Thalassemia
Conditions
Brief summary
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
Detailed description
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.
Interventions
DRUGThalidomide
Tab Thalidomide 0.5 to 4 mg/kg orally every day for 12 months
DRUGHydroxy Urea
Tab Hydroxyurea 10-20 mg/kg per day for 12 months
Sponsors
Riphah International University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is two-arm comparative study. One group is 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 occurred. The starting dose of hydroxyurea will be 10-20 mg/kg per day. Second group will be control group on Blood transfusion.
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in the hemoglobin level | 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 |
| Decrease in transfusion requirement | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Bilirubin levels | 1 year | 0.2- 1.1 mg/dL Normal \>1.1- 3 mg/dL Mild derangement \>3 mg/dL Severe derangement |
| Change in ALT levels | 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 |
| Change in serum creatinine levels | 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 |
| Assess Quality of life by using EORTC QLQ-C30 | 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. |
Countries
Pakistan
Contacts
CONTACTFariha Sardar, MBBS, FCPS
PRINCIPAL_INVESTIGATORFariha Sardar, MBBS, FCPS
Riphah International University, Rwp
Outcome results
None listed