NCT03653338 T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias
| NCT ID | NCT03653338 |
| Status | Recruiting |
| Phase | Phase 1, Phase 2 |
| Sponsor | Paul Szabolcs |
| Condition | Sickle Cell Anemia |
| Study Type | INTERVENTIONAL |
| Enrollment | 5 participants |
| Start Date | 2018-08-02 |
| Primary Completion | 2026-08-01 |
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 5 participants in total. It began in 2018-08-02 with a primary completion date of 2026-08-01.
⚠ 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 what effect, if any, mismatched unrelated volunteer donor and/or haploidentical related donor stem cell transplant may have on severe sickle cell disease and other transfusion dependent anemias. By using mismatched unrelated volunteer donor and/or haploidentical related donor stem cells, this study will increase the number of patients who can undergo a stem cell transplant for their specified disease. Additionally, using a T-cell depleted approach should reduce the incidence of graft-versus-host disease which would otherwise be increased in a mismatched transplant setting.
Eligibility Criteria
Inclusion Criteria 1. Patient, parent, or legal guardian must have given written informed consent and/or assent according to FDA guidelines. 2. Ages 5 years to 40 years, at time of consent. 3. Diagnosis of Sickle Cell Disease (Hemoglobin SS, Sβ0-thalassemia) complicated by any of the following: * Recurrent acute painful episodes (also known as vaso-occlusive crises; VOC) despite supportive care, minimum of 2 new pain events per year requiring hospitalization for parenteral pain management in the previous 2 years. * Recurrent acute chest syndrome (ACS) despite supportive care, minimum of 2 episodes in preceding 2-year period. * Stroke or neurologic event lasting \> 24 hours with an accompanying infarct on MRI in any patient for all ages; Brain MRI with silent infarct without clinical event in patients ≤ 16 years. * Chronic transfusion therapy defined as \> 8 packed red blood cell transfusions per year in the year prior to enrollment and/or evidence of red blood cell alloimmunization. * Elevated transcranial Doppler velocities - \> 200 cm/s, via the non-imaging technique or \> 185 cm/s by the imaging technique measured on 2 separate occasions ≥ 1-month apart * Elevated TRV \> 2.6m/s in patients ≥ 16 years old. * Sickle-related renal insufficiency and/or sickle hepatopathy and/or any irreversible end-organ damage in patients ≥ 16 years old. OR Diagnosis of beta-thalassemia or Diamond-Blackfan anemia complicated by transfusion dependence with evidence of iron overload. 4. A minimum donor match of 4/8 via high resolution HLA typing at HLA-A, -B, -C, -DRB1 loci in the related setting or minimum donor match of 6/8 via high resolution HLA typing at HLA-A, -B, -C, -DRB1 loci (with the DRB1 locus as a full match requirement). An unrelated donor and cord blood search must have been completed without an eligible 8/8 matched unrelated donor or 6/8 cord blood unit available. Patients who may have acceptable cord blood donor options (4/6 or better) but are limited by cell dose of a single cord will also be eligible for the proposed study. 5. Adequate function of other organ systems as measured by: * Creatinine clearance or GFR ≥ 45 ml/min/1.73m. * Hepatic transaminases (ALT/AST) ≤ 3 x upper limit of normal. * Liver MR imaging for iron content should be performed in all patients with Ferritin \> 500 ng/mL. If hepatic iron content \> 10mg Fe/g liver should have hepatology consultation and liver biopsy to confirm absence of cirrhosis, fibrosis or hepatitis. * Adequate cardiac function as measure by echocardiogram (shortening fraction \> 26% or ejection fraction \> 40% or \>80% of age-specific normal). * Pulmonary evaluation testing demonstrating FEV1/FVC ≥ 60% of predicted for age and/or resting pulse oximeter ≥ 92% on room air. * Cardiology clearance to proceed with conditioning regimen and HSCT. * Pulmonology clearance to proceed with conditioning regimen and HSCT. 6. Subjects must be human immunodeficiency virus (HIV) negative by PCR. 7. Negative pregnancy test for females ≥10 years old or who have reached menarche, unless surgically sterilized. 8. All females of childbearing potential and sexually active males must agree to use an FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect. 9. Subject and/or parent guardian will also be counseled regarding the potential risks of infertility following BMT and advised to discuss sperm banking or oocyte harvesting (Refer to section, 10. Hydroxyurea must have been trialed and failed in patients with sickle cell disease. Patient Exclusion Criteria 1. Patients with alternate, superior donor options (matched sibling donor or matched unrelated donor). 2. Patients who have undergone stem cell transplantation in the 6 months prior to anticipated conditioning. 3. Patients with history of a central nervous system (CNS) event within six months prior to start of conditioning (patient will be delayed until eligible). 4. Patients who are pregnant or lactating 5. Patients with uncontrolled bacterial, viral or fungal infection 6. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.
Contact & Investigator
Paul Szabolcs, MD
PRINCIPAL INVESTIGATOR
University of Pittsburgh
Frequently Asked Questions
Who can join the NCT03653338 clinical trial?
This trial is open to participants of all sexes, aged 5 Years or older, up to 40 Years, studying Sickle Cell Anemia. 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 NCT03653338 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 NCT03653338 currently recruiting?
Yes, NCT03653338 is actively recruiting participants. Contact the research team at paul.szabolcs@chp.edu for enrollment information.
Where is the NCT03653338 trial being conducted?
This trial is being conducted at Pittsburgh, United States.
Who is sponsoring the NCT03653338 clinical trial?
NCT03653338 is sponsored by Paul Szabolcs. The principal investigator is Paul Szabolcs, MD at University of Pittsburgh. The trial plans to enroll 5 participants.
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