Efficacy of Combination of Hdroxyurea and Thalidomide Over Hydroxyurea or Thalidomide in the Treatment of Transfusion Dependent Thalassemia in Children

Summary

The goal of this clinical trial is to find out the efficacy of combined Hydroxyurea and thalidomide transfusion dependent thalassemia patients. The main objectives are to compare the level of Hb, Transfusion interval, serum ferritin level before \& after treatment between single and combination of thalidomide and HU. Researcher will compare the effectiveness of combined hydroxyurea and thalidomide and hydroxyurea and thalidomide alone. Participants will be divided in three groups: Group I: will take combination of HU and Thalidomide. Group II: Will take HU alone and Group III: Will take Thalidomide alone and outcome will be recorded.

Timeline

Start

2023-11-01

Primary completion

2026-01-30

Completion

2026-01-30

Publications

• 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.
• Background 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.
• Background 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.
• Background 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.
• Background 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.
• Background Costa E, Cappellini MD, Rivella S, Chilin A, Alessi E, Riccaboni M, Leufkens HGM, Luzzatto L. Emergent treatments for beta-thalassemia and orphan drug legislations. Drug Discov Today. 2022 Nov;27(11):103342. doi: 10.1016/j.drudis.2022.103342. Epub 2022 Sep 1.
• Background Fard AD, Hosseini SA, Shahjahani M, Salari F, Jaseb K. Evaluation of Novel Fetal Hemoglobin Inducer Drugs in Treatment of beta-Hemoglobinopathy Disorders. Int J Hematol Oncol Stem Cell Res. 2013;7(3):47-54.
• 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.
• 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.
• Background Green NS, Manwani D, Qureshi M, Ireland K, Sinha A, Smaldone AM. Decreased fetal hemoglobin over time among youth with sickle cell disease on hydroxyurea is associated with higher urgent hospital use. Pediatr Blood Cancer. 2016 Dec;63(12):2146-2153. doi: 10.1002/pbc.26161. Epub 2016 Aug 30.
• 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.
• Background 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.
• Background Li X, Hu S, Liu Y, Huang J, Hong W, Xu L, Xu H, Fang J. Efficacy of Thalidomide Treatment in Children With Transfusion Dependent beta-Thalassemia: A Retrospective Clinical Study. Front Pharmacol. 2021 Aug 12;12:722502. doi: 10.3389/fphar.2021.722502. eCollection 2021.
• Background Masera N, Tavecchia L, Capra M, Cazzaniga G, Vimercati C, Pozzi L, Biondi A, Masera G. Optimal response to thalidomide in a patient with thalassaemia major resistant to conventional therapy. Blood Transfus. 2010 Jan;8(1):63-5. doi: 10.2450/2009.0102-09. No abstract available.
• 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.
• Background Rigano P, Pecoraro A, Calzolari R, Troia A, Acuto S, Renda D, Pantalone GR, Maggio A, Di Marzo R. Desensitization to hydroxycarbamide following long-term treatment of thalassaemia intermedia as observed in vivo and in primary erythroid cultures from treated patients. Br J Haematol. 2010 Dec;151(5):509-15. doi: 10.1111/j.1365-2141.2010.08397.x. Epub 2010 Oct 19.
• 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.
• 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/
• Background Thompson AA, Walters MC, Kwiatkowski J, Rasko JEJ, Ribeil JA, Hongeng S, Magrin E, Schiller GJ, Payen E, Semeraro M, Moshous D, Lefrere F, Puy H, Bourget P, Magnani A, Caccavelli L, Diana JS, Suarez F, Monpoux F, Brousse V, Poirot C, Brouzes C, Meritet JF, Pondarre C, Beuzard Y, Chretien S, Lefebvre T, Teachey DT, Anurathapan U, Ho PJ, von Kalle C, Kletzel M, Vichinsky E, Soni S, Veres G, Negre O, Ross RW, Davidson D, Petrusich A, Sandler L, Asmal M, Hermine O, De Montalembert M, Hacein-Bey-Abina S, Blanche S, Leboulch P, Cavazzana M. Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia. N Engl J Med. 2018 Apr 19;378(16):1479-1493. doi: 10.1056/NEJMoa1705342.
• 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.
• 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.
• 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.

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