Sickle Cell DiseasePhase 2SCD-HaploNCT02013375
SCD-Haplo: Phase II Study of HLA-Haploidentical SCT for Aggressive SCD
A Phase 2 study testing Haploidentical Transplant, Alemtuzumab and Total Body Irradiation in people with Sickle Cell Disease, run by Damiano Rondelli, MD at 1 site in United States.
Trial summary
Related donor stem cell transplantation using the alemtuzumab/ TBI platform has been shown to be a safe strategy to cure severe sickle cell disease. However, due to a lack of suitable donors, many patients cannot benefit from this strategy. Alternative donor sources are desperately needed to fill this gap. Read more about this study
- Who is it for?
- Ages 16 to 60 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Haploidentical Transplant, Alemtuzumab and Total Body Irradiation
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Apr 2014to 7 Sep 2018
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Patient Eligibility:
- Patients with sickle cell disease are eligible if they have any of the following complications:
- Stroke or central nervous system event lasting longer than 24 hours
- Frequent vaso-occlusive pain episodes, defined as ≥ 3 per year requiring emergency room, acute care center, or hospital admissions.
- 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 long-term transfusion therapy
- Bilateral proliferative retinopathy with major visual impairment in at least one eye
- Osteonecrosis of 2 or more joints
- Sickle cell nephropathy, defined by a GFR < 90mL/min/1.73m2 or the presence of macroalbuminuria (urine albumin > 300 mg/g creatinine)
- Pulmonary hypertension, defined by a mean pulmonary artery pressure > 25mmHg
- Age 16-60 years
- Karnofsky performance status of 60 or higher
- Adequate cardiac function, defined as left ventricular ejection fraction ≥ 40%
- Adequate pulmonary function, defined as diffusion lung capacity of carbon monoxide ≥ 50% predicted (after adjustment for hemoglobin concentration)
- Estimated GFR ≥ 50mL/min as calculated by the modified MDRD equation
- ALT ≤ 3x upper limit of normal
- HIV-negative
- Patient is pregnant
- Patient is able and willing to sign informed consent
- Patient has an HLA-haploidentical relative
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Illinois Cancer Center
Chicago, Illinois, 60612
About this study
Official title: SCD-Haplo: A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
Related donor stem cell transplantation using the alemtuzumab/ TBI platform has been shown to be a safe strategy to cure severe sickle cell disease. However, due to a lack of suitable donors, many patients cannot benefit from this strategy. Alternative donor sources are desperately needed to fill this gap. Nearly all patients will have a haploidentical family member who would be able to donate. The use of post transplantation cyclophosphamide has greatly improved the outcome of haploidentical stem cell transplantation. The investigators propose to combine this with alemtuzumab/TBI conditioning.
Read the detailed description
Sickle cell anemia is an inherited form of anemia, a condition in which there aren't enough healthy red blood cells to carry adequate oxygen throughout the body. These patients are at increased risk of death, stroke, frequent pain crises, acute chest syndrome as well as chronic conditions including: lung damage, retinopathy, kidney damage, leg ulcers, and pulmonary hypertension.
There's no cure for most people with sickle cell anemia. However, treatments can relieve pain and help prevent co-morbid conditions associated with sickle cell anemia. Hydroxyurea is the only FDA approved drug to help alleviate symptoms associated with sickle cell disease. The mortality rate is still high in patients using hydroxyurea and a significant percentage of patients still have aggressive disease despite the hydroxyurea treatment. Hydroxyurea therapy also does not seem to prevent the development of many of the complications of sickle cell disease such as pulmonary hypertension.
Historically, stem cell transplantation in sickle cell disease was mainly done in the pediatric population. The options were more limited for adults with sickle cell disease with aggressive disease despite hydroxyurea. Most rely on chronic red blood cell transfusions which carry significant risks of infection, iron overload, and alloimmunization. Alloimmunization refers to the production of antibodies which occurs in up to 50% of patients with sickle cell disease who are on chronic transfusion therapy making further transfusions difficult with a high potential for hemolytic transfusion reactions.
Recently the use of a non-myeloablative stem cell transplantation regimen (relying on immunotherapy instead of chemotherapy) for sickle cell disease in adults showed 88% engraftment rates (30 out of 34 patients) with no GVHD and 0% mortality. However, these transplants used only fully HLA-matched siblings, which are unavailable to all but approximately 14-28% of patients who could benefit from such a transplant at UIC.
A recent study at Johns Hopkins carried out a similar haploidentical (half matched) transplant with 14 sickle cell patients who lacked fully HLA-matched donors. Approximately two years following transplant, 57% of patients successfully engrafted (8 or 14 patients). There were no deaths and only one episode of acute GVHD of the skin which resolved without therapy.
The investigators plan to offer stem cell transplantation to sickle cell patients with aggressive disease who only have a partially matched HLA sibling donor. Haploidentical transplants are considered only for patients with no other standard options available who would normally be treated with supportive (palliative) care or given the option to participate in a clinical trial. Donors who are HLA-haploidentical will be the source of hematopoietic stem cells. Potential donors can include any relative (e.g. parents, offspring, siblings, cousins, aunts/uncles, grandparents).
The related donor stem cell transplantation using the alemtuzumab/TBI platform has been shown to be a safe strategy to cure severe sickle cell disease. However, due to a lack of suitable donors, many patients cannot benefit from this strategy. Alternative donor sources are desperately needed to fill this gap. Nearly all patients will have a haploidentical family member who would be able to donate. The use of post transplantation cyclophosphamide has greatly improved the outcome of haploidentical stem cell transplantation. The investigators propose to combine this with alemtuzumab/TBI conditioning.
The investigational component of this study is the combination of the Alemtuzumab (immunotherapy) and Total Body Irradiation conditioning regimen and the HLA Haploidentical Transplant with post-transplant Cyclophosphamide. Investigators plan to study the engraftment rates (transplant success rates) at Day 60 in sickle cell patients undergoing an HLA haploidentical stem cell transplant with post transplant high dose cyclophosphamide.
- Conditions
- Sickle Cell Disease
- Being tested
- Haploidentical Transplant, Alemtuzumab, Total Body Irradiation, Cyclophosphamide, Sirolimus
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Haploidentical TransplantProcedure or surgery
Also called Mismatched allogeneic bone marrow transplant
All subjects will undergo pre-conditioning treatment with alemtuzumab (0.3 mg/kg Day -5, Day -4, Day -3) and total body irradiation (300cGy), followed by stem cell transplant, and post-transplant treatment with cyclophosphamide (50mg/kg/day) and sirolimus (target trough level of 10-15ng/mL).
AlemtuzumabDrug
Also called Campath®
On Day -7, the first test dose of alemtuzumab (0.03 mg/kg) will be administered and on Day -6, the second test dose of alemtuzumab (0.1 mg/kg) will be administered. Alemtuzumab (0.3 mg/kg) will be infused daily on Day -5, -4, and -3.
Total Body IrradiationRadiation
A 300cGy dose of TBI will be administered in a single fraction on Day -2.
CyclophosphamideDrug
Also called Cytoxan®
Cyclophosphamide (50 mg/kg IBW) IV, over approximately 1-2 hours, is given on Day 3 post-transplantation (ideally between 60 and 72 hours after marrow infusion) and on Day 4 (approximately 24 hours after Day 3 cyclophosphamide).
SirolimusDrug
Also called Rapamune®
Sirolimus will be started on Day +5 (at least 24 hours after the completion of the cyclophosphamide infusion). The starting dose will be 12mg followed by 4mg PO daily. Doses will be adjusted to achieve a whole blood trough level of 4 - 12ng/mL.
| Study group | Role | What they receive |
|---|---|---|
| Haploidentical Transplant | Experimental | All subjects will undergo pre-conditioning treatment with alemtuzumab (0.3 mg/kg Day -5, Day -4, Day -3) and total body irradiation (300cGy), followed by stem cell transplant, and post-transplant treatment with cyclophosphamide (50mg/kg/day) and sirolimus (target trough level of 10-15ng/mL). Receives: Procedure: Haploidentical Transplant; Drug: Alemtuzumab; Radiation: Total Body Irradiation; Drug: Cyclophosphamide; Drug: Sirolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Engraftment Rate
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.
Measured: Up to Day 60 post-transplant.
Secondary outcomes (3)
Acute & Chronic Complications
To assess the frequency of acute and chronic complications of sickle cell disease during and after HLA-haploidentical hematopoietic stem cell transplantation with this protocol. The acute complications include vaso-occlusive pain episodes, acute chest syndrome, stroke, and priapism. The chronic complications include nephropathy, retinopathy, osteonecrosis, pulmonary artery pressures, cardiomyopathy, and chronic lung disease.
Measured: Up to one year post-transplant
Overall & Disease-Free Survival
To determine the overall and disease-free survival of patients with sickle cell disease receiving HLA-haploidentical hematopoietic stem cell transplantation with this protocol.
Measured: Up to one year post-transplant.
Morbidity & Mortality
To determine the incidence of acute and chronic graft-versus-host disease, the incidence of infectious complications, and the transplant related mortality in sickle cell disease patients after HLA-haploidentical hematopoietic stem cell transplantation with this protocol.
Measured: Up to one year post-transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2013 (estimated)
- Study start10 Apr 2014
- Primary completion31 May 2014
- Study completion7 Sep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Damiano Rondelli, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Damiano Rondelli, MD, University of Illinois Chicago
- Investigators
- Damiano Rondelli, MD, Principal investigator, University of Illinois Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02013375
- Sponsor's protocol ID
- 2013-0849
- Acronym
- SCD-Haplo
- Status last verified
- Aug 2019
- First submitted
- 11 Dec 2013
- Last updated
- 28 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- SCD-Haplo: A Phase II Study of HLA-Haploidentical Stem Cell Transplantation to Treat Clinically Aggressive Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT02013375
- Acronym / sponsor ID
- SCD-Haplo / 2013-0849
- Conditions
- Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Damiano Rondelli, MDUniversity, hospital or other
- Study start
- 10 Apr 2014 (actual)
- Primary completion
- 31 May 2014 (actual)
- Study completion
- 7 Sep 2018 (actual)
- First posted
- 17 Dec 2013 (estimated)
- Results
- Posted 28 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Related donor stem cell transplantation using the alemtuzumab/ TBI platform has been shown to be a safe strategy to cure severe sickle cell disease. However, due to a lack of suitable donors, many patients cannot benefit from this strategy. Alternative donor sources are desperately needed to fill this gap. Nearly all patients will have a haploidentical family member who would be able to donate. The use of post transplantation cyclophosphamide has greatly improved the outcome of haploidentical stem cell transplantation. The investigators propose to combine this with alemtuzumab/TBI conditioning.
Detailed description
Sickle cell anemia is an inherited form of anemia, a condition in which there aren't enough healthy red blood cells to carry adequate oxygen throughout the body. These patients are at increased risk of death, stroke, frequent pain crises, acute chest syndrome as well as chronic conditions including: lung damage, retinopathy, kidney damage, leg ulcers, and pulmonary hypertension.
There's no cure for most people with sickle cell anemia. However, treatments can relieve pain and help prevent co-morbid conditions associated with sickle cell anemia. Hydroxyurea is the only FDA approved drug to help alleviate symptoms associated with sickle cell disease. The mortality rate is still high in patients using hydroxyurea and a significant percentage of patients still have aggressive disease despite the hydroxyurea treatment. Hydroxyurea therapy also does not seem to prevent the development of many of the complications of sickle cell disease such as pulmonary hypertension.
Historically, stem cell transplantation in sickle cell disease was mainly done in the pediatric population. The options were more limited for adults with sickle cell disease with aggressive disease despite hydroxyurea. Most rely on chronic red blood cell transfusions which carry significant risks of infection, iron overload, and alloimmunization. Alloimmunization refers to the production of antibodies which occurs in up to 50% of patients with sickle cell disease who are on chronic transfusion therapy making further transfusions difficult with a high potential for hemolytic transfusion reactions.
Recently the use of a non-myeloablative stem cell transplantation regimen (relying on immunotherapy instead of chemotherapy) for sickle cell disease in adults showed 88% engraftment rates (30 out of 34 patients) with no GVHD and 0% mortality. However, these transplants used only fully HLA-matched siblings, which are unavailable to all but approximately 14-28% of patients who could benefit from such a transplant at UIC.
A recent study at Johns Hopkins carried out a similar haploidentical (half matched) transplant with 14 sickle cell patients who lacked fully HLA-matched donors. Approximately two years following transplant, 57% of patients successfully engrafted (8 or 14 patients). There were no deaths and only one episode of acute GVHD of the skin which resolved without therapy.
The investigators plan to offer stem cell transplantation to sickle cell patients with aggressive disease who only have a partially matched HLA sibling donor. Haploidentical transplants are considered only for patients with no other standard options available who would normally be treated with supportive (palliative) care or given the option to participate in a clinical trial. Donors who are HLA-haploidentical will be the source of hematopoietic stem cells. Potential donors can include any relative (e.g. parents, offspring, siblings, cousins, aunts/uncles, grandparents).
The related donor stem cell transplantation using the alemtuzumab/TBI platform has been shown to be a safe strategy to cure severe sickle cell disease. However, due to a lack of suitable donors, many patients cannot benefit from this strategy. Alternative donor sources are desperately needed to fill this gap. Nearly all patients will have a haploidentical family member who would be able to donate. The use of post transplantation cyclophosphamide has greatly improved the outcome of haploidentical stem cell transplantation. The investigators propose to combine this with alemtuzumab/TBI conditioning.
The investigational component of this study is the combination of the Alemtuzumab (immunotherapy) and Total Body Irradiation conditioning regimen and the HLA Haploidentical Transplant with post-transplant Cyclophosphamide. Investigators plan to study the engraftment rates (transplant success rates) at Day 60 in sickle cell patients undergoing an HLA haploidentical stem cell transplant with post transplant high dose cyclophosphamide.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Haploidentical Transplant | Experimental | Procedure: Haploidentical Transplant, Drug: Alemtuzumab, Radiation: Total Body Irradiation, Drug: Cyclophosphamide, Drug: SirolimusAll subjects will undergo pre-conditioning treatment with alemtuzumab (0.3 mg/kg Day -5, Day -4, Day -3) and total body irradiation (300cGy), followed by stem cell transplant, and post-transplant treatment with cyclophosphamide (50mg/kg/day) and sirolimus (target trough level of 10-15ng/mL). |
Who may qualify
- Ages
- 16 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Haploidentical TransplantAlso: Mismatched allogeneic bone marrow transplantAll subjects will undergo pre-conditioning treatment with alemtuzumab (0.3 mg/kg Day -5, Day -4, Day -3) and total body irradiation (300cGy), followed by stem cell transplant, and post-transplant treatment with cyclophosphamide (50mg/kg/day) and sirolimus (target trough level of 10-15ng/mL). | Procedure or surgery | Haploidentical Transplant |
| AlemtuzumabAlso: Campath®On Day -7, the first test dose of alemtuzumab (0.03 mg/kg) will be administered and on Day -6, the second test dose of alemtuzumab (0.1 mg/kg) will be administered. Alemtuzumab (0.3 mg/kg) will be infused daily on Day -5, -4, and -3. | Drug | Haploidentical Transplant |
| Total Body IrradiationA 300cGy dose of TBI will be administered in a single fraction on Day -2. | Radiation | Haploidentical Transplant |
| CyclophosphamideAlso: Cytoxan®Cyclophosphamide (50 mg/kg IBW) IV, over approximately 1-2 hours, is given on Day 3 post-transplantation (ideally between 60 and 72 hours after marrow infusion) and on Day 4 (approximately 24 hours after Day 3 cyclophosphamide). | Drug | Haploidentical Transplant |
| SirolimusAlso: Rapamune®Sirolimus will be started on Day +5 (at least 24 hours after the completion of the cyclophosphamide infusion). The starting dose will be 12mg followed by 4mg PO daily. Doses will be adjusted to achieve a whole blood trough level of 4 - 12ng/mL. | Drug | Haploidentical Transplant |
Primary outcome
Engraftment Rate
Time frame: Up to Day 60 post-transplant.
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.
3 secondary outcomes
Acute & Chronic Complications
Time frame: Up to one year post-transplant
Overall & Disease-Free Survival
Time frame: Up to one year post-transplant.
Morbidity & Mortality
Time frame: Up to one year post-transplant.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Damiano Rondelli, MD principal investigator
University of Illinois Chicago
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Haploidentical Transplant, Alemtuzumab and Total Body Irradiation in people with Sickle Cell Disease, run by Damiano Rondelli, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Engraftment Rate (time frame: Up to Day 60 post-transplant.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2019.