Sickle Cell DiseasePhase 2NCT01279616
A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease
A Phase 2 study testing Fludarabine monophosphate, Rituximab and Busulfan in people with Sickle Cell Disease, run by Nationwide Children's Hospital at 1 site in United States.
Trial summary
Majority of patients who are eligible for allogeneic HSCT for cure of severe sickle cell disease lack a matched family donor. This study aims for cure of sickle cell disease by performing unrelated donor (outside family) allogeneic HSCT. Donors or unrelated cord blood units will be selected from the NMDP database. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Fludarabine monophosphate, Rituximab and Busulfan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Jan 2015
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients must have sickle cell disease (genotype Hb SS or Sß° thalassemia), AND must have 1 or more of the following clinical complications related to Sickle cell disease:
- A clinically significant neurologic event (stroke) or any neurologic defect lasting >24 hours, that is accompanied by an infarct on cerebral MRI.
- Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar consolidation involving at least 1 complete lung segment associated with acute symptoms including fever, chest pain, tachypnea, wheezing or cough) despite adequate supportive care measures (example: asthma therapy, hydroxyurea).
- History of severe pain episodes defined as 3 or more severe pain events per year in the 2 years prior to enrollment despite adequate supportive care measures and hydroxyurea trial (i.e. Hydroxyurea non-responders). Pain may occur in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than vaso-occlusion mediated by sickle cell disease.
- Recurrent priapism.
- Osteo-necrosis of multiple joints
- Evidence of Pulmonary Hypertension as evidenced by Tricuspid Regurgitation jet velocity (TRV) > 2.5 m/s on Echocardiogram.
- Red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy.
Who cannot join
- Invasive bacterial, viral or fungal infections within 1 month prior to starting conditioning therapy.
- Female patients who are Pregnant (Beta HCG +) or breastfeeding.
- HIV positive patients.
- Patients with HLA-matched related family donors are not eligible for this study.
- Prior myeloablative allogeneic HCT.
- Patients on chronic transfusion therapy for ≥ 1 year with evidence of cirrhosis of liver on biopsy
- Any significant concurrent disease, illness, severe cognitive delay or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
About this study
Official title: A Pilot Study of an Immunosuppressive and Myeloablative Preparative Regimen for Allogeneic Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Severe Sickle Cell Disease
Majority of patients who are eligible for allogeneic HSCT for cure of severe sickle cell disease lack a matched family donor. This study aims for cure of sickle cell disease by performing unrelated donor (outside family) allogeneic HSCT. Donors or unrelated cord blood units will be selected from the NMDP database. It is designed to estimate the safety of a novel reduced toxicity, yet an immunosuppressive and myeloablative preparative regimen. This is meant for patients <21 years old who have severe complications from sickle cell and do not have matched sibling donors in the family to undergo stem cell transplant. Patients will undergo transplant using unrelated donor stem cells after receiving the protocol therapy. They will be followed for 1 year to monitor for engraftment of donor cells and complications like graft versus host disease (GVHD), infections and death.
Read the detailed description
The primary goal of this pilot study is to determine the safety and feasibility of the preparative regimen for HSCT using a novel reduced toxicity regimen for stem cell transplant with unrelated donors. Analysis will be geared to confirm if the study regimen, followed by an appropriately HLA-matched unrelated donor (MUD)or unrelated cord blood HSCT, can lead to durable donor engraftment with reasonable toxicity, inhibiting sickle erythropoiesis and limiting disease related organ toxicity in patients who are at high risk for morbidity and mortality associated with sickle cell disease (SCD).
- Conditions
- Sickle Cell Disease
- Being tested
- Fludarabine monophosphate, Rituximab, Busulfan, ATG, Cyclophosphamide
- Keywords
- sickle cell, stem cell transplant
- 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.
Fludarabine monophosphateDrug
180 mg/m2 over 6 days.
RituximabDrug
Also called Rituxan
375 mg/m2 on day -13 and day -3
BusulfanDrug
Also called busulfex
AUC 1000-1200 microM.mt
ATGDrug
Also called Thymoglobulin
2.5 mg/kg for 3 days
CyclophosphamideDrug
Also called Cytoxan
50 mg/kg on day +3
Also called MMF, Cell-cept.
15 mg/kg q 8 hours
TacrolimusDrug
Also called FK-506
0.03 mg/kg /d
| Study group | Role | What they receive |
|---|---|---|
| Hematopoietic Stem Cell Transplant | Experimental | Stem cell infusion on Day 0. Receives: Drug: Fludarabine monophosphate; Drug: Rituximab; Drug: Busulfan; Drug: ATG; Drug: Cyclophosphamide; Drug: Mycophenolate mofetil; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Event-free Survival
Event-free survival
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jan 2011 (estimated)
- Study startSep 2010
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: PI moving to a different institution.
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.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- 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
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sandeep Soni, MD, Study chair, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01279616
- Sponsor's protocol ID
- 09-00383
- Status last verified
- Apr 2019
- First submitted
- 18 Jan 2011
- Last updated
- 3 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of an Immunosuppressive and Myeloablative Preparative Regimen for Allogeneic Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Severe Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT01279616
- Acronym / sponsor ID
- 09-00383
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell, stem cell transplant
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI moving to a different institution.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- Sep 2010 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 19 Jan 2011 (estimated)
- Results
- Posted 3 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Majority of patients who are eligible for allogeneic HSCT for cure of severe sickle cell disease lack a matched family donor. This study aims for cure of sickle cell disease by performing unrelated donor (outside family) allogeneic HSCT. Donors or unrelated cord blood units will be selected from the NMDP database. It is designed to estimate the safety of a novel reduced toxicity, yet an immunosuppressive and myeloablative preparative regimen. This is meant for patients <21 years old who have severe complications from sickle cell and do not have matched sibling donors in the family to undergo stem cell transplant. Patients will undergo transplant using unrelated donor stem cells after receiving the protocol therapy. They will be followed for 1 year to monitor for engraftment of donor cells and complications like graft versus host disease (GVHD), infections and death.
Detailed description
The primary goal of this pilot study is to determine the safety and feasibility of the preparative regimen for HSCT using a novel reduced toxicity regimen for stem cell transplant with unrelated donors. Analysis will be geared to confirm if the study regimen, followed by an appropriately HLA-matched unrelated donor (MUD)or unrelated cord blood HSCT, can lead to durable donor engraftment with reasonable toxicity, inhibiting sickle erythropoiesis and limiting disease related organ toxicity in patients who are at high risk for morbidity and mortality associated with sickle cell disease (SCD).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Hematopoietic Stem Cell Transplant | Experimental | Drug: Fludarabine monophosphate, Drug: Rituximab, Drug: Busulfan, Drug: ATG, Drug: Cyclophosphamide, Drug: Mycophenolate mofetil, Drug: TacrolimusStem cell infusion on Day 0. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- Patients must have sickle cell disease (genotype Hb SS or Sß° thalassemia), AND must have 1 or more of the following clinical complications related to Sickle cell disease:
- A clinically significant neurologic event (stroke) or any neurologic defect lasting >24 hours, that is accompanied by an infarct on cerebral MRI.
- Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar consolidation involving at least 1 complete lung segment associated with acute symptoms including fever, chest pain, tachypnea, wheezing or cough) despite adequate supportive care measures (example: asthma therapy, hydroxyurea).
- History of severe pain episodes defined as 3 or more severe pain events per year in the 2 years prior to enrollment despite adequate supportive care measures and hydroxyurea trial (i.e. Hydroxyurea non-responders). Pain may occur in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than vaso-occlusion mediated by sickle cell disease.
- Recurrent priapism.
Key exclusion criteria (7 listed)
- Invasive bacterial, viral or fungal infections within 1 month prior to starting conditioning therapy.
- Female patients who are Pregnant (Beta HCG +) or breastfeeding.
- HIV positive patients.
- Patients with HLA-matched related family donors are not eligible for this study.
- Prior myeloablative allogeneic HCT.
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 |
|---|---|---|
| Fludarabine monophosphate180 mg/m2 over 6 days. | Drug | Hematopoietic Stem Cell Transplant |
| RituximabAlso: Rituxan375 mg/m2 on day -13 and day -3 | Drug | Hematopoietic Stem Cell Transplant |
| BusulfanAlso: busulfexAUC 1000-1200 microM.mt | Drug | Hematopoietic Stem Cell Transplant |
| ATGAlso: Thymoglobulin2.5 mg/kg for 3 days | Drug | Hematopoietic Stem Cell Transplant |
| CyclophosphamideAlso: Cytoxan50 mg/kg on day +3 | Drug | Hematopoietic Stem Cell Transplant |
| Mycophenolate mofetilAlso: MMF, Cell-cept.15 mg/kg q 8 hours | Drug | Hematopoietic Stem Cell Transplant |
| TacrolimusAlso: FK-5060.03 mg/kg /d | Drug | Hematopoietic Stem Cell Transplant |
Primary outcome
Event-free Survival
Time frame: 1 year
Event-free survival
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 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.
Sandeep Soni, MD study chair
Nationwide Children's Hospital
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 Fludarabine monophosphate, Rituximab and Busulfan in people with Sickle Cell Disease, run by Nationwide Children's Hospital 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?
The sponsor lists 8 inclusion and 7 exclusion criteria. 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 3 Apr 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 3 Apr 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?
Event-free Survival (time frame: 1 year). 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 3 Apr 2019.