Deciphering Effects of Thalidomide on Red Blood Cells in Transfusion Dependents Beta Thalassemia Patients

NCT06146478 | Completed Phase 3

• 1 other identifier: Dir/KMU-EB/TC/000863
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief 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.
• 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.

Conditions

Transfusion-dependent Beta-Thalassemia

Keywords

β-thalassemia; Thalidomide; β- globin mutations; Single Nucleotide Polymorphisms

Outcome Measures

Primary Outcomes (3)

• 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: 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

  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.

  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

  Baseline

Secondary Outcomes (1)

• Change from baseline in GATA1 and KLF1 gene expression at 12 months of thalidomide treatment

  Baseline and after 12 months

Study Arms (2)

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

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

Interventions

Thalidomide DRUG

Thalidomide given at an average dose of 1.5mg/kg/day

Also known as: Bludomide

Thalidomide Group

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosed transfusion dependent β-thalassemia patients
• Possess a verified pre transfusion Hb electrophoresis report performed at age≥ 6 months

You may not qualify if:

• Patients with active metabolic or systemic comorbidities
• Patients with autologous antibodies, AIHA or hypersplenism

Sponsors & Collaborators

• Blood Care Clinic: lead
• Khyber Medical University Peshawar: collaborator

Study Sites (1)

Blood Care Clinic

Peshawar, Khyber Pakhtunkhwa, Pakistan

Location

Related Publications (10)

• 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.

  PMID: 29931453 BACKGROUND

• Aerbajinai 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.

  PMID: 17620452 BACKGROUND

• Yang 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.

  PMID: 32387854 BACKGROUND

• Ehnert 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.

  PMID: 31349745 BACKGROUND

• Grzasko 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.

  PMID: 26481541 BACKGROUND

• Martinez 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.

  PMID: 32351032 BACKGROUND

• Jalali 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.

  PMID: 27047649 BACKGROUND

• Guillem 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.

  PMID: 33054049 BACKGROUND

• Yang 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.

  PMID: 32395210 BACKGROUND

• Rahman 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.

  PMID: 40446669 DERIVED

MeSH Terms

Interventions

Thalidomide

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Sami Siraj, PhD

  Institute Of Pharmaceutical Sciences, Khyber Medical University Peshawar

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: No masking
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD Scholar

Model Details: 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.

Study Record Dates

• First Submitted: November 19, 2023
• First Posted: November 24, 2023
• Study Start: January 25, 2022
• Primary Completion: July 20, 2023
• Study Completion: October 31, 2023
• Last Updated: November 24, 2023

Record last verified: 2023-11

Locations

PA (1)