Sickle Cell Anemia Clinical Trial
Official title:
T-Cell Depleted, Alternative Donor Transplant in Pediatric and Adult Patients With Severe Sickle Cell Disease (SCD) and Other Transfusion-Dependent Anemias
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.
Status | Recruiting |
Enrollment | 5 |
Est. completion date | August 1, 2026 |
Est. primary completion date | August 1, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 5 Years to 40 Years |
Eligibility | 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, Sß0-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. |
Country | Name | City | State |
---|---|---|---|
United States | Children's Hospital of Pittsburgh of UPMC | Pittsburgh | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Paul Szabolcs |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Graft rejection | How frequent, if any, graft rejection occurs | Day -30 through study completion, an average of 2 years | |
Primary | Post Transplant treatment related mortality | Number of deaths that occurred from treatment | By day 100 | |
Primary | Acute Graft versus host disease | The number of patients who develop acute graft versus host disease (GVHD)post transplant | Day 0 through study completion, an average of 2 years | |
Primary | Chronic Graft versus host disease | The number of patients who develop chronic graft versus host disease (GVHD) post transplant | Day 0 through study completion, an average of 2 years | |
Primary | Post Transplant treatment related mortality | Number of deaths that occurred from treatment | Day 180 | |
Primary | Post Transplant treatment related mortality | Number of deaths that occurred from treatment | 1 year | |
Secondary | Neutrophil recovery | = 0.5 x 103/µL neutrophils for three consecutive days tested on different days. | Day 0 through study completion, an average of 2 years | |
Secondary | Donor Cell Engraftment | = 5% donor cells on day +42 and = 10% donor cells on day +100. We will record if subjects have attained robust donor cell engraftment (> 50% donor chimerism at 180 days). | From Day 0, Day 42, Day 100 and Day 180. Further testing can be done if clinically indicated up to 2 years post transplant | |
Secondary | Neurological complications | To evaluate the incidence of neurological complications | Day 0 through study completion, an average of 2 years | |
Secondary | Immune reconstitution | The pace of systemic immune reconstitution | Day 0 through study completion, an average of 2 years | |
Secondary | Cytomegalovirus (CMV) infection | Incidence of CMV infection by Polymerase chain reaction (PCR) as clinically indicated | Day 0 through study completion, an average of 2 years | |
Secondary | Donor Lymphocyte Infusions response | Evaluate for delayed immune reconstitution, mixed chimerism or viral reactivation | Day 0 through study completion, an average of 2 years | |
Secondary | Response to donor-derived virus-specific cytotoxic T-cell therapy | Activation or reactivation of Cytomegalovirus (CMV), Epstein-Barr Virus (EBV) or adenovirus testing by PCR | Day 0 through study completion, an average of 2 years | |
Secondary | Sickle Cell disease phenotype recurrence | The incidence of Sickle Cell recurrence as clinical evidence of vaso occlusive crisis, detection of HgbS>25% and acute chest syndrome. | Day 0 through study completion, an average of 2 years | |
Secondary | Recurrence of transfusion-dependence | 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. | Day 0 through study completion, an average of 2 years | |
Secondary | Organ toxicity | Incidence of Grade 3-4 | Day 0 through study completion, an average of 2 years | |
Secondary | Long-term complications-Sterility, endocrinopathy, and secondary malignancy | Incidence of long term complications | Day 0 through study completion, an average of 2 years | |
Secondary | Pediatric Quality of Life Inventory | Measures Pain/Hurt ,Pain Impact,Pain Management/Control ,Worry ,Emotions ,Treatment , Communication | Baseline through study completion, an average of 2 years | |
Secondary | Platelet Recovery | Platelet count of = 20,000/µL without platelet transfusion in the previous 7 days. | Day 0 through study completion, an average of 2 years | |
Secondary | Adult Sickle Cell Quality of Life Measurement System (ASCQ) | Patient reported outcome measurement system that assesses the physical, social and emotional impact of Sickle Cell Disease. | Baseline through study completion, an average of 2 years |
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