently being treated with any experimental or fetal hemoglobin modulating agent Current participation in any other studies of investigational drugs or devices Unable to comply with study medication regimen Any condition, which in the opinion of the investigator, would place the individual at undue risk if treated with twice-weekly low-dose decitabine for 12 weeks

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive injected decitabine for 12 weeks. | Drug: Decitabine (USAN, INN)<br>* Participants will receive 0.2 mg/kg of decitabine subcutaneously twice a week for 12 weeks. The dose will be reduced for toxicities as needed. The maximum dose of decitabine to be given will be 0.2 mg/kg.<br>* Other names: Dacogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Evaluable Patients With an Increase From Baseline in Hemoglobin (Hb) of ≥1.5 g/dL |  | up to 12 weeks | 
| Change in Total Hemoglobin (Hb) From Baseline to Peak (the Follow-up Time Point With the Highest Value) |  | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Absolute Fetal Hemoglobin (HbF) From Baseline to Peak (the Follow-up Time Point With the Highest Value) |  | up to 12 weeks | 
| Change in Indirect Bilirubin From Baseline to Nadir (the Follow-up Time Point With the Lowest Value) |  | up to 12 weeks | 
| Change in Serum Lactate Dehydrogenase (LDH) From Baseline to Nadir (the Follow-up Time Point With the Lowest Value) |  | up to 12 weeks | 
| Change in Absolute Reticulocyte Count From Baseline to Nadir (the Follow-up Time Point With the Lowest Value) |  | up to 12 weeks | 
| Change in Erythropoietin Levels From Baseline to Nadir (the Follow-up Time Point With the Lowest Value) |  | up to 12 weeks | 
| Change in Platelet Count From Baseline to Peak (the Follow-up Time Point With the Highest Value) |  | up to 12 weeks | 
| Change in Neutrophil Counts From Baseline to Nadir (the Follow-up Time Point With the Lowest Value) |  | up to 12 weeks | 
| Change in Red Blood Cell (RBC) Deformability From Baseline to Peak (the Follow-up Time Point With the Highest Value) | Deformability was assessed by ektacytometry. Normal RBC have maximal deformability, measurable by osmotic ektacytometry, at isotonicity (290 mosmol). A decrease on the Deformability Index (measured in arbitrary units) corresponds to an impairment in the cell membrane's ability to alter its shape under stress. | up to 12 weeks | 
| Change in Percentage of Red Blood Cell (RBC) Hb Concentration From Baseline to Peak (the Follow-up Time Point With the Highest Value) |  | up to 12 weeks | 
| Change in Percentage of Annexin-positive Cells From Baseline to Nadir (the Follow-up Time Point With the Lowest Value) |  | up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thalassemia Intermedia