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
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Antatt)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiekontakt
- Navn: Fariha Sardar, MBBS, FCPS
- Telefonnummer: +923335517877
- E-post: doc.fariha@yahoo.com
Studer Kontakt Backup
- Navn: Fariha Sardar, MBBS, FCPS
- Telefonnummer: +923350941494
- E-post: afzaal2kmt20@gamil.com
Studiesteder
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Punjab Province
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Rawalpindi, Punjab Province, Pakistan
- Rekruttering
- Riphah International University
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Ta kontakt med:
- Fariha Sadar, MBBS, FCPS
- Telefonnummer: +923335517877
- E-post: doc.fariha@yahoo.com
-
Ta kontakt med:
- Fariha Saradr, MBBS, FCPS
- Telefonnummer: +923350941494
- E-post: afzaal2kmt20@gamil.com
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
- Barn
- Voksen
- Eldre voksen
Tar imot friske frivillige
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Ingen inngripen: Blood transfusion Group
Control group will be on regular blood transfusion and iron chelation therapy
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Eksperimentell: 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
Andre navn:
Tab Hydroxyurea 10-20 mg/kg per day for 12 months
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Improvement in the hemoglobin level
Tidsramme: 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
Tidsramme: 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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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Serum Bilirubin levels
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Hovedetterforsker: Fariha Sardar, MBBS, FCPS, Riphah International University, Rwp
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Genetiske sykdommer, medfødte
- Hematologiske sykdommer
- Anemi, hemolytisk, medfødt
- Anemi, hemolytisk
- Anemi
- Hemoglobinopatier
- Medfødte, arvelige og neonatale sykdommer og abnormiteter
- Hemic og lymfatiske sykdommer
- Thalassemi
- Organiske kjemikalier
- Heterocykliske forbindelser, 1-ring
- Heterocykliske forbindelser
- Heterocykliske forbindelser, 2-ring
- Heterocykliske forbindelser, smeltet ringen
- Karboksylsyrer
- Amides
- Piperidines
- Ftalimider
- Ftalsyrer
- Syrer, karbosykliske
- Piperidoner
- Isoindoles
- Urea
- Thalidomid
- Hydroxyurea
Andre studie-ID-numre
- Riphah/IIMC/IRB/26/1048
Plan for individuelle deltakerdata (IPD)
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