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)

NCT05736419 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 23-009
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 6

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment related mortality/TRM or primary graft failure

  The primary outcome is to estimate treatment-related mortality (TRM) or primary graft failure at 1 year post-HCT.

  1 year

Study Arms (1)

Participants with Sickle Cell Disease or β-Thalassemia

EXPERIMENTAL

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

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Biological: Rabbit ATG; Drug: Dexamethasone; Drug: Bortezomib; Drug: Rituximab

Interventions

Rituximab DRUG

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

Participants with Sickle Cell Disease or β-Thalassemia

Fludarabine DRUG

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

Participants with Sickle Cell Disease or β-Thalassemia

Cyclophosphamide DRUG

Cyclophosphamide will be administered Post-Transplant

Participants with Sickle Cell Disease or β-Thalassemia

Tacrolimus DRUG

Tacrolimus will be administered beginning on day +5

Participants with Sickle Cell Disease or β-Thalassemia

Mycophenolate Mofetil DRUG

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

Participants with Sickle Cell Disease or β-Thalassemia

Rabbit ATG BIOLOGICAL

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

Participants with Sickle Cell Disease or β-Thalassemia

Dexamethasone DRUG

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

Participants with Sickle Cell Disease or β-Thalassemia

Bortezomib DRUG

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

Participants with Sickle Cell Disease or β-Thalassemia

Eligibility Criteria

• Age: 2 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead

Study Sites (6)

Memorial Sloan Kettering at Basking Ridge (Consent only)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Consent only)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Consent only)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk - Commack (Consent only)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Consent only)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Nassau (All protocol activities)

Rockville Centre, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Anemia, Sickle Cell; beta-Thalassemia; Thalassemia

Interventions

fludarabine; Cyclophosphamide; Tacrolimus; Mycophenolic Acid; thymoglobulin; Dexamethasone; Bortezomib; Rituximab

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maria Cancio, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maria Cancio, MD

CONTACT

212-639-2446; canciom@mskcc.org

Jaap Jan Boelens, MD, PhD

CONTACT

212-639-3643; boelensj@mskcc.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 9, 2023
• First Posted: February 21, 2023
• Study Start: February 9, 2023
• Primary Completion (Estimated): February 9, 2027
• Study Completion (Estimated): February 9, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (6)