Thalassemia, BetaPhase 2/3NCT06153784
Thalidomide and Hydroxyurea Combination in β-Thalassemia Patients
A Phase 2/3 study testing Hydroxyurea and Thalidomide in people with Thalassemia, Beta, run by Children's Hospital Karachi at 1 site in Pakistan.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 50 years
- Conditions the study is for
- Thalassemia, Beta
- What is being tested?
- Hydroxyurea and Thalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 603 participants
- Where
- 1 sitePakistan
- Study dates
- 7 Jul 2020to 30 Jul 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 50 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with clinical and genetic diagnoses of β-thalassemia major and intermedia
- Patients who showed partial response or a decline in response to hydroxyurea
- Patients who are not candidates for the bone marrow transplant procedure
Who cannot join
- Married Patients
- Patients with comorbidities such as liver, cerebrovascular, cardiovascular, or kidney diseases
- Patients allergic to the drug ingredients
- Patients with mental disorders
- Patients who are enrolled in other clinical trials
- Patients with a history of venous or arterial thrombosis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Long-Term Assessment of Thalidomide and Hydroxyurea Combination Therapy in β-Thalassemia Patients
Objectives
Primary objective:
Read more
- 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."
Read the 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
- Conditions
- Thalassemia, Beta
- Being tested
- Hydroxyurea and Thalidomide
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hydroxyurea and ThalidomideDrug
Evaluation of hydroxyurea and thalidomide combination use in beta-thalassemia patients
| Study group | Role | What they receive |
|---|---|---|
| Combination of hydroxyurea and thalidomide | Experimental | 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. Receives: Drug: Hydroxyurea and Thalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response at different time intervals
Frequency of good responder, responder, and non-responder.
Measured: 1-3 years on combination therapy
Change in laboratory levels
Mean changes in hemoglobin, platelets, leukocytes, urea, creatinine, and ferritin level from baseline
Measured: 1-3 years on combination therapy
Change in the liver and spleen size
Mean changes in the liver and spleen size from baseline
Measured: 1-3 years on combination therapy
Secondary outcomes (1)
XmnI polymorphism
Comparison of XmnI polymorphism with outcome among patients who completed 1-year, 2-years, and 3-years of combination therapy
Measured: 1-3 years on combination therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Dec 2023
- Study start7 Jul 2020
- Primary completion30 Jul 2023
- Study completion30 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thalassemia, BetaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 603 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Karachi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Saqib H Ansari, Phd, Principal investigator, Children's Hospital Karachi Sindh, Pakistan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06153784
- Sponsor's protocol ID
- CH-0428
- Status last verified
- Nov 2023
- First submitted
- 23 Nov 2023
- Last updated
- 1 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long-Term Assessment of Thalidomide and Hydroxyurea Combination Therapy in β-Thalassemia Patients
- ClinicalTrials.gov ID
- NCT06153784
- Acronym / sponsor ID
- CH-0428
- Conditions
- Thalassemia, Beta
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 603 participants (actual)
- Lead sponsor
- Children's Hospital KarachiUniversity, hospital or other
- Study start
- 7 Jul 2020 (actual)
- Primary completion
- 30 Jul 2023 (actual)
- Study completion
- 30 Jul 2023 (actual)
- First posted
- 1 Dec 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination of hydroxyurea and thalidomide | Experimental | Drug: Hydroxyurea and ThalidomideHydroxyurea 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. |
Who may qualify
- Ages
- 2 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Patients with clinical and genetic diagnoses of β-thalassemia major and intermedia
- Patients who showed partial response or a decline in response to hydroxyurea
- Patients who are not candidates for the bone marrow transplant procedure
Key exclusion criteria (6 listed)
- Married Patients
- Patients with comorbidities such as liver, cerebrovascular, cardiovascular, or kidney diseases
- Patients allergic to the drug ingredients
- Patients with mental disorders
- Patients who are enrolled in other clinical trials
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hydroxyurea and ThalidomideEvaluation of hydroxyurea and thalidomide combination use in beta-thalassemia patients | Drug | Combination of hydroxyurea and thalidomide |
Primary outcome
Response at different time intervals
Time frame: 1-3 years on combination therapy
Frequency of good responder, responder, and non-responder.
Change in laboratory levels
Time frame: 1-3 years on combination therapy
Mean changes in hemoglobin, platelets, leukocytes, urea, creatinine, and ferritin level from baseline
Change in the liver and spleen size
Time frame: 1-3 years on combination therapy
Mean changes in the liver and spleen size from baseline
1 secondary outcome
XmnI polymorphism
Time frame: 1-3 years on combination therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Dec 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saqib H Ansari, Phd principal investigator
Children's Hospital Karachi Sindh, Pakistan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Hydroxyurea and Thalidomide in people with Thalassemia, Beta, run by Children's Hospital Karachi at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Response at different time intervals (time frame: 1-3 years on combination therapy). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Dec 2023.