Transfusion-dependent Beta-ThalassemiaPhase 3NCT06146478
Deciphering Effects of Thalidomide on Red Blood Cells in Transfusion Dependents Beta Thalassemia Patients
A Phase 3 study testing Thalidomide in people with Transfusion-dependent Beta-Thalassemia, run by Blood Care Clinic at 1 site in Pakistan.
Trial summary
The goal of this Non-Randomized Clinical Trial is to determine the effects of thalidomide on red blood cells in transfusion dependent beta thalassemia patients. The main aims of this study are: To determine the therapeutic effect of Thalidomide on hemoglobin. Read more about this study
- Who is it for?
- Ages 1 year to 18 years
- Conditions the study is for
- Transfusion-dependent Beta-Thalassemia
- What is being tested?
- Thalidomide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 sitePakistan
- Study dates
- 25 Jan 2022to 31 Oct 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 1 year to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosed transfusion dependent β-thalassemia patients
- Possess a verified pre transfusion Hb electrophoresis report performed at age≥ 6 months
Who cannot join
- Patients with active metabolic or systemic comorbidities
- Patients with autologous antibodies, AIHA or hypersplenism
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Deciphering Effects of Thalidomide on Red Blood Cells in Transfusion Dependents Beta Thalassemia Patients: A Pharmacodynamics and Pharmacogenetics Analysis
The goal of this Non-Randomized Clinical Trial is to determine the effects of thalidomide on red blood cells in transfusion dependent beta thalassemia patients. The main aims of this study are:
- To determine the therapeutic effect of Thalidomide on hemoglobin.
- To analyze association of different β- globin mutations with response to thalidomide in β-thalassemia patients.
- To analyze association of Single Nucleotide Polymorphisms (SNPS) of HBG2, BCL11A and HBS1L-MYB with response to thalidomide in β-thalassemia patients.
- To correlate GATA1 and KLF1 gene expression with response to thalidomide in β-thalassemia patients.
Patients will be grouped into thalidomide and non-thalidomide groups on the basis of their willingness to receive thalidomide therapy. Thalidomide will be given at an average dose of 1.5mg/kg/day (range 1-2mg/kg/day). Patients will be followed up for 12 months and data will be collected at different visits. After 12 months of thalidomide therapy patients will be divided into responders and non-responders for comparative analyses on the basis of increase in hemoglobin level.
Read the detailed description
Thalassemias are a group of genetic disorder of hemoglobin synthesis characterized by a decreased synthesis of globin chain. Thalassemias are classified as α-,β-, γ-,or δ-thalassemias depending upon the chain whose synthesis is reduced. Among these, β-thalassemia is more common. In β-thalassemia there is a decreased or absent hemoglobin A (HbA). Normal adult hemoglobin is primarily HbA, which represents approximately 98% of circulating hemoglobin. HbA is formed from 2 α and 2 β chains (α2β2). Combination of 2 α and 2 δ (α2δ2) form hemoglobin A2 (HbA2). Combination of 2 α and 2 γ (α2γ2) form hemoglobin F (HbF) which is a major form of hemoglobin in fetal life but comprises less than 1% of adult hemoglobin. Human beta-globin protein is encoded by HBB gene on chromosome 11, which contributes two β polypeptide chains. Therefore, one chain is inherited from the mother and one inherited from the father. In normal (homozygote) both genes are normal and produce normal β polypeptide chains to normal quantity. In heterozygote one gene is normal and other is abnormal which does not produce β polypeptide chain. Such condition is called β-thalassemia minor. In such a person normal gene produces enough β chain to maintain hemoglobin level. In abnormal homozygote both beta chain genes are abnormal and do not produce β polypeptide chain. Such condition is called β-thalassemia major. Reduced or absent production of β-globin chains with relative excess of α-chains cause imbalance and free α chains precipitate within the red blood cells. This result in extensive premature destruction of red cell precursors in the bone marrow, referred to as "ineffective erythropoiesis". The imbalance causes peripheral hemolysis as well. The two phenomena culminate in clinically significant anemia.
Severity of anemia due to β-thalassemia depends upon the type of mutations in β-globin gene. Mostly point mutations and frame shift mutations, in intronic as well exonic region, are reported in Pakistani β-thalassemia patients. Some mutations completely block the β-gene and thus no β globin chain is produced (βo) while in other mutations there is production of some β globin chains (β+). In β-thalassemia major both β globin alleles undergo mutations (βo/βo) and disease is severe. In β-thalassemia minor only one of β globin alleles are mutated (β+/β or βo/β) and patient is asymptomatic. β-thalassemia intermedia (β+/β+ or βo/β+) is the form of disease which is milder than thalassemia major but more severe than thalassemia minor. Besides less severe β+ mutations, inheritance of HbF inducing genetic variations and co-inheritance of alpha globin mutations can also ameliorate the clinical severity of the disease. In regards to HbF induction, genetic association studies have shown that there are at least three major loci that play a major role in increasing HbF and are associated with severity of β-thalassemia. These include -158 C > T in the promoter gene Gamma 2 (locus XmnI), intergenic regions HBS1L-MYB in the 6q23.3 chromosomal region, and the BCL11A gene on chromosome 2p16.1.
Annually about 60000 babies are born with thalassemia all over the world. Global annual incidence of β-thalassemia is estimated at a rate of 1/100,000 . Carrier rate for β-thalassemia in Pakistan ranges between 5-8%, and around 5000 children are diagnosed each year with the disease .
Severe anemia in β-thalassemia patients necessitates frequent transfusions, which lead to iron overload. Chronic anemia and iron overload lead to several complications including skeletal deformities, splenomegaly, osteoporosis, endocrinopathies, growth retardation and cardiac complications. Iron overload is treated with iron chelating agents. Definitive treatment is bone marrow transplantation (9).Thalassemia patients who do not respond well to blood transfusions can take hydroxyurea or thalidomide, and sometimes a combination of both.
Thalidomide, an immuno-modulatory drug is currently approved by FDA for the treatment of multiple myeloma and Leprosy. Thalidomide is used off-label for the treatment of β-thalassemia patients worldwide. Thalidomide has been reported to reduce or even eliminate the need for red blood cell transfusions in patients with transfusion dependent β-thalassemia . Although association of β globin gene mutations and genetic modifiers with severity of β-thalassemia have been well studied but association of these genetic factors with response to thalidomide therapy still needs to be explored. A study conducted on 48 Chinese patients showed association of Xmn1 HBG2, BCL11A \& HBSIL-MYB single nucleotide polymorphisms (SNPs) with response to thalidomide therapy. .
Improved terminal erythroid maturation and red blood cells stability are considered effective therapeutic approaches in the treatment of thalassemia. GATA1 and KLF1 are important transcription factor in erythroid differentiation which play critical role in regulation of globin gene expression. Studies reveal that increased expression of GATA1 and KLF1 causes induction of fetal hemoglobin (HbF) leading to reduced accumulation of α-globin chains in erythroid precursors and betterment of imbalance between α and β chains thus diminished ineffective erythropoiesis.
The current study aims to determine the in-vivo effects of thalidomide on GATA1 \& KLF1 gene expression in transfusion dependent β-thalassemia patients. Findings of the study will provide scientific evidence in support or against the off- label use of thalidomide in β-thalassemia patients. Results of the study regarding association of β-globin mutations and Xmn1 HBG2 BCL11A \& HBSIL-MYB single nucleotide polymorphisms with response to thalidomide therapy will explain variation in inter-individual response to the drug and thus help in predicting response before starting thalidomide therapy.
- Conditions
- Transfusion-dependent Beta-Thalassemia
- Being tested
- Thalidomide
- Keywords
- β-thalassemia, Thalidomide, β- globin mutations, Single Nucleotide Polymorphisms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThalidomideDrug
Also called Bludomide
Thalidomide given at an average dose of 1.5mg/kg/day
| Study group | Role | What they receive |
|---|---|---|
| Thalidomide Group | Experimental | In addition to routine β-thalassemia treatment patients in this group also received thalidomide at an average dose of 1.5mg/kg/day Receives: Drug: Thalidomide |
| Non-Thalidomide Group | No intervention | Participants received routine treatment for β-thalassemia such as regular blood transfusion and hydroxyurea at an average dose of 20mg/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response to thalidomide on the basis of increase in hemoglobin (Hb) level at 12 months of treatment.
On the basis of increase in Hb level patients categorized as follows:
- Excellent Responders (ER): In whom the Hb level raised to ≥9.0g/dl without any transfusion in the last two months.
- Good Responders (GR): In whom the Hb level raised to 7.0-8.9 g/dL without any transfusion in the last two months.
- Partial Responders (PR): In whom the Hb level remained <7.0 g/dL but did raise to a significantly higher level than the base-line without any transfusion in the last two months.
- Non-Responders (NR): In whom the Hb level did not show any significant improvement in comparison to the base-line
Measured: Baseline, 1 month, 6 months and 12 months
Association of different β- globin mutations with response to thalidomide
Amplification refractory mutation system polymerase chain reaction (ARMS-PCR) is used for detection of β- globin mutations.
Measured: Baseline
Association of Single Nucleotide Polymorphisms (SNPS) of HBG2, BCL11A and HBS1L-MYB with response to thalidomide
PCR \& DNA Sequencing are used for SNP genotyping
Measured: Baseline
Secondary outcomes (1)
Change from baseline in GATA1 and KLF1 gene expression at 12 months of thalidomide treatment
Real Time-Polymerase Chain Reaction (RT-PCR) is used for analysis of gene expression
Measured: Baseline and after 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2023
- Study start25 Jan 2022
- Primary completion20 Jul 2023
- Study completion31 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Transfusion-dependent Beta-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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Patients will be grouped into thalidomide and non-thalidomide groups on the basis of their willingness to receive thalidomide therapy. Thalidomide will be given at an average dose of 1.5mg/kg/day (range 1-2mg/kg/day). Patients will be followed up for 12 months and data will be collected at different visits.
- Masking
- None (open label)
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Blood Care Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Khyber Medical University Peshawar
- Responsible party
- Principal investigator, Inayat ur Rahman, Blood Care Clinic
- Investigators
- Sami Siraj, PhD, Study director, Institute Of Pharmaceutical Sciences, Khyber Medical University Peshawar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06146478
- Sponsor's protocol ID
- Dir/KMU-EB/TC/000863
- Status last verified
- Nov 2023
- First submitted
- 19 Nov 2023
- Last updated
- 24 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Ren Q, Zhou YL, Wang L, Chen YS, Ma YN, Li PP, Yin XL. Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia. Ann Hematol. 2018 Oct;97(10):1933-1939. doi: 10.1007/s00277-018-3395-5. Epub 2018 Jun 22.
PubMed 29931453Aerbajinai W, Zhu J, Gao Z, Chin K, Rodgers GP. Thalidomide induces gamma-globin gene expression through increased reactive oxygen species-mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis. Blood. 2007 Oct 15;110(8):2864-71. doi: 10.1182/blood-2007-01-065201. Epub 2007 Jul 9.
PubMed 17620452Yang K, Wu Y, Ma Y, Xiao J, Zhou Y, Yin X. The association of HBG2, BCL11A, and HBS1L-MYB polymorphisms to thalidomide response in Chinese beta-thalassemia patients. Blood Cells Mol Dis. 2020 Sep;84:102442. doi: 10.1016/j.bcmd.2020.102442. Epub 2020 Apr 26.
PubMed 32387854Ehnert S, Linnemann C, Braun B, Botsch J, Leibiger K, Hemmann P, Nussler AAK. One-Step ARMS-PCR for the Detection of SNPs-Using the Example of the PADI4 Gene. Methods Protoc. 2019 Jul 25;2(3):63. doi: 10.3390/mps2030063.
PubMed 31349745Grzasko N, Chocholska S, Goracy A, Hus M, Dmoszynska A. Thalidomide can promote erythropoiesis by induction of STAT5 and repression of external pathway of apoptosis resulting in increased expression of GATA-1 transcription factor. Pharmacol Rep. 2015 Dec;67(6):1193-200. doi: 10.1016/j.pharep.2015.05.011. Epub 2015 May 29.
PubMed 26481541Martinez PA, Li R, Ramanathan HN, Bhasin M, Pearsall RS, Kumar R, Suragani RNVS. Smad2/3-pathway ligand trap luspatercept enhances erythroid differentiation in murine beta-thalassaemia by increasing GATA-1 availability. J Cell Mol Med. 2020 Jun;24(11):6162-6177. doi: 10.1111/jcmm.15243. Epub 2020 Apr 29.
PubMed 32351032Jalali Far MA, Dehghani Fard A, Hajizamani S, Mossahebi-Mohammadi M, Yaghooti H, Saki N. Thalidomide is more efficient than sodium butyrate in enhancing GATA-1 and EKLF gene expression in erythroid progenitors derived from HSCs with beta-globin gene mutation. Int J Hematol Oncol Stem Cell Res. 2016 Jan 1;10(1):37-41.
PubMed 27047649Guillem F, Dussiot M, Colin E, Suriyun T, Arlet JB, Goudin N, Marcion G, Seigneuric R, Causse S, Gonin P, Gastou M, Deloger M, Rossignol J, Lamarque M, Choucair ZB, Gautier EF, Ducamp S, Vandekerckhove J, Moura IC, Maciel TT, Garrido C, An X, Mayeux P, Mohandas N, Courtois G, Hermine O. XPO1 regulates erythroid differentiation and is a new target for the treatment of beta-thalassemia. Haematologica. 2020 Sep 1;105(9):2240-2249. doi: 10.3324/haematol.2018.210054.
PubMed 33054049Yang K, Wu Y, Zhou Y, Long B, Lu Q, Zhou T, Wang L, Geng Z, Yin X. Thalidomide for Patients with beta-Thalassemia: A Multicenter Experience. Mediterr J Hematol Infect Dis. 2020 May 1;12(1):e2020021. doi: 10.4084/MJHID.2020.021. eCollection 2020.
PubMed 32395210Rahman IU, Khan MTM, Ali Z, Ahmad S, Shahid M, Zafar S, Aamir FF, Khan I, Ali M, Jelani M, Khan K, Ahmad N, Yousafzai Y, Mian AA, Siraj S. Thalidomide confers therapeutic benefit in beta thalassemia patients by enhancing hemoglobin and hematopoietic gene expression: A non-randomized clinical trial. Blood Cells Mol Dis. 2025 Jul-Sep;113-114:102936. doi: 10.1016/j.bcmd.2025.102936. Epub 2025 May 23.
PubMed 40446669
Study at a glance
From the registry record, last updated by the sponsor on 24 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deciphering Effects of Thalidomide on Red Blood Cells in Transfusion Dependents Beta Thalassemia Patients: A Pharmacodynamics and Pharmacogenetics Analysis
- ClinicalTrials.gov ID
- NCT06146478
- Acronym / sponsor ID
- Dir/KMU-EB/TC/000863
- Conditions
- Transfusion-dependent Beta-Thalassemia
- Keywords
- β-thalassemia, Thalidomide, β- globin mutations, Single Nucleotide Polymorphisms
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Blood Care ClinicUniversity, hospital or other
- Collaborators
- Khyber Medical University Peshawar
- Study start
- 25 Jan 2022 (actual)
- Primary completion
- 20 Jul 2023 (actual)
- Study completion
- 31 Oct 2023 (actual)
- First posted
- 24 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this Non-Randomized Clinical Trial is to determine the effects of thalidomide on red blood cells in transfusion dependent beta thalassemia patients. The main aims of this study are:
- To determine the therapeutic effect of Thalidomide on hemoglobin.
- To analyze association of different β- globin mutations with response to thalidomide in β-thalassemia patients.
- To analyze association of Single Nucleotide Polymorphisms (SNPS) of HBG2, BCL11A and HBS1L-MYB with response to thalidomide in β-thalassemia patients.
- To correlate GATA1 and KLF1 gene expression with response to thalidomide in β-thalassemia patients.
Patients will be grouped into thalidomide and non-thalidomide groups on the basis of their willingness to receive thalidomide therapy. Thalidomide will be given at an average dose of 1.5mg/kg/day (range 1-2mg/kg/day). Patients will be followed up for 12 months and data will be collected at different visits. After 12 months of thalidomide therapy patients will be divided into responders and non-responders for comparative analyses on the basis of increase in hemoglobin level.
Detailed description
Thalassemias are a group of genetic disorder of hemoglobin synthesis characterized by a decreased synthesis of globin chain. Thalassemias are classified as α-,β-, γ-,or δ-thalassemias depending upon the chain whose synthesis is reduced. Among these, β-thalassemia is more common. In β-thalassemia there is a decreased or absent hemoglobin A (HbA). Normal adult hemoglobin is primarily HbA, which represents approximately 98% of circulating hemoglobin. HbA is formed from 2 α and 2 β chains (α2β2). Combination of 2 α and 2 δ (α2δ2) form hemoglobin A2 (HbA2). Combination of 2 α and 2 γ (α2γ2) form hemoglobin F (HbF) which is a major form of hemoglobin in fetal life but comprises less than 1% of adult hemoglobin. Human beta-globin protein is encoded by HBB gene on chromosome 11, which contributes two β polypeptide chains. Therefore, one chain is inherited from the mother and one inherited from the father. In normal (homozygote) both genes are normal and produce normal β polypeptide chains to normal quantity. In heterozygote one gene is normal and other is abnormal which does not produce β polypeptide chain. Such condition is called β-thalassemia minor. In such a person normal gene produces enough β chain to maintain hemoglobin level. In abnormal homozygote both beta chain genes are abnormal and do not produce β polypeptide chain. Such condition is called β-thalassemia major. Reduced or absent production of β-globin chains with relative excess of α-chains cause imbalance and free α chains precipitate within the red blood cells. This result in extensive premature destruction of red cell precursors in the bone marrow, referred to as "ineffective erythropoiesis". The imbalance causes peripheral hemolysis as well. The two phenomena culminate in clinically significant anemia.
Severity of anemia due to β-thalassemia depends upon the type of mutations in β-globin gene. Mostly point mutations and frame shift mutations, in intronic as well exonic region, are reported in Pakistani β-thalassemia patients. Some mutations completely block the β-gene and thus no β globin chain is produced (βo) while in other mutations there is production of some β globin chains (β+). In β-thalassemia major both β globin alleles undergo mutations (βo/βo) and disease is severe. In β-thalassemia minor only one of β globin alleles are mutated (β+/β or βo/β) and patient is asymptomatic. β-thalassemia intermedia (β+/β+ or βo/β+) is the form of disease which is milder than thalassemia major but more severe than thalassemia minor. Besides less severe β+ mutations, inheritance of HbF inducing genetic variations and co-inheritance of alpha globin mutations can also ameliorate the clinical severity of the disease. In regards to HbF induction, genetic association studies have shown that there are at least three major loci that play a major role in increasing HbF and are associated with severity of β-thalassemia. These include -158 C > T in the promoter gene Gamma 2 (locus XmnI), intergenic regions HBS1L-MYB in the 6q23.3 chromosomal region, and the BCL11A gene on chromosome 2p16.1.
Annually about 60000 babies are born with thalassemia all over the world. Global annual incidence of β-thalassemia is estimated at a rate of 1/100,000 . Carrier rate for β-thalassemia in Pakistan ranges between 5-8%, and around 5000 children are diagnosed each year with the disease .
Severe anemia in β-thalassemia patients necessitates frequent transfusions, which lead to iron overload. Chronic anemia and iron overload lead to several complications including skeletal deformities, splenomegaly, osteoporosis, endocrinopathies, growth retardation and cardiac complications. Iron overload is treated with iron chelating agents. Definitive treatment is bone marrow transplantation (9).Thalassemia patients who do not respond well to blood transfusions can take hydroxyurea or thalidomide, and sometimes a combination of both.
Thalidomide, an immuno-modulatory drug is currently approved by FDA for the treatment of multiple myeloma and Leprosy. Thalidomide is used off-label for the treatment of β-thalassemia patients worldwide. Thalidomide has been reported to reduce or even eliminate the need for red blood cell transfusions in patients with transfusion dependent β-thalassemia . Although association of β globin gene mutations and genetic modifiers with severity of β-thalassemia have been well studied but association of these genetic factors with response to thalidomide therapy still needs to be explored. A study conducted on 48 Chinese patients showed association of Xmn1 HBG2, BCL11A \& HBSIL-MYB single nucleotide polymorphisms (SNPs) with response to thalidomide therapy. .
Improved terminal erythroid maturation and red blood cells stability are considered effective therapeutic approaches in the treatment of thalassemia. GATA1 and KLF1 are important transcription factor in erythroid differentiation which play critical role in regulation of globin gene expression. Studies reveal that increased expression of GATA1 and KLF1 causes induction of fetal hemoglobin (HbF) leading to reduced accumulation of α-globin chains in erythroid precursors and betterment of imbalance between α and β chains thus diminished ineffective erythropoiesis.
The current study aims to determine the in-vivo effects of thalidomide on GATA1 \& KLF1 gene expression in transfusion dependent β-thalassemia patients. Findings of the study will provide scientific evidence in support or against the off- label use of thalidomide in β-thalassemia patients. Results of the study regarding association of β-globin mutations and Xmn1 HBG2 BCL11A \& HBSIL-MYB single nucleotide polymorphisms with response to thalidomide therapy will explain variation in inter-individual response to the drug and thus help in predicting response before starting thalidomide therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Patients will be grouped into thalidomide and non-thalidomide groups on the basis of their willingness to receive thalidomide therapy. Thalidomide will be given at an average dose of 1.5mg/kg/day (range 1-2mg/kg/day). Patients will be followed up for 12 months and data will be collected at different visits.
| Arm | Type | Receives |
|---|---|---|
| Thalidomide Group | Experimental | Drug: ThalidomideIn addition to routine β-thalassemia treatment patients in this group also received thalidomide at an average dose of 1.5mg/kg/day |
| Non-Thalidomide Group | No intervention | –Participants received routine treatment for β-thalassemia such as regular blood transfusion and hydroxyurea at an average dose of 20mg/kg/day |
Who may qualify
- Ages
- 1 year to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- Diagnosed transfusion dependent β-thalassemia patients
- Possess a verified pre transfusion Hb electrophoresis report performed at age≥ 6 months
Key exclusion criteria (2 listed)
- Patients with active metabolic or systemic comorbidities
- Patients with autologous antibodies, AIHA or hypersplenism
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 |
|---|---|---|
| ThalidomideAlso: BludomideThalidomide given at an average dose of 1.5mg/kg/day | Drug | Thalidomide Group |
Primary outcome
Response to thalidomide on the basis of increase in hemoglobin (Hb) level at 12 months of treatment.
Time frame: Baseline, 1 month, 6 months and 12 months
On the basis of increase in Hb level patients categorized as follows: 1. Excellent Responders (ER): In whom the Hb level raised to ≥9.0g/dl without any transfusion in the last two months. 2. Good Responders (GR): In whom the Hb level raised to 7.0-8.9 g/dL without any transfusion in the last two months. 3. Partial Responders (PR): In whom the Hb level remained <7.0 g/dL but did raise to a significantly higher level than the base-line without any transfusion in the last two months. 4. Non-Responders (NR): In whom the Hb level did not show any significant improvement in comparison to the base-line
Association of different β- globin mutations with response to thalidomide
Time frame: Baseline
Amplification refractory mutation system polymerase chain reaction (ARMS-PCR) is used for detection of β- globin mutations.
Association of Single Nucleotide Polymorphisms (SNPS) of HBG2, BCL11A and HBS1L-MYB with response to thalidomide
Time frame: Baseline
PCR \& DNA Sequencing are used for SNP genotyping
1 secondary outcome
Change from baseline in GATA1 and KLF1 gene expression at 12 months of thalidomide treatment
Time frame: Baseline and after 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Nov 2023.
- Background: PubMed 29931453Ren Q, Zhou YL, Wang L, Chen YS, Ma YN, Li PP, Yin XL. Clinical trial on the effects of thalidomide on hemoglobin synthesis in patients with moderate thalassemia intermedia. Ann Hematol. 2018 Oct;97(10):1933-1939. doi: 10.1007/s00277-018-3395-5. Epub 2018 Jun 22.
- Background: PubMed 17620452Aerbajinai W, Zhu J, Gao Z, Chin K, Rodgers GP. Thalidomide induces gamma-globin gene expression through increased reactive oxygen species-mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis. Blood. 2007 Oct 15;110(8):2864-71. doi: 10.1182/blood-2007-01-065201. Epub 2007 Jul 9.
- Background: PubMed 32387854Yang K, Wu Y, Ma Y, Xiao J, Zhou Y, Yin X. The association of HBG2, BCL11A, and HBS1L-MYB polymorphisms to thalidomide response in Chinese beta-thalassemia patients. Blood Cells Mol Dis. 2020 Sep;84:102442. doi: 10.1016/j.bcmd.2020.102442. Epub 2020 Apr 26.
- Background: PubMed 31349745Ehnert S, Linnemann C, Braun B, Botsch J, Leibiger K, Hemmann P, Nussler AAK. One-Step ARMS-PCR for the Detection of SNPs-Using the Example of the PADI4 Gene. Methods Protoc. 2019 Jul 25;2(3):63. doi: 10.3390/mps2030063.
- Background: PubMed 26481541Grzasko N, Chocholska S, Goracy A, Hus M, Dmoszynska A. Thalidomide can promote erythropoiesis by induction of STAT5 and repression of external pathway of apoptosis resulting in increased expression of GATA-1 transcription factor. Pharmacol Rep. 2015 Dec;67(6):1193-200. doi: 10.1016/j.pharep.2015.05.011. Epub 2015 May 29.
- Background: PubMed 32351032Martinez PA, Li R, Ramanathan HN, Bhasin M, Pearsall RS, Kumar R, Suragani RNVS. Smad2/3-pathway ligand trap luspatercept enhances erythroid differentiation in murine beta-thalassaemia by increasing GATA-1 availability. J Cell Mol Med. 2020 Jun;24(11):6162-6177. doi: 10.1111/jcmm.15243. Epub 2020 Apr 29.
- Background: PubMed 27047649Jalali Far MA, Dehghani Fard A, Hajizamani S, Mossahebi-Mohammadi M, Yaghooti H, Saki N. Thalidomide is more efficient than sodium butyrate in enhancing GATA-1 and EKLF gene expression in erythroid progenitors derived from HSCs with beta-globin gene mutation. Int J Hematol Oncol Stem Cell Res. 2016 Jan 1;10(1):37-41.
- Background: PubMed 33054049Guillem F, Dussiot M, Colin E, Suriyun T, Arlet JB, Goudin N, Marcion G, Seigneuric R, Causse S, Gonin P, Gastou M, Deloger M, Rossignol J, Lamarque M, Choucair ZB, Gautier EF, Ducamp S, Vandekerckhove J, Moura IC, Maciel TT, Garrido C, An X, Mayeux P, Mohandas N, Courtois G, Hermine O. XPO1 regulates erythroid differentiation and is a new target for the treatment of beta-thalassemia. Haematologica. 2020 Sep 1;105(9):2240-2249. doi: 10.3324/haematol.2018.210054.
- Background: PubMed 32395210Yang K, Wu Y, Zhou Y, Long B, Lu Q, Zhou T, Wang L, Geng Z, Yin X. Thalidomide for Patients with beta-Thalassemia: A Multicenter Experience. Mediterr J Hematol Infect Dis. 2020 May 1;12(1):e2020021. doi: 10.4084/MJHID.2020.021. eCollection 2020.
- Derived from this study: PubMed 40446669Rahman IU, Khan MTM, Ali Z, Ahmad S, Shahid M, Zafar S, Aamir FF, Khan I, Ali M, Jelani M, Khan K, Ahmad N, Yousafzai Y, Mian AA, Siraj S. Thalidomide confers therapeutic benefit in beta thalassemia patients by enhancing hemoglobin and hematopoietic gene expression: A non-randomized clinical trial. Blood Cells Mol Dis. 2025 Jul-Sep;113-114:102936. doi: 10.1016/j.bcmd.2025.102936. Epub 2025 May 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.
Sami Siraj, PhD study director
Institute Of Pharmaceutical Sciences, Khyber Medical University Peshawar
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Thalidomide in people with Transfusion-dependent Beta-Thalassemia, run by Blood Care Clinic at 1 site in Pakistan.
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 2 inclusion and 2 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 24 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Response to thalidomide on the basis of increase in hemoglobin (Hb) level at 12 months of treatment. (time frame: Baseline, 1 month, 6 months and 12 months). The study lists 3 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 NCT06146478, which also lists 10 linked publications.
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 24 Nov 2023.