Safety and Efficacy of Hemoglobin F Inducers in Patients With Beta Thalassemia
Safety and Efficacy of Hemoglobin F Inducers in Patients With Beta Thalassemia: a Prospective 12 Months Study
The aim of this study is to determine the safety and therapeutic effect of HbF inducers (combination therapy: thalidomide and hydroxyurea) on beta thalassemia patients. The main objectives of this study are:
- To determine the therapeutic efficacy of HbF inducers (combination therapy: thalidomide and hydroxyurea) on hemoglobin level and blood transfusion in beta thalassemia patients.
- To determine the safety of HbF inducers (combination therapy: thalidomide and hydroxyurea) in beta thalassemia patients
- To determine effect of HbF inducers (combination therapy: thalidomide and hydroxyurea) on quality of life of beta thalassemia patients
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
This is a two-arm comparative study. One group is the interventional group, in which all patients will receive thalidomide and hydroxyurea. Low-dose Thalidomide will be administered to patients at a low dose of 0.5 to 4 mg/kg orally every day for 12 months until continuous transfusion-dependency or unacceptable toxicity occurs. The starting dose of hydroxyurea will be 10-20 mg/kg per day. The second group will be the control group for blood transfusion.
In the intervention group, 114 confirmed diagnoses of beta thalassemia ascertained by Hemoglobin Electrophoresis or HPLC report performed pre-transfusion or genetic testing profile (comprising PCR or HBB gene sequencing) suggestive of β-thalassemia syndrome will be included. To assess the therapeutic efficacy of HbF inducers (combination therapy: thalidomide and hydroxyurea), the number of blood transfusions and hemoglobin level will be assessed as per the given schedule.
. Adverse events will be recorded at each follow-up to assess the safety of the therapy. The patient/guardian/parent will be specifically asked about paresthesia, rash, constipation, unexplained infections, bleeding symptoms, headache, syncope, focal weakness, and behavioral changes. All participants will be asked to report any adverse reactions and will be questioned about adverse events during the study visit. EORTC QLQ C-30 URDU version, a self-administered questionnaire, will be filled by each participant at baseline and 6 months.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Fariha Sardar, MBBS, FCPS
- Número de telefone: +923335517877
- E-mail: doc.fariha@yahoo.com
Estude backup de contato
- Nome: Fariha Sardar, MBBS, FCPS
- Número de telefone: +923350941494
- E-mail: afzaal2kmt20@gamil.com
Locais de estudo
-
-
Punjab Province
-
Rawalpindi, Punjab Province, Paquistão
- Recrutamento
- Riphah International University
-
Contato:
- Fariha Sadar, MBBS, FCPS
- Número de telefone: +923335517877
- E-mail: doc.fariha@yahoo.com
-
Contato:
- Fariha Saradr, MBBS, FCPS
- Número de telefone: +923350941494
- E-mail: afzaal2kmt20@gamil.com
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
- Filho
- Adulto
- Adulto mais velho
Aceita Voluntários Saudáveis
Descrição
Inclusion criteria:
- Confirmed diagnosis of Beta thalassemia Major (BTM) ascertained by Hemoglobin Electrophoresis or HPLC report performed pre-transfusion or genetic testing profile (comprising PCR or HBB gene sequencing) suggestive of β-thalassemia syndrome.
- All ages and both genders will be included
- Written informed consent
Exclusion criteria:
- Pregnancy or unwilling to follow contraception or planning conception (Enrolled female patients will be strictly advised to avoid pregnancy during the study period and until 6 months after thalidomide withdrawal.
- Hemoglobinopathies other than beta thalassemia
- History of neurological problems
- Inability to regularly follow up
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Não randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Nenhum (rótulo aberto)
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Sem intervenção: Blood transfusion Group
Control group will be on regular blood transfusion and iron chelation therapy
|
|
|
Experimental: HbF inducers
All patients will receive thalidomide and hydroxyurea.
Low dose Thalidomide will be administered to patients at a low dose of 0.5 to 4 mg/kg orally every day for 12 months until continuous transfusion-dependency or unacceptable toxicity occurred.
The starting dose of hydroxyurea will be 10-20 mg/kg per day.
|
Tab Thalidomide 0.5 to 4 mg/kg orally every day for 12 months
Outros nomes:
Tab Hydroxyurea 10-20 mg/kg per day for 12 months
Outros nomes:
|
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Improvement in the hemoglobin level
Prazo: 6 months
|
To evaluate the Improvement in Hemoglobin level, response criteria are defined as follows: Major response, an elevation in total Hb level of ≥2 g/dL Minor response, an elevation in total Hb level of 1 to 2 g/dL, or Hb not substantially increased (<1 g/dL) but the patients achieve Hb>7 g/L No response, an elevation in total Hb level of <1 g/dL |
6 months
|
|
Decrease in transfusion requirement
Prazo: 6 months
|
To evaluate the decrease in transfusion requirement, response criteria are defined as follows: Major response: reduce transfusion requirements by ≥25% after 6 months of therapy compared to baseline. Minor response: reduce transfusion requirement by <25 % after 6 months of therapy, No response: same blood transfusion requirement as baseline |
6 months
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Serum Bilirubin levels
Prazo: 1 year
|
0.2- 1.1 mg/dL Normal >1.1- 3 mg/dL Mild derangement >3 mg/dL Severe derangement
|
1 year
|
|
Change in ALT levels
Prazo: 1 year
|
ALT levels range: 0- 42 U/L Normal >42-126 U/L Mild severity >126- 420 U/L Moderate severity >420 U/L severe |
1 year
|
|
Change in serum creatinine levels
Prazo: 1 year
|
Serum creatinine 0.2 - 1.1 mg/dL Normal >1.1- 1.5 mg/dL Mild severity >1.5- 3.0 mg/dL Moderate severity >3 mg/dL Severe
|
1 year
|
|
Assess Quality of life by using EORTC QLQ-C30
Prazo: 6 months
|
EORTC QLQ C-30 URDU version, a self-administered questionnaire, will be filled by each participant at baseline and 6 months. Functional/Global: 100 = perfect function. 0 = no function. 10-point change = clinically meaningful. Symptoms: 0 = no symptoms. 100 = maximum symptoms 10-point increase = worse symptom burden. |
6 months
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Fariha Sardar, MBBS, FCPS, Riphah International University, Rwp
Publicações e links úteis
Publicações Gerais
- 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.
- 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.
- Ali Z, Ismail M, Rehman IU, Rani GF, Ali M, Khan MTM. Long-term clinical efficacy and safety of thalidomide in patients with transfusion-dependent beta-thalassemia: results from Thal-Thalido study. Sci Rep. 2023 Aug 21;13(1):13592. doi: 10.1038/s41598-023-40849-4.
- Tuo Y, Li Y, Li Y, Ma J, Yang X, Wu S, Jin J, He Z. Global, regional, and national burden of thalassemia, 1990-2021: a systematic analysis for the global burden of disease study 2021. EClinicalMedicine. 2024 May 6;72:102619. doi: 10.1016/j.eclinm.2024.102619. eCollection 2024 Jun.
- Shah S, Sheth R, Shah K, Patel K. Safety and effectiveness of thalidomide and hydroxyurea combination in beta-thalassaemia intermedia and major: a retrospective pilot study. Br J Haematol. 2020 Feb;188(3):e18-e21. doi: 10.1111/bjh.16272. Epub 2019 Nov 11. No abstract available.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Termos MeSH relevantes adicionais
- Doenças Genéticas, Congênitas
- Doenças Hematológicas
- Anemia Hemolítica Congênita
- Anemia Hemolítica
- Anemia
- Hemoglobinopatias
- Doenças e Anormalidades Congênitas, Hereditárias e Neonatais
- Doenças hemic e linfáticas
- Talassemia
- Produtos químicos orgânicos
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Compostos heterocíclicos, 2 anel
- Compostos heterocíclicos, anel fundido
- Ácidos carboxílicos
- Amidas
- Piperidinas
- Ftalimidas
- Ácidos ftaléticos
- Ácidos, carbocíclicos
- Piperidones
- Isoindoles
- Uréia
- Talidomida
- Hidroxiureia
Outros números de identificação do estudo
- Riphah/IIMC/IRB/26/1048
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .