Ph I/II Study of Allogeneic SCT for Clinically Aggressive Sickle Cell Disease (SCD)
Phase I/II Study of Allogeneic Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease (SCD)
1 other identifier
interventional
45
1 country
1
Brief Summary
The investigators propose to determine the engraftment and transplant related morbidity and mortality after a non-myeloablative allogeneic hematopoietic stem cell transplant protocol using immune- suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy in patients with aggressive sickle cell disease who are not candidates for or experienced complications from hydroxyurea therapy. Fully HLA matched siblings will be used as donors for hematopoietic stem cells to reduce the risk of morbidity and mortality in this cohort of patients.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Nov 2011
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 11, 2011
CompletedFirst Submitted
Initial submission to the registry
November 23, 2011
CompletedFirst Posted
Study publicly available on registry
December 26, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 23, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
October 1, 2029
April 11, 2025
April 1, 2025
16.9 years
November 23, 2011
April 8, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To determine the engraftment after non-myeloablative HSC transplant
Up to 30 days post-transplant.
Secondary Outcomes (4)
To assess the frequency of acute and chronic complications of sickle cell disease
Up to 100 days post-transplant.
To evaluate the immune reconstitution after transplant.
Up to 12 months after transplant.
To determine the transplant related morbidity and mortality.
Up to 365 days post-transplant.
To determine the long-term engraftment after non-myeloablative HSC transplant
Up to 10 years post-transplant.
Other Outcomes (1)
To determine whether ocular findings from sickle cell disease are reversible in patients undergoing stem cell transplantation to treat their sickle cell disease.
Up to 5 years post-transplant
Study Arms (1)
Allogeneic Non-Myeloablative Stem Cell Transplantation
EXPERIMENTALThe transplant regimen will consist of alemtuzumab 1mg/kg divided over five days, 300 cGy TBI, followed by sirolimus dosed for a target serum trough level of 10- 15 ng/mL.
Interventions
Alemtuzumab-based non-myeloablative allogeneic hematopoietic stem cell transplantation using immune-suppressive agents and low-dose total body irradiation (TBI) without standard chemotherapy. Transplant regimen Day -7 to -3: Alemtuzumab (1mg/kg, total dose) divided over the 5 days, IVPB over 2 hours daily Day -3 until 100% chimerism obtained: Sirolimus dosed for target trough level of 10-15 ng/mL Day -2: Total body irradiation with 300cGy Day 0: Stem cell infusion
In this protocol, patients will be given alemtuzumab 1mg/kg divided equally over five days with the maximum dose of 20mg per day.
On day -1, patients will receive a loading dose of 12 mg followed by 4 mg per day. Subsequent dosing will be based on clinical toxicity, GVHD concurrent medications, medical conditions, prior drug levels, drug-drug interactions, and blood levels with target of 3 to 12 ng/mL.
Eligibility Criteria
You may qualify if:
- Patients with sickle cell disease, subtype Hgb SS, SC, or SB disease who are on chronic transfusion therapy for a prior stroke or those patients who were intolerant of hydroxyurea therapy or were being treated with hydroxyurea therapy and were complicated by at least one of the following:
- Stroke or central nervous system event lasting longer than 24 hours
- Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year severe enough to interfere with the patient's normal daily function or require medical attention in the clinic, emergency room, acute care center, or hospital
- Recurrent episodes of priapism, defined as ≥ 2 per year requiring emergency room visits
- Acute chest syndrome with recurrent hospitalizations, defined as ≥ 2 lifetime events
- Red-cell alloimmunization (≥ 2 antibodies) during longterm transfusion therapy
- Bilateral proliferative retinopathy with major visual impairment in at least one eye
- Osteonecrosis of 2 or more joints
- Sickle cell nephropathy
- Stage I or II sickle lung disease
- Symptoms of pulmonary hypertension and mean pulmonary artery pressure \> 25mmHg
- Age 16-60 years
- Karnofsky performance status of 70 or higher
- Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%
- Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50%
- +8 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Illinois at Chicago
Chicago, Illinois, 60612, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Damiano Rondelli, MD
University of Illinois at Chicago
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
November 23, 2011
First Posted
December 26, 2011
Study Start
November 11, 2011
Primary Completion (Estimated)
September 23, 2028
Study Completion (Estimated)
October 1, 2029
Last Updated
April 11, 2025
Record last verified: 2025-04