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
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
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 estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Fariha Sardar, MBBS, FCPS
- Número de teléfono: +923335517877
- Correo electrónico: doc.fariha@yahoo.com
Copia de seguridad de contactos de estudio
- Nombre: Fariha Sardar, MBBS, FCPS
- Número de teléfono: +923350941494
- Correo electrónico: afzaal2kmt20@gamil.com
Ubicaciones de estudio
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Punjab Province
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Rawalpindi, Punjab Province, Pakistán
- Reclutamiento
- Riphah International University
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Contacto:
- Fariha Sadar, MBBS, FCPS
- Número de teléfono: +923335517877
- Correo electrónico: doc.fariha@yahoo.com
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Contacto:
- Fariha Saradr, MBBS, FCPS
- Número de teléfono: +923350941494
- Correo electrónico: afzaal2kmt20@gamil.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Niño
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Sin intervención: Blood transfusion Group
Control group will be on regular blood transfusion and iron chelation therapy
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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.
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Tab Thalidomide 0.5 to 4 mg/kg orally every day for 12 months
Otros nombres:
Tab Hydroxyurea 10-20 mg/kg per day for 12 months
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Improvement in the hemoglobin level
Periodo de tiempo: 6 months
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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
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Decrease in transfusion requirement
Periodo de tiempo: 6 months
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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
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Serum Bilirubin levels
Periodo de tiempo: 1 year
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0.2- 1.1 mg/dL Normal >1.1- 3 mg/dL Mild derangement >3 mg/dL Severe derangement
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1 year
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Change in ALT levels
Periodo de tiempo: 1 year
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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
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Change in serum creatinine levels
Periodo de tiempo: 1 year
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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
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1 year
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Assess Quality of life by using EORTC QLQ-C30
Periodo de tiempo: 6 months
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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
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Fariha Sardar, MBBS, FCPS, Riphah International University, Rwp
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Enfermedades Genéticas Congénitas
- Enfermedades hematológicas
- Anemia Hemolítica Congénita
- Anemia Hemolítica
- Anemia
- Hemoglobinopatías
- Enfermedades y anomalías congénitas, hereditarias y neonatales
- Enfermedades hemic y linfáticas
- Talasemia
- Químicos orgánicos
- Compuestos heterocíclicos, 1 anillo
- Compuestos heterocíclicos
- Compuestos heterocíclicos, 2 anillos
- Compuestos heterocíclicos, anillo fusionado
- Ácidos carboxílicos
- Amidas
- Piperidinas
- Ftalimidas
- Ácidos ftálicos
- Ácidos, carbocíclicos
- Piperidonas
- Isoindoles
- Urea
- Talidomida
- Hidroxiurea
Otros números de identificación del estudio
- Riphah/IIMC/IRB/26/1048
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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