RecruitingPhase 2

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)

Pre-Transplant Immune Suppression With Hematopoietic Cell Transplantation From Haploidentical Donors for Adults and Children With Sickle Cell Disease or ß-Thalassemia (Haplo PTCy)

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
2 Years to 50 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Blood draws

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "In addition, depending on the results of participants' routine blood tests, participants may receive the drugs bortezomib and rituximab, which also help with immune suppression."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests drugs that lower the body's immune activity before a donor stem cell transplant. It is for people ages 2 to 50 with sickle cell disease or beta-thalassemia. Researchers want to see if the drugs help prevent the transplant from failing or donor cells from attacking the body.

Hematopoietic Cell Transplantation/HCT involves receiving healthy blood-forming cells (stem cells) from a donor to replace the diseased or damaged cells in participants' bone marrow. The researchers think giving participants treatment with fludarabine and dexamethasone, drugs that lower the activity of the body's immune system (immune suppression), before standard conditioning therapy and HCT may help prevent serious side effects, including graft failure and GvHD. In this study, depending on how participants' body responds to the fludarabine and dexamethasone, the study doctor may decide participants should receive another drug, called cyclophosphamide, instead of fludarabine. In addition, depending on the results of participants' routine blood tests, participants may receive the drugs bortezomib and rituximab, which also help with immune suppression.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be age 2 to 50 and have a suitable donor who is a half match.
  • Meet the study's scores for daily activity and ability to care for yourself or play.
  • Have kidney, liver, heart, and lung test results that meet the study's limits.
  • For sickle cell disease: Have type HbSS, HbSC, or HbS/β° and at least one listed complication. These include repeated chest problems, pain attacks or long-lasting erections; bone infection or damage; stroke or certain brain blood-flow problems; high blood pressure in the lungs; or more than 3 antibodies against donor red blood cells. Some problems must meet set counts or test limits.
  • For beta-thalassemia: Have needed regular red blood cell transfusions starting in the first 3 years of life. Also have more than 15 lifetime transfusions or more than 225 mL/kg per year, hemoglobin of 7 g/dL or less before transfusion, and an enlarged liver and spleen. Hemoglobin carries oxygen in the blood.
  • You or your parent, guardian, or legal representative must give written consent. Children ages 7 to 17 must also agree to take part.
  • If sexually active and able to have children, agree to use birth control approved by the study doctor.

Who can't join

  • Had a donor stem cell transplant using high-dose treatment to destroy bone marrow.
  • Had a stroke with clear symptoms or a procedure involving the brain or spinal cord within the past 6 months.
  • Have severe liver scarring, called cirrhosis, or liver iron of 3 mg per gram of dry liver tissue or higher, if measured. Some mild liver scarring is allowed.
  • Have active hepatitis B or C, or another infection that is not controlled.
  • Have another cancer unless it has been in remission for at least 2 years after treatment. Exceptions include ductal carcinoma in situ, basal cell skin cancer, and abnormal cells on the cervix.
  • Have a positive pregnancy test.
  • Cannot follow the treatment or follow-up plan.
  • Have a known allergy to any part of the stem cell product, including DMSO.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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.

Study sites (6)

NJ

NY