A Study of Immune Suppression Treatment for People With Sickle Cell Disease or β-Thalassemia Who Are Going to Receive an Allogeneic Hematopoietic Cell Transplantation (HCT)

Launched by MEMORIAL SLOAN KETTERING CANCER CENTER · Feb 17, 2023

Keywords

ClinConnect Summary

This clinical trial is investigating a new treatment approach for individuals with Sickle Cell Disease or β-Thalassemia who are preparing to receive a stem cell transplant from a donor. The goal is to see if using medications that reduce the immune system's activity, specifically fludarabine and dexamethasone, before the transplant can help prevent serious complications like graft failure (when the new cells don’t take hold) and graft-versus-host disease (when the donor cells attack the recipient's body). Depending on how participants respond, doctors may adjust the medications given.

To join the trial, participants need to be between 12 and 35 years old and have a suitable donor available. They should also meet certain health criteria, such as having good organ function and specific complications related to their condition, like frequent pain episodes or severe anemia. Those who participate can expect close monitoring during the treatment, which may include various medications to help manage their immune system. It's important for potential participants and their families to discuss any questions or concerns with their healthcare team to understand how this trial might help them.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Age \> 12 and \< 35 years. Patients of age 2-12 and 35-50 years will be included after 8 patients reach day 100 without TRM and if ≥ 4 of the first 8 patients reach day 100 without graft failure or grade III-IV acute GvHD.
• • Suitable haploidentical donor.
• • Performance score ≥ 70% by Karnofsky Performance Scale or 0 to 1 by ECOG (age \> 16 years), or Lansky Play-Performance Scale ≥ 70% (age ≤ 16 years).
• * Adequate major organ system function as demonstrated by:
• * For patients ≥ 18 years of age:
• • eGFR ≥ 50 mL/min by Cockcroft-Gault formula
• * For patients \< 18 years of age:
• • Serum creatinine clearance: glomerular filtration rate \[GFR\]) must be \>50 mL/min/1.73 m2 as calculated by the Schwartz formula
• • Conjugated (direct) bilirubin less than 2x upper limit of normal.
• • ALT or AST ≤ 3 times institutional upper limit of normal.
• • Left ventricular ejection fraction ≥ 50%.
• • Diffusing capacity for carbon monoxide (DLCO) ≥ 50% predicted, corrected for hemoglobin. For children \< 7 years of age who are unable to perform PFT, oxygen saturation \> 92% on room air by pulse oximetry.
• * For SCD patients: HbSS, HbSC, HbS/β° with one or more of the following complications:
• • Acute chest syndrome: 2 or more episodes in the 2 years preceding enrollment
• • Vaso-occlusive episodes: 3 or more episodes in the 2 years preceding enrollment
• • Recurrent priapism: 2 or more episodes in the 2 years preceding enrollment
• • History of osteomyelitis or osteonecrosis
• * Cerebrovascular disease:
• • Imaging evidence of prior overt or silent stroke
• • History of a neurologic event resulting in focal neurologic deficits lasting \> 24 hours
• • Abnormal transcranial Doppler: Timed average maximum mean velocity ≥ 200 cm/sec in terminal portion of the carotid or proximal portion of the middle cerebral artery or \> 185 cm/sec plus evidence of intracranial vasculopathy if imaging TCD is used
• • Pulmonary hypertension: Confirmed by right heart catheterization with mean pulmonary arterial pressure ≥ 25 mmHg or mean pulmonary vascular resistance \> 2 Wood units
• • Red blood cell alloimmunization (\> 3 alloantibodies)
• * For thalassemia patients: Any genotype, with all of the following:
• • Onset of red blood cell transfusion dependence during the first 3 years of life
• • RBC transfusion history \> 225 mL/kg/year or \> 15 lifetime RBC transfusions
• • Pre-transfusion hemoglobin ≤ 7 g/dL
• • Hepatosplenomegaly
• • Patient or the patient's legal representative, parent(s) or guardian should be able to provide written informed consent. Assent of a minor if participant's age is at least seven and less than eighteen years.
• • For sexually active men and women of childbearing potential, must agree to use a form of contraception considered effective and medically acceptable by the Investigator.
• Exclusion Criteria:
• • Prior myeloablative allogeneic HCT.
• • Overt stroke or CNS instrumentation (e.g. for Moyamoya disease) within 6 months of enrollment.
• • Liver cirrhosis. Mild fibrosis will be permitted, i.e. fine reticulin or grade 1 of 4, with bridging fibrosis.
• • Hepatic iron content ≥ 3 mg Fe/g liver dry weight
• • HIV positive
• • Active hepatitis B or C.
• • Other uncontrolled infections.
• • BMI \> 40.
• • Other malignancy/cancer diagnosis unless in remission after definitive therapy for a minimum of 2 years. Exceptions: Ductal carcinoma in situ, basal cell carcinoma, cervical intraepithelial neoplasia.
• • Positive pregnancy test in a woman with child-bearing potential, defined as not post-menopausal for 12 months or no previous surgical sterilization.
• • Inability to comply with medical therapy or follow-up.
• • Known history of allergic reactions to any constituents of the cell product, including a known history of allergic reactions to DMSO.