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)

June 2, 2026 updated by: Memorial Sloan Kettering Cancer Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Recruiting
        • Memorial Sloan Kettering at Basking Ridge (Consent Only)
        • Contact:
          • Maria Cancio, MD
          • Phone Number: 212-639-2446
      • Middletown, New Jersey, United States, 07748
        • Recruiting
        • Memorial Sloan Kettering Monmouth (Consent Only)
        • Contact:
          • Maria Cancio, MD
          • Phone Number: 212-639-2446
      • Montvale, New Jersey, United States, 07645
        • Recruiting
        • Memorial Sloan Kettering Bergen (Consent Only)
        • Contact:
          • Maria Cancio, MD
          • Phone Number: 212-639-2446
    • New York
      • Commack, New York, United States, 11725
        • Recruiting
        • Memorial Sloan Kettering Suffolk - Commack (Consent only)
        • Contact:
          • Maria Cancio, MD
          • Phone Number: 212-639-2446
      • Harrison, New York, United States, 10604
        • Recruiting
        • Memorial Sloan Kettering Westchester (Consent only)
        • Contact:
          • Maria Cancio, MD
          • Phone Number: 212-639-2446
      • Rockville Centre, New York, United States, 11553
        • Recruiting
        • Memorial Sloan Kettering Nassau (All Protocol Activities)
        • Contact:
          • Maria Cancio, MD
          • Phone Number: 212-639-2446

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

2 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Participants with Sickle Cell Disease or β-Thalassemia
Participants will have severe sickle cell disease or transfusion-dependent β-thalassemia.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants with treatment related mortality/TRM or primary graft failure
Time Frame: 1 year
The primary outcome is to estimate treatment-related mortality (TRM) or primary graft failure at 1 year post-HCT.
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Memorial Sloan Kettering Cancer Center

Investigators

  • Principal Investigator: Maria Cancio, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 9, 2023

Primary Completion (Estimated)

February 9, 2027

Study Completion (Estimated)

February 9, 2027

Study Registration Dates

First Submitted

February 9, 2023

First Submitted That Met QC Criteria

February 17, 2023

First Posted (Actual)

February 21, 2023

Study Record Updates

Last Update Posted (Actual)

June 3, 2026

Last Update Submitted That Met QC Criteria

June 2, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-009

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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