Clinical Experience of Thalidomide in Thalassemic Patients

Efficacy and Safety of Combination of Hydroxyurea and Low-dose Thalidomide on Hemoglobin Synthesis in Thalassemia Patients

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. It was a twelve months study. Participants were monitored for six months on Hydroxyurea alone and then the combination therapy of hydroxyurea and thalidomide for another six months. Findings of physical examination, vital signs, laboratory, and ultrasound findings were recorded at baseline, during and end of the study.

Sample Size and Population This study included 135 Beta-thalassemia patients.

Study Overview

• Status: Completed
• Conditions: Thalassemia, Beta
• Intervention / Treatment: Drug: hydroxyurea and thalidomide

Detailed Description

The purpose of the study was to evaluate the efficacy and safety of the combination therapy of hydroxyurea and thalidomide in beta-thalassemia patients. The participants were evaluated on the basis of eligibility criteria, consent was obtained and baseline investigations were performed on the screening visit. Participants were continued on Hydroxyurea (10-20mg/kg/day) for the first six months and then for the next six months thalidomide (2-5 mg/kg/day) was added to the intervention. Aspirin was also added (2-4mg/kg/day).

Efficacy:

Maintenance or rise in Hemoglobin (Hb) levels and changes in transfusion frequency before and after the use of combination therapy was used to evaluate the efficacy of the combination therapy. Good responders were the patients who were on transfusion and went off-transfusion after the combination therapy or individuals who were already off transfusion and after combination therapy demonstrated an increase in Hb of at least 1gm/dl. Responders were those who remained on transfusion on combination therapy but displayed a 50% reduction in blood requirements. Whereas, non-responders, were individuals who were off-transfusion before combination therapy and had improvement in Hb of <1gm/dl, or those who remained on transfusion during combination therapy and did not experience transfusion reduction of at least 50%.

Safety:

Safety of the drug was evaluated on the basis of the following parameters and 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

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan
      • Children's Hospital Karachi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients with clinical and genetic diagnosis of β-thalassemia major and intermedia
2. Patients who showed partial response or a decline in response to hydroxyurea
3. Patients who are not the candidates for the bone marrow transplant procedure.

Exclusion Criteria:

1. Married Patients
2. Patients with comorbidities such as liver, cerebrovascular, cardiovascular, or kidney diseases
3. Patients allergic to the drug ingredients
4. Patients with mental disorders
5. Patients who are enrolled in other clinical trials
6. Patients with a history of venous or arterial thrombosis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination of hydroxyurea and thalidomide; Hydroxyurea was continued at a dose of 10-20 mg/kg/day for 6 months and then thalidomide was added orally at a dose of 2-5mg/kg/day for 6 months.	Drug: hydroxyurea and thalidomide; Evaluation of hydroxyurea and thalidomide combination use in beta-thalassemia patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in transfusion requirements	Change in transfusion needs (measured as blood volume in ml) per month from baseline	6 months on combination therapy
Change in Hemoglobin levels	Change in hemoglobin level of >1g/dl from baseline	6 months on combination therapy
Change in the liver function test	Change in SGPT in U/l from baseline	6 months on combination therapy
Change in liver function test	Change in total, direct, and indirect bilirubin in mg/dl from baseline	6 months on combination therapy
Change in Kidney Function test	Change in urea and creatinine levels in mg/dl from baseline	6 months on combination therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Spleen size	Change in size of spleen (in centimeters) from baseline	6 months on combination therapy
Change in liver size	Change in size of liver (in centimeters) from baseline	6 months on combination therapy

Collaborators and Investigators

• Sponsor: Children's Hospital Karachi

Publications and helpful links

General Publications

• Ansari SH, Ansari I, Wasim M, Sattar A, Khawaja S, Zohaib M, Hussain Z, Adil SO, Ansari AH, Ansari UH, Farooq F, Masqati NU. Evaluation of the combination therapy of hydroxyurea and thalidomide in beta-thalassemia. Blood Adv. 2022 Dec 27;6(24):6162-6168. doi: 10.1182/bloodadvances.2022007031.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Actual): December 31, 2020
• Study Completion (Actual): January 31, 2021

Study Registration Dates

• First Submitted: October 21, 2021
• First Submitted That Met QC Criteria: November 11, 2021
• First Posted (Actual): November 24, 2021

Study Record Updates

• Last Update Posted (Actual): November 24, 2021
• Last Update Submitted That Met QC Criteria: November 11, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Thalassemia; beta-Thalassemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Leprostatic Agents; Antisickling Agents; Thalidomide; Hydroxyurea
• Other Study ID Numbers: CH-0420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No