ThalassemiaPhase 2NCT00661726
Evaluating the Safety and Effectiveness of Decitabine in People With Thalassemia Intermedia
A Phase 2 study testing Decitabine (USAN, INN) in people with Thalassemia, run by Carelon Research at 3 sites in 2 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thalassemia
- What is being tested?
- Decitabine (USAN, INN)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 3 sitesin 2 countries
- Study dates
- Jan 2008to Sep 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United States2 sites
Children's Hospital and Research Center at Oakland
Oakland, California, 94609
Children's Hospital Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: A Phase IIA Study of Subcutaneous 5-aza-2'- Deoxycytidine (Decitabine) in Patients With Thalassemia Intermedia
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.
Read the detailed description
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.
- Conditions
- Thalassemia
- Being tested
- Decitabine (USAN, INN)
- Keywords
- Thalassemia Intermedia
- Medical subject headings
- Thalassemia, beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Decitabine (USAN, INN)Drug
Also called 5-aza-2'-deoxycytidine (NCS 127716), DAC, 5-Aza-CdR, Deoxyazacytidine
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.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive injected decitabine for 12 weeks. Receives: Drug: Decitabine (USAN, INN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Evaluable Patients With an Increase From Baseline in Hemoglobin (Hb) of ≥1.5 g/dL
Measured: up to 12 weeks
Change in Total Hemoglobin (Hb) From Baseline to Peak (the Follow-up Time Point With the Highest Value)
Measured: up to 12 weeks
Secondary outcomes (10)
Change in Absolute Fetal Hemoglobin (HbF) From Baseline to Peak (the Follow-up Time Point With the Highest Value)
Measured: up to 12 weeks
Change in Indirect Bilirubin From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Measured: up to 12 weeks
Change in Serum Lactate Dehydrogenase (LDH) From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Measured: up to 12 weeks
Change in Absolute Reticulocyte Count From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Measured: up to 12 weeks
Change in Erythropoietin Levels From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Measured: up to 12 weeks
Change in Platelet Count From Baseline to Peak (the Follow-up Time Point With the Highest Value)
Measured: up to 12 weeks
Change in Neutrophil Counts From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Measured: 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.
Measured: 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)
Measured: up to 12 weeks
Change in Percentage of Annexin-positive Cells From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Measured: up to 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2008 (estimated)
- Study startJan 2008
- Primary completionMay 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ThalassemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Carelon Research
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- Nancy Olivieri, MD, Study chair, University Health Network/Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00661726
- Sponsor's protocol ID
- 569
- Other IDs
- U01HL065238, 68,995
- Status last verified
- Feb 2014
- First submitted
- 16 Apr 2008
- Last updated
- 25 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Olivieri NF, Saunthararajah Y, Thayalasuthan V, Kwiatkowski J, Ware RE, Kuypers FA, Kim HY, Trachtenberg FL, Vichinsky EP; Thalassemia Clinical Research Network. A pilot study of subcutaneous decitabine in beta-thalassemia intermedia. Blood. 2011 Sep 8;118(10):2708-11. doi: 10.1182/blood-2011-03-341909. Epub 2011 Jun 23.
PubMed 21700776
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IIA Study of Subcutaneous 5-aza-2'- Deoxycytidine (Decitabine) in Patients With Thalassemia Intermedia
- ClinicalTrials.gov ID
- NCT00661726
- Acronym / sponsor ID
- 569
- Conditions
- Thalassemia
- Keywords
- Thalassemia Intermedia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Carelon ResearchUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2008
- Primary completion
- May 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 18 Apr 2008 (estimated)
- Results
- Posted 8 Apr 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Decitabine (USAN, INN)Participants will receive injected decitabine for 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (19 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Decitabine (USAN, INN)Also: 5-aza-2'-deoxycytidine (NCS 127716), DAC, 5-Aza-CdR, DeoxyazacytidineParticipants 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. | Drug | 1 |
Primary outcome
Number of Evaluable Patients With an Increase From Baseline in Hemoglobin (Hb) of ≥1.5 g/dL
Time frame: up to 12 weeks
Change in Total Hemoglobin (Hb) From Baseline to Peak (the Follow-up Time Point With the Highest Value)
Time frame: up to 12 weeks
10 secondary outcomes
Change in Absolute Fetal Hemoglobin (HbF) From Baseline to Peak (the Follow-up Time Point With the Highest Value)
Time frame: up to 12 weeks
Change in Indirect Bilirubin From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Time frame: up to 12 weeks
Change in Serum Lactate Dehydrogenase (LDH) From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Time frame: up to 12 weeks
Change in Absolute Reticulocyte Count From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Time frame: up to 12 weeks
Change in Erythropoietin Levels From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Time frame: up to 12 weeks
Change in Platelet Count From Baseline to Peak (the Follow-up Time Point With the Highest Value)
Time frame: up to 12 weeks
Change in Neutrophil Counts From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Time frame: up to 12 weeks
Change in Red Blood Cell (RBC) Deformability From Baseline to Peak (the Follow-up Time Point With the Highest Value)
Time frame: 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)
Time frame: up to 12 weeks
Change in Percentage of Annexin-positive Cells From Baseline to Nadir (the Follow-up Time Point With the Lowest Value)
Time frame: up to 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21700776Olivieri NF, Saunthararajah Y, Thayalasuthan V, Kwiatkowski J, Ware RE, Kuypers FA, Kim HY, Trachtenberg FL, Vichinsky EP; Thalassemia Clinical Research Network. A pilot study of subcutaneous decitabine in beta-thalassemia intermedia. Blood. 2011 Sep 8;118(10):2708-11. doi: 10.1182/blood-2011-03-341909. Epub 2011 Jun 23.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Nancy Olivieri, MD study chair
University Health Network/Toronto General Hospital
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Decitabine (USAN, INN) in people with Thalassemia, run by Carelon Research at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Evaluable Patients With an Increase From Baseline in Hemoglobin (Hb) of ≥1.5 g/dL (time frame: up to 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00661726, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2014.