Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease

NCT03121001 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 2016-1152
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a Phase II clinical trial. Patients will receive intensity modulated total body irradiation (TBI) at a dose of 3 Gy with standard fludarabine/ i.v. cyclophosphamide conditioning prior to human leukocyte antigen (HLA)-haploidentical hematopoietic stem cell transplant (HSCT). The primary objective of the study is to determine the engraftment at Day +60 following HLA-haploidentical hematopoietic stem cell transplant protocol using immunosuppressive agents and low-dose total body irradiation (TBI) for conditioning and post-transplant cyclophosphamide in patients with sickle cell disease.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Estimate the number of patients who engraft by Day +60

  Patients who achieve \< 5% peripheral blood donor chimerism by Day +30 and do not have a Day +60 measure will be regarded as failing to achieve full donor chimerism by Day +60; patients who achieve \> 5% donor chimerism by Day +30 but do not have a Day +60 measure will be considered nonevaluable for the primary endpoint.

  Up to Day +60

Secondary Outcomes (3)

• Disease free survival

  Up to Day +60

• Overall survival

  Up to Day +60

• Adverse Effects

  Up to Day +60

Study Arms (1)

Subject treatment

EXPERIMENTAL

Patients will receive the following conditioning regimen: ATG, fludarabine (6 days before stem cell infusion), cyclophosphamide, and total body irradiation. The stem cell product will be infused according to BMT unit policy. Patients will also receive GVHD prophylaxis which will consist of cyclophosphamide, sirolimus, and mycophenolate mofetil according to the protocol. Post-transplant evaluation will be done as per standard care with study data collected at days 30, 60, 100, 180, 365, and annually thereafter.

Drug: ATG; Drug: fludarabine; Drug: cyclophosphamide; Radiation: Total body irradiation; Procedure: Stem cell infusion; Drug: Sirolimus; Drug: mycophenolate mofetil

Interventions

ATG DRUG

0.5 mg/kg IV on day -9, and 2 mg/kg on days -8 and day -7

Also known as: Thymoglobulin®

Subject treatment

fludarabine DRUG

30 mg/m2 IVPB daily for day -6 (6 days before stem cell infusion) through day -2

Subject treatment

cyclophosphamide DRUG

14.5 mg/kg IV on days -6 and -5 and 50 mg/kg/d on days +3 and +4

Subject treatment

Total body irradiation RADIATION

3 Gy on day -1

Subject treatment

Stem cell infusion PROCEDURE

Stem cell product infused according to BMT unit policy on day 0.

Subject treatment

Sirolimus DRUG

loading dose of 15 mg followed by 5 mg per day on day +5

Subject treatment

mycophenolate mofetil DRUG

1 g every 8 h (until day 35) will be started on day 5

Subject treatment

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

Patient Eligibility: 1. Patients with sickle cell disease are eligible if they have any of the following complications: 1.1 Stroke or central nervous system event lasting longer than 24 hours 1.2 Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, hospital admissions, or home bedrest leading to absence from work or school. 1.3 Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits 1.4 Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events 1.5 Red-cell alloimmunization (≥ 2 antibodies) during long-term transfusion therapy 1.6 Bilateral proliferative retinopathy with major visual impairment in at least one eye 1.7 Osteonecrosis of 2 or more joints 1.8 Sickle cell nephropathy, defined by a GFR \< 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin \> 300 mg/g creatinine) 1.9 Pulmonary hypertension, defined by a mean pulmonary arterypressure \>25mmHg 2. Age 16-60 years 3. Karnofsky performance status of 60 or higher (Appendix A) 4. Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40% 5. Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration) 6. Estimated GFR ≥ 50mL/min/1.73m2 as calculated by the modified MDRD equation 7. ALT ≤ 3x upper limit of normal 8. HIV-negative 9. Patient is not pregnant 10. Patient is able and willing to sign informed consent 11. Patient does not have a fully HLA-matched sibling donor 12. Patient has an HLA-haploidentical relative Donor Eligibility Relatives (parents, offspring, siblings, aunts/uncles, cousins) will be tested by molecular typing of HLA class I (A, B, and C) and class II (DRB1) at low resolution. Only those that are an HLA-haploidentical match (≥ 4/8) will be considered as a potential donor. NOTE: If during testing, a fully HLA-matched sibling donor is found and is willing to donate his/her stem cells, the potential subject will not be eligible for this protocol. Donor consent will be obtained as per standard protocol of the bone marrow transplant unit.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

thymoglobulin; fludarabine; Cyclophosphamide; Whole-Body Irradiation; Sirolimus; Mycophenolic Acid

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; Radiotherapy; Therapeutics; Investigative Techniques; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Damiano Rondelli, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Damiano Rondelli, MD

CONTACT

312 413-3547; drond@uic.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Hematology

Study Record Dates

• First Submitted: April 14, 2017
• First Posted: April 19, 2017
• Study Start: March 20, 2017
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: January 26, 2026

Record last verified: 2026-01

Locations

US (1)