Combination Therapy With Danazol, Prednisolone, and Thalidomide for Thalidomide-Refractory Transfusion-Dependent β-Thalassemia

NCT07884773 | Recruiting Phase 3 DMC

• 1 other identifier: KMU/DIR/CTU/2026/14
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 1

Brief Summary

This study will compare two treatments for children with beta-thalassemia who need regular blood transfusions and have not responded well to thalidomide. One group will continue thalidomide alone. The other group will receive thalidomide plus danazol and prednisolone. The study will check whether the combination treatment reduces the need for blood transfusions, raises hemoglobin levels, and is safe. About 172 children aged 5 to 15 will be assigned by chance to one of the two groups. They will be followed for 9 to 12 months.

Conditions

Beta-Thalassemia; Thalassemia

Keywords

Beta-thalassemia; Transfusion-dependent; Thalidomide-refractory; Combination therapy; Randomized controlled trial

Outcome Measures

Primary Outcomes (3)

• Transfusion independence

  Proportion of participants who remain free from red blood cell transfusion for at least 8 consecutive weeks while maintaining hemoglobin greater than or equal to 9.0 g/dL.

  Assessed continuously from randomization through final study visit (Month 9 to 12).

• Hemoglobin response

  Mean change in pre-transfusion hemoglobin (g/dL) from baseline to 6 months.

  Baseline and Month 6.

• Safety and tolerability

  Incidence and severity of treatment-emergent adverse events, including hepatic toxicity, renal dysfunction, hyperglycemia, peripheral neuropathy, and thromboembolic events, graded according to CTCAE v5.0. Incidence and severity of treatment-emergent adverse events, including hepatic toxicity, renal dysfunction, hyperglycemia, peripheral neuropathy, and thromboembolic events, graded according to CTCAE v5.0. Incidence and severity of treatment-emergent adverse events, including hepatic toxicity, renal dysfunction, hyperglycemia, peripheral neuropathy, and thromboembolic events, graded according to CTCAE v5.0.

  Assessed at every scheduled visit (Months 1, 3, 6, 9, and final visit).

Study Arms (2)

Thalidomide plus Danazol plus Prednisolone

EXPERIMENTAL

In this treatment regimen, Thalidomide and Danazol are administered at a dosage of 100 mg orally three times daily for 30 days each cycle. Prednisolone is given at a dosage of 5 mg orally twice daily for 10 days each month. Supportive care includes Famotidine, folic acid, and vitamin B12. This treatment plan is continued for a duration of 9 to 12 months.

Drug: Thalidomide; Drug: Danazol; Drug: Prednisolone

Thalidomide Monotherapy

ACTIVE COMPARATOR

Thalidomide should be taken orally at a dose of 1 to 5 mg/kg at night, with dosage titrated upward every 2 to 4 weeks based on response and tolerance. Clopidogrel and aspirin should be taken together for thromboprophylaxis. This regimen should continue for 9 to 12 months.

Drug: Thalidomide

Interventions

Danazol DRUG

Oral capsule of 100 mg taken three times daily, continuously for 30 days per cycle. This medication is administered only in the combination arm.

Also known as: Danocrine

Thalidomide plus Danazol plus Prednisolone

Prednisolone DRUG

Oral tablet of 5 mg twice daily for 10 days each month, only administered in the combination arm.

Also known as: Pediapred, Orapred

Thalidomide plus Danazol plus Prednisolone

Thalidomide DRUG

Initial oral capsule dose is 1 to 5 mg/kg taken once daily at night, with adjustments made every 2 to 4 weeks based on response and tolerance. The treatment is administered in both arms for a duration of 9 to 12 months.

Also known as: Thalomid, alpha-(N-phthalimido)glutarimide

Thalidomide Monotherapy; Thalidomide plus Danazol plus Prednisolone

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 5 to 15 years with confirmed transfusion-dependent beta-thalassemia major.
• Documented non-response to adequately dosed thalidomide therapy for at least 6 months.
• Pre-transfusion hemoglobin less than 9.0 g/dL with continued transfusion dependence (more than 2 units per month).
• Adequate baseline clinical and laboratory assessment for safe study treatment.
• Stable transfusion and iron-chelation regimen according to the protocol.
• Written informed consent from parent/legal guardian and age-appropriate assent from the participant, with willingness to comply with study procedures and follow-up.

You may not qualify if:

• Previous allogeneic hematopoietic stem cell or bone marrow transplantation.
• Diabetes mellitus or clinically significant uncontrolled metabolic disease.
• Active severe infection or uncontrolled hepatic, renal, or cardiovascular disease.
• Significant pre-existing peripheral neuropathy or history of clinically significant thromboembolic disease.
• Known hypersensitivity to any study medication.

Sponsors & Collaborators

• Khyber Medical University Peshawar: lead
• Pak International Medical College and Hospital, Peshawar: collaborator
• Peshawar General Hospital: collaborator

Study Sites (1)

Pak International Medical College

Peshawar, Khyber Pakhtunkhwa, 25000, Pakistan

RECRUITING

Related Publications (12)

• Modell B, Darlison M. Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ. 2008 Jun;86(6):480-7. doi: 10.2471/blt.06.036673.

  PMID: 18568278 BACKGROUND

• Weatherall DJ, Clegg JB. Inherited haemoglobin disorders: an increasing global health problem. Bull World Health Organ. 2001;79(8):704-12. Epub 2001 Oct 24.

  PMID: 11545326 BACKGROUND

• Montoto LG, Arregui L, Sanchez NM, Gomendio M, Roldan ER. Postnatal testicular development in mouse species with different levels of sperm competition. Reproduction. 2012 Mar;143(3):333-46. doi: 10.1530/REP-11-0245. Epub 2011 Dec 20.

  PMID: 22187670 BACKGROUND

• Safdari KM, Converse C, Dong F, MacDougall NA, Hyer K, Runyon A, Ahlering H, Comunale ME. Hemodynamic Effects of Methamphetamine and General Anesthesia. Anesthesiol Res Pract. 2022 Feb 17;2022:7542311. doi: 10.1155/2022/7542311. eCollection 2022.

  PMID: 35222639 BACKGROUND

• Ouzaid I, Kammerer-Jacquet SF, Khene Z, Ravaud A, Patard JJ, Bensalah K, Rioux-Leclercq N. Exploring Biological Predictive Factors of Progression After Surgery in High-Risk Renal Cell Carcinoma: Results From the French Cohort of the Randomized S-TRAC Trial Patients. Front Surg. 2020 Jun 5;7:26. doi: 10.3389/fsurg.2020.00026. eCollection 2020.

  PMID: 32582758 BACKGROUND

• Bakathir AA, Moos KF, Ayoub AF, Bagg J. Factors Contributing to the Spread of Odontogenic Infections: A prospective pilot study. Sultan Qaboos Univ Med J. 2009 Dec;9(3):296-304. Epub 2009 Dec 19.

  PMID: 21509313 BACKGROUND

• O'Callaghan J. Russian Moon lander crash - what happened, and what's next? Nature. 2023 Aug 21. doi: 10.1038/d41586-023-02659-6. Online ahead of print. No abstract available.

  PMID: 37604864 BACKGROUND

• Hou X, Zhang P, Du H, Chu W, Sun R, Qin S, Tian Y, Zhang Z, Xu F. Akkermansia Muciniphila Potentiates the Antitumor Efficacy of FOLFOX in Colon Cancer. Front Pharmacol. 2021 Sep 17;12:725583. doi: 10.3389/fphar.2021.725583. eCollection 2021.

  PMID: 34603035 BACKGROUND

• Zywiel M, Ellis K, Veillette CJH, Skou ST, McGlasson R. Implementation of the Good Life with osteoArthritis in Denmark (GLA:D) Program across Canada for the Management of Hip and Knee Osteoarthritis. Healthc Q. 2021 Apr;24(1):54-59. doi: 10.12927/hcq.2021.26464.

  PMID: 33864442 BACKGROUND

• Gelber PE, Drager J, Maheshwer B, Leyes M, Barenius B, Robinson J, Pujol N, Tischer T, Margheritini F, Fritsch B, Frosh KH, Chahla J. Large variability exists in the management of posterolateral corner injuries in the global surgical community. Knee Surg Sports Traumatol Arthrosc. 2020 Jul;28(7):2116-2123. doi: 10.1007/s00167-020-05922-9. Epub 2020 Apr 1.

  PMID: 32239270 BACKGROUND

• Courpied JP, Caton JH. Total Hip Arthroplasty, state of the art for the 21st century. Int Orthop. 2011 Feb;35(2):149-50. doi: 10.1007/s00264-011-1207-9. Epub 2011 Jan 18. No abstract available.

  PMID: 21243356 BACKGROUND

• Nahar R, Zhai W, Zhang T, Takano A, Khng AJ, Lee YY, Liu X, Lim CH, Koh TPT, Aung ZW, Lim TKH, Veeravalli L, Yuan J, Teo ASM, Chan CX, Poh HM, Chua IML, Liew AA, Lau DPX, Kwang XL, Toh CK, Lim WT, Lim B, Tam WL, Tan EH, Hillmer AM, Tan DSW. Elucidating the genomic architecture of Asian EGFR-mutant lung adenocarcinoma through multi-region exome sequencing. Nat Commun. 2018 Jan 15;9(1):216. doi: 10.1038/s41467-017-02584-z.

  PMID: 29335443 BACKGROUND

MeSH Terms

Conditions

beta-Thalassemia; Thalassemia

Interventions

Thalidomide; Danazol; Prednisolone; prednisolone phosphate; Methylprednisolone

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienetriols

Study Officials

• Syeda Nayab Imtiaz, MBBS

  Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar

  PRINCIPAL INVESTIGATOR

• Gulab Fatima Rani, MBBS, PhD

  Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar

  STUDY CHAIR

• Yasar Mehmood Yousafzai, PhD

  Institute of Pathology and Diagnostic Medicine, Khyber Medical University, Peshawar

  STUDY DIRECTOR

Central Study Contacts

Syeda Nayab Imtiaz, MBBS

CONTACT

+923369966014; dr.nayabimtiaz@hotmail.com

Gulab Fatima Rani, MBBS

CONTACT

+923357438822; ranigulabfatima@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This trial is an open-label trial where participants, care providers, and investigators are aware of allocation. Laboratory personnel processing coded specimens and the independent statistician are blinded where feasible. No placebo is used because danazol and prednisolone have no placebo equivalents at the sites.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two-arm, parallel-group, randomized controlled superiority trial. Participants are allocated 1:1 to thalidomide monotherapy or thalidomide plus danazol plus prednisolone. Open-label.

Study Record Dates

• First Submitted: October 13, 2026
• First Posted: October 21, 2026
• Study Start: October 12, 2026
• Primary Completion (Estimated): April 12, 2027
• Study Completion (Estimated): May 20, 2027
• Last Updated: October 21, 2026

Record last verified: 2026-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will become available after publication of the primary results and will remain available for at least 5 years.
• Access Criteria: Access will be granted upon reasonable request to the Principal Investigator, subject to approval by the Institutional Ethics Committee and a signed data-use agreement. Requests must comply with KMU data-sharing policy and patient confidentiality requirements.

Locations

PA (1)