NCT05426252 Thal-Fabs: Reduced Toxicity Conditioning for High Risk Thalassemia
| NCT ID | NCT05426252 |
| Status | Recruiting |
| Phase | Phase 1, Phase 2 |
| Sponsor | The Hospital for Sick Children |
| Condition | Thalassemia in Children |
| Study Type | INTERVENTIONAL |
| Enrollment | 20 participants |
| Start Date | 2022-03-22 |
| Primary Completion | 2025-12-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 20 participants in total. It began in 2022-03-22 with a primary completion date of 2025-12-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
The purpose of this study is to evaluate a novel transplant strategy for the long-term benefit of patients with transfusion dependent high-risk thalassemia.
Eligibility Criteria
Inclusion Criteria: In order to be eligible to participate in this study, the recipient must meet all of the following criteria: 1. Patients with a diagnosis of transfusion dependent beta or alpha thalassemia (3 or 4 gene deletion) between the age of 1-18 years. 2. Thalassemia genotype must be confirmed by molecular genetic testing. 3. Patients with thalassemia must have at least one of the high-risk features: * Age \>7 years * Hepatomegaly (2 cm below costal margin) * Inadequate iron chelation (liver iron content \>7mg/g dry weight) * Severe alloimmunization * Unable to tolerate iron chelation 3\. Patients must have had a complete evaluation of their iron status including measurement of serum ferritin, MRI of the heart and liver (within the previous 6 months prior to referral). Liver elastography (within the preceding 3 months) will be also obtained but not required. 4\. Ability to take oral medication and be willing to adhere to the study regimen. 5\. Patients who have a performance status of at least 70% Karnofsky or Lansky status prior to transplantation. 6\. Patients who are acceptable candidates for marrow transplantation based on their pre-BMT evaluation. 7\. Patients who have histocompatibility sibling or HLA haplo identical family member and have been medically approved as hematopoietic progenitor cell donors. 8\. Patients who are not candidates for gene therapy. 9\. Patients/legal guardians who sign informed consent for the protocol approved by the Research Ethical Board of the Hospital for Sick Children/University of Toronto. Exclusion Criteria: The recipient who meets any of the following criteria will be excluded from participation in this study: 1. Patients will not be excluded based on sex, race, or ethnic background. 2. Patients will be excluded if they demonstrate significant functional deficits in major organs, which could interfere with the outcome following bone marrow transplant, including: * Cardiac: Evidence of significant cardiac dysfunction (resting left ventricular ejection fraction of \< 50% with absence of improvement with exercise), marked cardiomegaly or uncontrollable hypertension. * Renal: Evidence of \> 50% reduction in expected creatinine clearance or GFR \< 60mL/min/1.73m2 * Hepatic: Evidence of hepatic dysfunction evidenced by a serum direct (conjugate) bilirubin of \> 2.5 mg/dl, or ALT \> 5 times the upper limit of normal for age. * Pulmonary: Evidence of focal or diffuse active infection or pneumonitis and the patient demonstrates a FEV1 \< 50% or carbon monoxide diffusing capacity (DLCO) of \< 50% predicted value (adjusted for hemoglobin). The patient should not require ventilation support. 3. Presence of donor specific antibody (DSA) with mean fluorescence intensity (MFI) greater than 3,000. 4. Previous stem cell transplant or gene therapy. 5. Presence of cardiomyopathy with a T2\* \< 10ms per Cardiac MRI. 6. Presence of significant liver iron deposition defined as liver iron content \>15mg/g liver dry weight. If iron chelation were optimized and reassessment within 6 months shows a decrease of LIC to \<15 with no evidence of cardiomyopathy, patient may still be considered for enrollment. 7. Active HIV, hepatitis B or hepatitis C disease. 8. Severe liver cirrhosis or bridging fibrosis on liver biopsy if previously done. 9. Prior or current malignancy or myeloproliferative or immunodeficiency disorder. 10. Evidence of active, deep seated, life-threatening infections despite therapy (e.g., certain fungal species, HIV, etc.). 11. Patients will be excluded if they are women of childbearing potential who are currently pregnant (b-HCG+) or who are not practicing adequate contraception. 12. Any condition that would preclude serial follow up. 13. Patients with a known life-threatening allergy to components of the pre transplant immunosuppression (fludarabine), conditioning (treosulfan, cyclophosphamide or anti-thymocyte globulin) or graft versus host prophylactic regimen (abatacept, sirolimus). 14. Any condition or diagnosis, that could in the opinion of the Principal Investigator or delegate interfere with the participant's ability to comply with study instructions, might confound the interpretation of the study results, or put the participant at risk Donor Eligibility: Donors will not be considered research subjects as the stem cell collection procedure is standard of care and will not be considered part of the research. In order to be eligible to participate in this study, the donor must meet all of the following criteria: 1. May have thalassemia or sickle trait. 2. Will also consider ABO match and lack of donor specific anti-HLA antibodies. 3. Donors must be minimal of 15 kg weight and have completed routine donor evaluations as per our standard of care. 4. Donors must have signed (by patient or legal guardian) informed consent for the protocol approved by the Research Ethical Board of the Hospital for Sick Children/University of Toronto. 5. No evidence of transmissible diseases in compliance with the Health Canada CTO regulations 6. Not pregnant or lactating 7. Must not be allergic to granulocyte colony stimulating factor (G-CSF)
Contact & Investigator
Yogi Chopra, MD
PRINCIPAL INVESTIGATOR
The Hospital for Sick Children
Frequently Asked Questions
Who can join the NCT05426252 clinical trial?
This trial is open to participants of all sexes, aged 1 Year or older, up to 18 Years, studying Thalassemia in Children. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05426252 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT05426252 currently recruiting?
Yes, NCT05426252 is actively recruiting participants. Contact the research team at yogi.chopra@sickkids.ca for enrollment information.
Where is the NCT05426252 trial being conducted?
This trial is being conducted at Toronto, Canada.
Who is sponsoring the NCT05426252 clinical trial?
NCT05426252 is sponsored by The Hospital for Sick Children. The principal investigator is Yogi Chopra, MD at The Hospital for Sick Children. The trial plans to enroll 20 participants.