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)

NCT ID: NCT05736419

Last Updated: 2025-05-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-09

Study Completion Date

2026-02-09

Brief Summary

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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.

Detailed Description

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Conditions

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Sickle Cell Disease Thalassemia, Beta Thalassemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Participants with Sickle Cell Disease or β-Thalassemia

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

Group Type EXPERIMENTAL

Fludarabine

Intervention Type DRUG

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

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be administered Post-Transplant

Tacrolimus

Intervention Type DRUG

Tacrolimus will be administered beginning on day +5

Mycophenolate Mofetil

Intervention Type DRUG

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

Rabbit ATG

Intervention Type BIOLOGICAL

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

Dexamethasone

Intervention Type DRUG

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

Bortezomib

Intervention Type DRUG

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

Rituximab

Intervention Type DRUG

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

Interventions

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Fludarabine

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

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide will be administered Post-Transplant

Intervention Type DRUG

Tacrolimus

Tacrolimus will be administered beginning on day +5

Intervention Type DRUG

Mycophenolate Mofetil

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

Intervention Type DRUG

Rabbit ATG

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

Intervention Type BIOLOGICAL

Dexamethasone

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

Intervention Type DRUG

Bortezomib

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

Intervention Type DRUG

Rituximab

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

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

2 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maria Cancio, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan Kettering at Basking Ridge (Consent only)

Basking Ridge, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Monmouth (Consent only)

Middletown, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Bergen (Consent only)

Montvale, New Jersey, United States

Site Status RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Consent only)

Commack, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Westchester (Consent only)

Harrison, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Nassau (All protocol activities)

Rockville Centre, New York, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Maria Cancio, MD

Role: CONTACT

212-639-2446

Jaap Jan Boelens, MD, PhD

Role: CONTACT

212-639-3643

Facility Contacts

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Maria Cancio, MD

Role: primary

212-639-2446

Maria Cancio, MD

Role: primary

212-639-2446

Maria Cancio, MD

Role: primary

212-639-2446

Maria Cancio, MD

Role: primary

212-639-2446

Maria Cancio, MD

Role: primary

212-639-2446

Maria Cancio, MD

Role: primary

212-639-2446

Related Links

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http://www.mskcc.org

Memorial Sloan Kettering Cancer Center

Other Identifiers

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23-009

Identifier Type: -

Identifier Source: org_study_id

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