Immune suppression treatment for sickle cell disease and beta-thalassemia patients receiving stem cell transplants
Pre-Transplant Immune Suppression With Hematopoietic Cell Transplantation From Haploidentical Donors for Adults and Children With Sickle Cell Disease or ß-Thalassemia (Haplo PTCy)
This study is testing if a new immune suppression treatment can help people with sickle cell disease or beta-thalassemia have better outcomes when they receive stem cell transplants.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 2 Years to 50 Years |
| Sex | All |
| Sponsor | Memorial Sloan Kettering Cancer Center Academic / other |
| Drugs / interventions | rituximab, cyclophosphamide, fludarabine |
| Locations | 6 sites (Basking Ridge, New Jersey and 5 other locations) |
| Trial ID | NCT05736419 on ClinicalTrials.gov |
What this trial studies
This study investigates the use of immune suppression treatment with fludarabine and dexamethasone in patients with sickle cell disease or beta-thalassemia who are preparing for allogeneic hematopoietic cell transplantation (HCT). The goal is to reduce the risk of serious complications such as graft failure and graft-versus-host disease (GvHD) by administering these drugs before standard conditioning therapy. Depending on individual responses, participants may also receive cyclophosphamide, bortezomib, and rituximab to enhance immune suppression. The study aims to evaluate the safety and efficacy of this approach in improving transplant outcomes.
Who should consider this trial
Good fit: Ideal candidates are individuals aged 12 to 35 years with sickle cell disease or beta-thalassemia who have a suitable haploidentical donor and meet specific health criteria.
Not a fit: Patients outside the age range of 2 to 50 years or those without a suitable donor may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could significantly improve transplant success rates and reduce complications for patients with sickle cell disease and beta-thalassemia.
How similar studies have performed: Other studies have shown promise with similar immune suppression approaches in hematopoietic cell transplantation, indicating potential for success.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * Age ≥ 2 and ≤ 50 years * 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 Formula: ((140 - Age) x Weight (kg)) / (72 x Serum Creatinine (mg/dL) Female Adjustment: Multiply result by 0.85 * 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 3x 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, if applicable * Active hepatitis B or C. * Other uncontrolled infections. * 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 stem cell product, including a known history of allergic reactions to DMSO.
Where this trial is running
Basking Ridge, New Jersey and 5 other locations
- Memorial Sloan Kettering at Basking Ridge (Consent only) — Basking Ridge, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Monmouth (Consent only) — Middletown, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Bergen (Consent only) — Montvale, New Jersey, United States (Recruiting)
- Memorial Sloan Kettering Suffolk - Commack (Consent only) — Commack, New York, United States (Recruiting)
- Memorial Sloan Kettering Westchester (Consent only) — Harrison, New York, United States (Recruiting)
- Memorial Sloan Kettering Nassau (All protocol activities) — Rockville Centre, New York, United States (Recruiting)
Study contacts
- Principal investigator: Maria Cancio, MD — Memorial Sloan Kettering Cancer Center
- Study coordinator: Maria Cancio, MD
- Email: canciom@mskcc.org
- Phone: 212-639-2446
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.