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Immunomodulator

Reduced Toxicity Conditioning for Thalassemia

Phase 1 & 2
Recruiting
Led By KY Chiang, PhD
Research Sponsored by The Hospital for Sick Children
Eligibility Criteria Checklist
Specific guidelines that determine who can or cannot participate in a clinical trial
Must have
Patients with a diagnosis of transfusion dependent beta or alpha thalassemia (3 or 4 gene deletion) between the age of 1-18 years
Patients who are not candidates for gene therapy
Must not have
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. Presence of donor specific antibody (DSA) with mean fluorescence intensity (MFI) greater than 3,000. Previous stem cell transplant or gene therapy. Presence of cardiomyopathy with a T2* < 10ms per Cardiac MRI. 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. Active HIV, hepatitis B or hepatitis C disease. Severe liver cirrhosis or bridging fibrosis on liver biopsy if previously done. Prior or current malignancy or myeloproliferative or immunodeficiency disorder. Evidence of active, deep seated, life-threatening infections despite therapy (e.g., certain fungal species, HIV, etc.). Patients will be excluded if they are women of childbearing potential who are currently pregnant (b-HCG+) or who are not practicing adequate contraception. Any condition that would preclude serial follow up. 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). 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
Timeline
Screening 3 weeks
Treatment Varies
Follow Up day +100 until day +365
Awards & highlights
Approved for 5 Other Conditions
No Placebo-Only Group
All Individual Drugs Already Approved

Summary

This trial is testing a new way to do transplants that may help people with thalassemia who need transfusions.

Who is the study for?
This trial is for kids and teens (1-18 years old) with high-risk thalassemia, which requires regular blood transfusions. They should have a sibling or family donor for bone marrow transplant, not be eligible for gene therapy, and able to take oral meds. Excluded are those with severe organ dysfunction, active infections like HIV/hepatitis B/C, previous transplants or gene therapy, pregnant women or significant allergies to the treatment drugs.
What is being tested?
The study tests a new transplant method using two drugs: Abatacept and Sirolimus in children with thalassemia who need frequent blood transfusions. The goal is to see if this approach can improve long-term outcomes after bone marrow transplantation from family donors.
What are the potential side effects?
Possible side effects of Abatacept and Sirolimus may include increased risk of infection due to immune system suppression, potential liver or kidney problems, allergic reactions, and other drug-specific adverse effects that will be monitored throughout the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
Select...
I am between 1-18 years old and need regular blood transfusions for thalassemia.
Select...
I am not eligible for gene therapy.
Select...
I have a family member who is a match and can donate stem cells to me.
Select...
I have thalassemia with at least one high-risk feature like being over 7, having an enlarged liver, issues with iron removal, severe immune reactions, or can't handle iron removal treatments.
Select...
I can care for myself but cannot carry on normal activity or do active work.
Select...
My thalassemia has been confirmed through genetic testing.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~day +100 until day +365
This trial's timeline: 3 weeks for screening, Varies for treatment, and day +100 until day +365 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.
Primary study objectives
Immune reconstitution
Number of patients who develop Grade II to IV acute GVHD at Day +100
Number of patients who have WBC engraftment by day +100
Secondary study objectives
Number of patients who develop Chronic GVHD
Other study objectives
Cost effectiveness
Length of stay
Number of patients who will wean Sirolimus at 1 year post transplant

Side effects data

From 2023 Phase 3 trial • 657 Patients • NCT03086343
24%
UPPER RESPIRATORY TRACT INFECTION
24%
HYPERTENSION
18%
BRONCHITIS
12%
ACUTE RESPIRATORY FAILURE
12%
RASH
12%
WEIGHT INCREASED
12%
URINARY TRACT INFECTION
12%
INFLUENZA
12%
FALL
12%
ARTHRALGIA
12%
MUSCLE SPASMS
12%
SINUSITIS
12%
CHOLELITHIASIS
12%
NASOPHARYNGITIS
12%
OROPHARYNGEAL PAIN
12%
LIVER FUNCTION TEST INCREASED
6%
VULVOVAGINAL MYCOTIC INFECTION
6%
LIGAMENT RUPTURE
6%
DEHYDRATION
6%
CHRONIC OBSTRUCTIVE PULMONARY DISEASE
6%
NASAL CONGESTION
6%
PULMONARY EMBOLISM
6%
HYPONATRAEMIA
6%
CONSTIPATION
6%
RHINORRHOEA
6%
LEUKOCYTOSIS
6%
BLOOD PRESSURE INCREASED
6%
COUGH
6%
BONE CONTUSION
6%
HIP FRACTURE
6%
VOMITING
6%
PERIPHERAL SWELLING
6%
STAPHYLOCOCCAL INFECTION
6%
ORAL CANDIDIASIS
6%
HERPES ZOSTER
6%
PNEUMONIA
6%
FEELING HOT
6%
HEADACHE
6%
HAEMOGLOBIN DECREASED
6%
PHOTODERMATOSIS
6%
RHEUMATOID ARTHRITIS
6%
PARAESTHESIA
6%
PNEUMONIA BACTERIAL
6%
FEMUR FRACTURE
6%
STOMATITIS
6%
SKIN LACERATION
6%
HYPOKALAEMIA
6%
GLAUCOMA
6%
BACTERIAL SEPSIS
6%
CHEST PAIN
6%
FATIGUE
6%
ATRIOVENTRICULAR BLOCK FIRST DEGREE
6%
CANDIDA INFECTION
6%
TACHYCARDIA
6%
COVID-19
6%
CATARACT
6%
SJOGREN'S SYNDROME
6%
DIZZINESS
6%
DYSPHAGIA
6%
SWELLING
6%
SEBORRHOEIC KERATOSIS
6%
INFECTIOUS PLEURAL EFFUSION
6%
OSTEOARTHRITIS
6%
ACUTE KIDNEY INJURY
6%
NAUSEA
6%
NON-CARDIAC CHEST PAIN
6%
RHINITIS
6%
BLOOD CREATINE PHOSPHOKINASE INCREASED
6%
OSTEOPENIA
6%
INSOMNIA
6%
PRURITUS
6%
SUPRAVENTRICULAR TACHYCARDIA
6%
SCRATCH
6%
EYE HAEMATOMA
6%
ERYTHEMA
6%
COSTOCHONDRITIS
6%
ACTINIC KERATOSIS
6%
DERMATITIS ALLERGIC
6%
ASTHMA
6%
PATELLA FRACTURE
6%
FLANK PAIN
6%
SCIATICA
6%
ANAEMIA
6%
BILIARY COLIC
6%
DERMATITIS CONTACT
6%
HEPATIC STEATOSIS
6%
DRUG HYPERSENSITIVITY
6%
HERPES SIMPLEX
6%
LOCALISED INFECTION
6%
PHARYNGITIS
6%
DIABETES MELLITUS
6%
VITAMIN D DEFICIENCY
6%
BACK PAIN
100%
80%
60%
40%
20%
0%
Study treatment Arm
Period 2, 30 mg Cohort: Upadacitinib 30 mg QD/Upadacitinib 30 mg QD
Period 2, Primary Cohort: Upadacitinib 15 mg QD/Upadacitinib 15 mg QD
Period 2, Primary Cohort: Abatacept/Upadacitinib 15 mg QD
Period 2, 30 mg Cohort: Abatacept/Upadacitinib 30 mg QD/Upadacitinib 15 mg QD
Period 1, 30 mg Cohort: Upadacitinib 30 mg QD
Period 2, 30 mg Cohort: Abatacept/Upadacitinib 30 mg QD
Period 2, 30 mg Cohort: Upadacitinib 30 mg QD/Upadacitinib 30 mg QD/Upadacitinib 15 mg QD
Period 1, Primary and 30 mg Cohorts: Abatacept
Period 1, Primary Cohort: Upadacitinib 15 mg QD

Awards & Highlights

Approved for 5 Other Conditions
This treatment demonstrated efficacy for 5 other conditions.
No Placebo-Only Group
All patients enrolled in this study will receive some form of active treatment.
All Individual Drugs Already Approved
Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Trial Design

1Treatment groups
Experimental Treatment
Group I: PTIS followed by abatacept and sirolimusExperimental Treatment2 Interventions
Administration of reduced-toxicity conditioning regimen combined with pre-transplant immunosuppression, followed by abatacept and sirolimus as graft-versus-host disease (GVHD) prophylaxis for allogeneic transplant with either Human Leukocyte Antigen (HLA)-matched sibling donors or haploidentical donors
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
Abatacept
FDA approved
Sirolimus
FDA approved

Find a Location

Who is running the clinical trial?

The Hospital for Sick ChildrenLead Sponsor
710 Previous Clinical Trials
6,958,165 Total Patients Enrolled
Thalassemia Foundation of CanadaUNKNOWN
KY Chiang, PhDPrincipal InvestigatorThe Hospital for Sick Children

Media Library

Abatacept (Immunomodulator) Clinical Trial Eligibility Overview. Trial Name: NCT05426252 — Phase 1 & 2
Thalassemia Research Study Groups: PTIS followed by abatacept and sirolimus
Thalassemia Clinical Trial 2023: Abatacept Highlights & Side Effects. Trial Name: NCT05426252 — Phase 1 & 2
Abatacept (Immunomodulator) 2023 Treatment Timeline for Medical Study. Trial Name: NCT05426252 — Phase 1 & 2
~6 spots leftby Dec 2025
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