Thalidomide and Hydroxyurea Combination in β-Thalassemia Patients
Condition: Thalassemia, Beta
MeSH terms: Thalassemia; beta-Thalassemia
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Objectives

      Primary objective:

      • To determine the efficacy and safety of the combination therapy of Hydroxyurea and
      thalidomide in beta-thalassemia patients.

      Secondary objective:

      • To determine the change in liver and spleen size of beta-thalassemia patients on the
      combination therapy.

      A single-arm non-randomized trial to evaluate the efficacy and safety of combination therapy
      of hydroxyurea and thalidomide in beta-thalassemia patients. Participants were monitored for
      six months on Hydroxyurea alone and then the combination therapy of hydroxyurea and
      thalidomide was started. Findings of physical examination, vital signs, laboratory, and
      ultrasound findings were recorded at baseline, during, and end of the study.

      The assessment of treatment outcomes was conducted at the 1-year, 2-year, and 3-year
      follow-up points during the combination therapy period, categorizing patients as either "good
      responders," "responders," or "non-responders."
    

Detailed description: 
      This study is conducted to evaluate the long-term efficacy and safety of the combination
      therapy of hydroxyurea and thalidomide in beta-thalassemia patients.

      Monotherapy of Hydroxyurea was sustained at a daily dosage ranging from 10-20 mg/kg for a
      duration of 6 months, during which the treatment response was documented. After this initial
      6-month period, thalidomide was introduced into the treatment regimen. Thalidomide was
      administered orally at bedtime, with an initial dosage of 2-5 mg/kg. An incremental dosing
      approach was employed for thalidomide, with individuals who exhibited an insufficient
      response to lower doses having their dosage increased to a maximum of 5 mg/kg. Additionally,
      aspirin was prescribed at a daily dosage of 2-4 mg/kg to mitigate the risk of thrombosis.

      Blood transfusions were administered under specific conditions throughout the study.
      Transfusions were initiated if the Hb levels dropped below 7 g/dL or if patients exhibited
      symptoms or instability, regardless of their Hb levels. Patients who were undergoing iron
      chelation therapy (utilizing deferasirox, deferiprone, and/or deferoxamine) while on HU
      monotherapy continued this regimen throughout the combination therapy phase.

      Throughout combination therapy, various assessments were conducted and documented, including
      blood transfusion events and comprehensive blood count evaluations, carried out at baseline,
      as well as during the 1-year, 2-year, and 3-year follow-up periods. Concurrently, safety
      parameters, such as urea and creatinine levels, liver function tests, and measurements of
      liver and spleen size, were consistently monitored and recorded.

      Outcome:

      Good responders were characterized as individuals who were previously reliant on blood
      transfusions while on hydroxyurea therapy but became transfusion-independent after the
      initiation of hydroxyurea and thalidomide combination therapy. Furthermore, patients who were
      already free from transfusions while on hydroxyurea therapy and demonstrated an increase in
      Hb levels exceeding 1 g/dL upon combination therapy were also classified as good responders.

      Responders were defined as patients who, while receiving blood transfusions during
      hydroxyurea therapy, exhibited a substantial reduction of at least 50% in the volume of PRC
      transfusions over a span of 6 months after the onset of combination therapy.

      Non-responders encompassed patients who were not reliant on transfusions during hydroxyurea
      therapy but did not display any significant enhancement in Hb levels following the
      commencement of combination therapy. Additionally, individuals who were dependent on
      transfusions but experienced less than a 50% reduction in PRC transfusion volume despite
      hydroxyurea and thalidomide combination therapy were also categorized as non-responders.

      Safety:

      The safety of the drug was evaluated based on the following parameters and the intervention
      was discontinued or put on hold if:

        -  Creatinine >1.1mg/dl, Urea >43mg/dl),

        -  Liver function (SGPT >35mg/L)

        -  Absolute Neutrophil counts<2*109/L

        -  Platelets < 100*109/L
    

Intervention name(s): Hydroxyurea and Thalidomide
Intervention type(s): Drug
Intervention description(s): Evaluation of hydroxyurea and thalidomide combination use in beta-thalassemia patients
Intervention MeSH terms: Thalidomide; Hydroxyurea
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment