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Recruiting NCT05736419

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)

Phase II Interventional Sickle Cell Disease Thalassemia, Beta Thalassemia

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Fludarabine, Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil.
Who it may be relevant to
Registry conditions: Sickle Cell Disease, Thalassemia, Beta, Thalassemia. Basic parameters: 2 years — 50 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Interventions

  • Drug Fludarabine
    PK-guided fludarabine dosing will be used for each of the 2 cycles, using the InsightRx DoseMeRx platform.
  • Drug Cyclophosphamide
    Cyclophosphamide will be administered Post-Transplant
  • Drug Tacrolimus
    Tacrolimus will be administered beginning on day +5
  • Drug Mycophenolate Mofetil
    Mycophenolate mofetil (MMF) will be administered three times daily starting on day +5.
  • Biological Rabbit ATG
    The dose and schedule of ATG will be determined according to the nomogram in Appendix A
  • Drug Dexamethasone
    Standard Regimen: Dexamethasone on days -68 to -64 and days -40 to -36.
  • Drug Bortezomib
    Bortezomib on days -71, -68, -65, -61, -43, -40, -37, and -33
  • Drug Rituximab
    Rituximab on days -71, -58, -43, and -30.

Primary outcome measures

  • Number of participants with treatment related mortality/TRM or primary graft failure [Time frame: 1 year]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
N/A
Model
Single group
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 6 centers
  • Memorial Sloan Kettering at Basking Ridge (Consent only) — Basking Ridge
  • Memorial Sloan Kettering Monmouth (Consent only) — Middletown
  • Memorial Sloan Kettering Bergen (Consent only) — Montvale
  • Memorial Sloan Kettering Suffolk - Commack (Consent only) — Commack
  • Memorial Sloan Kettering Westchester (Consent only) — Harrison
  • Memorial Sloan Kettering Nassau (All protocol activities) — Rockville Centre

Identifiers

NCT: NCT05736419 · 23-009

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗