Recruiting

Phase 2

Immune SuppressionA 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)

Sponsor:

Memorial Sloan Kettering Cancer Center

Code:

NCT05736419

Conditions

Sickle Cell Disease

Thalassemia, Beta

Thalassemia

Eligibility Criteria

Sex: All

Age: 2 - 50

Healthy Volunteers: Not accepted

Interventions

Fludarabine

Cyclophosphamide

Tacrolimus

Mycophenolate Mofetil

Rabbit ATG

Study Details

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.

Conditions

Sickle Cell Disease

Thalassemia, Beta

Thalassemia

Study ID

NCT05736419

Start date

Feb 9, 2023

Status verified date

Jun, 2026

Completion date

Feb 9, 2027

Anticipated

Primary completion date

Feb 9, 2027

Anticipated

Eligibility Criteria

Sex: All

Age: 2 - 50

Healthy Volunteers: Not accepted

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 Design

Enrollment

24 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Participants with Sickle Cell Disease or β-Thalassemia

Participants will have severe sickle cell disease or transfusion-dependent β-thalassemia.

Interventions

Fludarabine

PK-guided fludarabine dosing will be used for each of the 2 cycles, using the InsightRx DoseMeRx platform.

Cyclophosphamide

Cyclophosphamide will be administered Post-Transplant

Tacrolimus

Tacrolimus will be administered beginning on day +5

Mycophenolate Mofetil

Mycophenolate mofetil (MMF) will be administered three times daily starting on day +5.

Rabbit ATG

The dose and schedule of ATG will be determined according to the nomogram in Appendix A

Dexamethasone

Standard Regimen: Dexamethasone on days -68 to -64 and days -40 to -36.

Bortezomib

Bortezomib on days -71, -68, -65, -61, -43, -40, -37, and -33

Rituximab

Rituximab on days -71, -58, -43, and -30.

Primary outcome measure

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

Central Contacts and Locations

Central contacts

Maria Cancio, MD

212-639-2446 canciom@mskcc.org

Jaap Jan Boelens, MD, PhD

212-639-3643 boelensj@mskcc.org

Locations

Memorial Sloan Kettering at Basking Ridge (Consent only)

Recruiting

Basking Ridge, New Jersey, United States, 07920

Contacts

Maria Cancio, MD

212-639-2446

Memorial Sloan Kettering Monmouth (Consent only)

Recruiting

Middletown, New Jersey, United States, 07748

Contacts

Maria Cancio, MD

212-639-2446

Memorial Sloan Kettering Bergen (Consent only)

Recruiting

Montvale, New Jersey, United States, 07645

Contacts

Maria Cancio, MD

212-639-2446

Memorial Sloan Kettering Suffolk - Commack (Consent only)

Recruiting

Commack, New York, United States, 11725

Contacts

Maria Cancio, MD

212-639-2446

Memorial Sloan Kettering Westchester (Consent only)

Recruiting

Harrison, New York, United States, 10604

Contacts

Maria Cancio, MD

212-639-2446

Memorial Sloan Kettering Nassau (All protocol activities)

Recruiting

Rockville Centre, New York, United States, 11553

Contacts

Maria Cancio, MD

212-639-2446

More Information

Sponsor

Memorial Sloan Kettering Cancer Center

Last update posted

Jun 3, 2026

Last verified

Jun, 2026

Keywords

allogeneic hematopoietic cell transplantation
Sickle Cell Disease
Beta Thalassemia
Thalassemia
23-009
Memorial Sloan Kettering Cancer Center

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Memorial Sloan Kettering Cancer Center on 2026-06-03.