Safety & Efficacy of Thalidomide in Children With Transfusion Dependent Thalassemia

NCT06098014 | Completed Phase 1 DMC

• 1 other identifier: 4280
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Transfusion Dependent Thalassemia (TDT) is emerging as a global public health concern. Hemopoietic stem cell transplantation (HSCT) is the only curative treatment. But its adoption is limited due to lack of Human leukocyte antigen (HLA) matched donor, experienced centers and high initial cost. So, researches are going on in search of an effective, safe, easily available treatment option. Thalidomide a Fetal Hemoglobin (HbF) inducing drug shown to be effective in treatment of TDT patients in few case reports and small scale prospective and retrospective studies. However, most of these researches were done in adolescent and adult population. No randomized control trial was done to determine the safety and efficacy of Thalidomide in TDT children. So, this study will predict the safety and efficacy of Thalidomide in TDT children and will play an important role in planning a cost effective and affordable treatment option for TDT children. This single centered non blinded quasi randomized clinical trial will be conducted at the Department of Pediatric Hematology and Oncology in Bangabandhu Sheikh Mujib Medical University (BSMMU), Bangladesh for one year of period. The objective of this study is to assess the safety and efficacy of Thalidomide in TDT children 30 transfusion dependent thalassemia children of 3-18 years old will be included. This study will involve minimum physical risk to the patient. Written informed consent will be taken from parents or study subjects after brief explanation of the purpose and procedure. They will also be informed about the freedom to participate or not to participate at any time. Privacy and confidentiality will be safe guarded. History regarding age, sex, height, weight of these patients will be taken. Through physical examinations and laboratory investigations including complete blood count (CBC), Hb electrophoresis, serum Ferritin, serum creatinine, serum glutamic pyruvic transaminase (SGPT), serum lactate dehydrogenase (LDH) will be done. Data will be collected in a predesigned questionnaire and will be kept confidential. Statistical analysis will be done using the statistical package for social science (SPSS) software .

Conditions

Transfusion-dependent Thalassemia

Keywords

Thalidomide,; Thalassemia; Children

Outcome Measures

Primary Outcomes (1)

• change in Hb level

  gm/dl

  12 weeks after treatment initiation.

Secondary Outcomes (4)

• blood transfusion frequency

  3 months from initiation of treatment

• change in Hb F

  3 months after initiation of treatment

• Change in s. Ferritin level

  3 months after initiation of treatment

• Adverse effect

  3 months after initiation of treatment

Study Arms (2)

Thalidomide group

ACTIVE COMPARATOR

Thalidomide group

Drug: Thalidomide Capsules

Placebo group

PLACEBO COMPARATOR

Placebo group

Drug: Placebo

Interventions

Thalidomide Capsules DRUG

To see safety and efficacy of Thalidomide in Transfusion depended thalassemia

Thalidomide group

Placebo DRUG

compare with Thalidomide

Placebo group

Eligibility Criteria

• Age: 3 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients diagnosed as transfusion dependent thalassemia
• Age ranged from 3-18 years
• Blood transfusion for more than 1 year.

You may not qualify if:

• Active systemic illness,
• Abnormal liver and kidney functions;
• Severe cardiopulmonary or cerebrovascular diseases;
• Recent fracture or recent major surgery
• Use of drugs that might affect Hb levels 3 months before enrollment;
• Any bleeding disorder .

Sponsors & Collaborators

• Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh: lead

Study Sites (1)

Bangabandhu Sheikh Mujib Medical University

Dhaka, 1000, Bangladesh

Location

Related Publications (20)

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  PMID: 24505535 BACKGROUND

• Farmakis D, Porter J, Taher A, Domenica Cappellini M, Angastiniotis M, Eleftheriou A. 2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia. Hemasphere. 2022 Jul 29;6(8):e732. doi: 10.1097/HS9.0000000000000732. eCollection 2022 Aug.

  PMID: 35928543 BACKGROUND

• Fozza C, Pardini S, Giannico DB, Targhetta C, Di Tucci AA, Dessalvi P, Angelucci E, Dore F. Dramatic erythroid response to low-dose thalidomide in two patients with transfusion independent thalassemia and severe post-transfusional alloimmune hemolysis. Am J Hematol. 2015 Jul;90(7):E141. doi: 10.1002/ajh.24030. No abstract available.

  PMID: 25850682 BACKGROUND

• Hossain MS, Raheem E, Sultana TA, Ferdous S, Nahar N, Islam S, Arifuzzaman M, Razzaque MA, Alam R, Aziz S, Khatun H, Rahim A, Morshed M. Thalassemias in South Asia: clinical lessons learnt from Bangladesh. Orphanet J Rare Dis. 2017 May 18;12(1):93. doi: 10.1186/s13023-017-0643-z.

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• Jain M, Chakrabarti P, Dolai TK, Ghosh P, Mandal PK, Baul SN, De R. Comparison of efficacy and safety of thalidomide vs hydroxyurea in patients with Hb E-beta thalassemia - a pilot study from a tertiary care Centre of India. Blood Cells Mol Dis. 2021 May;88:102544. doi: 10.1016/j.bcmd.2021.102544. Epub 2021 Feb 3.

  PMID: 33610115 BACKGROUND

• Lu Y, Wei Z, Yang G, Lai Y, Liu R. Investigating the Efficacy and Safety of Thalidomide for Treating Patients With ss-Thalassemia: A Meta-Analysis. Front Pharmacol. 2022 Jan 11;12:814302. doi: 10.3389/fphar.2021.814302. eCollection 2021.

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  PMID: 20104280 BACKGROUND

• Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011 Sep 29;118(13):3479-88. doi: 10.1182/blood-2010-08-300335. Epub 2011 Aug 2.

  PMID: 21813448 BACKGROUND

• Shah FT, Sayani F, Trompeter S, Drasar E, Piga A. Challenges of blood transfusions in beta-thalassemia. Blood Rev. 2019 Sep;37:100588. doi: 10.1016/j.blre.2019.100588. Epub 2019 Jul 6.

  PMID: 31324412 BACKGROUND

• Taher A, Vichinsky E, Musallam K, Cappellini MD, Viprakasit V, authors. Weatherall D, editor. Guidelines for the Management of Non Transfusion Dependent Thalassaemia (NTDT) [Internet]. Nicosia (Cyprus): Thalassaemia International Federation; 2013. Available from http://www.ncbi.nlm.nih.gov/books/NBK190453/

  PMID: 24672826 BACKGROUND

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  PMID: 29669226 BACKGROUND

• Weatherall DJ. The Evolving Spectrum of the Epidemiology of Thalassemia. Hematol Oncol Clin North Am. 2018 Apr;32(2):165-175. doi: 10.1016/j.hoc.2017.11.008.

  PMID: 29458724 BACKGROUND

• Wolman IJ, Ortolani M. Some clinical features of Cooley's anemia patients as related to transfusion schedules. Ann N Y Acad Sci. 1969 Nov 20;165(1):407-14. doi: 10.1111/j.1749-6632.1969.tb27811.x. No abstract available.

  PMID: 5260163 BACKGROUND

• Yassin AK. Promising Response to Thalidomide in Symptomatic beta-Thalassemia. Indian J Hematol Blood Transfus. 2020 Apr;36(2):337-341. doi: 10.1007/s12288-019-01231-5. Epub 2019 Nov 18.

  PMID: 32425386 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 RESULT

• Aguilar-Lopez LB, Delgado-Lamas JL, Rubio-Jurado B, Perea FJ, Ibarra B. Thalidomide therapy in a patient with thalassemia major. Blood Cells Mol Dis. 2008 Jul-Aug;41(1):136-7. doi: 10.1016/j.bcmd.2008.03.001. Epub 2008 Apr 24. No abstract available.

  PMID: 18439858 RESULT

• Bou-Fakhredin R, De Franceschi L, Motta I, Cappellini MD, Taher AT. Pharmacological Induction of Fetal Hemoglobin in beta-Thalassemia and Sickle Cell Disease: An Updated Perspective. Pharmaceuticals (Basel). 2022 Jun 16;15(6):753. doi: 10.3390/ph15060753.

  PMID: 35745672 RESULT

• Cappellini MD, Porter JB, Viprakasit V, Taher AT. A paradigm shift on beta-thalassaemia treatment: How will we manage this old disease with new therapies? Blood Rev. 2018 Jul;32(4):300-311. doi: 10.1016/j.blre.2018.02.001. Epub 2018 Feb 12.

  PMID: 29455932 RESULT

• Chen JM, Zhu WJ, Liu J, Wang GZ, Chen XQ, Tan Y, Xu WW, Qu LW, Li JY, Yang HJ, Huang L, Cai N, Wang WD, Huang K, Xu JQ, Li GH, He S, Luo TY, Huang Y, Liu SH, Wu WQ, Lu QY, Zhou MG, Chen SY, Li RL, Hu ML, Huang Y, Wei JH, Li JM, Chen SJ, Zhou GB. Safety and efficacy of thalidomide in patients with transfusion-dependent beta-thalassemia: a randomized clinical trial. Signal Transduct Target Ther. 2021 Nov 18;6(1):405. doi: 10.1038/s41392-021-00811-0.

  PMID: 34795208 RESULT

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  PMID: 36058507 RESULT

MeSH Terms

Conditions

Thalassemia

Interventions

Thalidomide

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 12, 2023
• First Posted: October 24, 2023
• Study Start: March 1, 2023
• Primary Completion: February 28, 2024
• Study Completion: February 28, 2024
• Last Updated: April 9, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: January 2025

Locations

BA (1)