Clinical trial 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)
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Sickle Cell Disease
Thalassemia, Beta
Thalassemia
Keywords: allogeneic hematopoietic cell transplantation
Sickle Cell Disease
Beta Thalassemia
Thalassemia
23-009
Memorial Sloan Kettering Cancer Center
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2023-02-21
Enrollment: 24
Sex: ALL
Minimum age (years): 2
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: Number of participants with treatment related mortality/TRM or primary graft failure
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Basking Ridge
country: United States
facility: Memorial Sloan Kettering at Basking Ridge (Consent only)
state: New Jersey
city: Middletown
country: United States
facility: Memorial Sloan Kettering Monmouth (Consent only)
state: New Jersey
city: Montvale
country: United States
facility: Memorial Sloan Kettering Bergen (Consent only)
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Suffolk - Commack (Consent only)
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Westchester (Consent only)
state: New York
city: Rockville Centre
country: United States
facility: Memorial Sloan Kettering Nassau (All protocol activities)
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Maria Cancio, MD
role: PRINCIPAL_INVESTIGATOR
References: