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

NCT ID: NCT03121001

Last Updated: 2024-11-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-20
• Study Completion Date: 2025-11-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Subject treatment

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.

Group Type: EXPERIMENTAL

ATG

Intervention Type: DRUG

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

fludarabine

Intervention Type: DRUG

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

cyclophosphamide

Intervention Type: DRUG

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

Total body irradiation

Intervention Type: RADIATION

3 Gy on day -1

Stem cell infusion

Intervention Type: PROCEDURE

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

Sirolimus

Intervention Type: DRUG

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

mycophenolate mofetil

Intervention Type: DRUG

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

Interventions

ATG

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

Intervention Type: DRUG

fludarabine

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

Intervention Type: DRUG

cyclophosphamide

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

Intervention Type: DRUG

Total body irradiation

3 Gy on day -1

Intervention Type: RADIATION

Stem cell infusion

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

Intervention Type: PROCEDURE

Sirolimus

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

Intervention Type: DRUG

mycophenolate mofetil

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

Intervention Type: DRUG

Other Intervention Names

Thymoglobulin®

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Illinois at Chicago

OTHER

Sponsor Role: lead

Responsible Party

Damiano Rondelli, MD

Professor, Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Damiano Rondelli, MD

Role: PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Locations

University of Illinois at Chicago

Chicago, Illinois, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Damiano Rondelli, MD

Role: CONTACT

drond@uic.edu

312 413-3547

Facility Contacts

Damiano Rondelli, MD

Role: primary

drond@uic.edu

312-413-3547

Other Identifiers

2016-1152

Identifier Type: -

Identifier Source: org_study_id