Sickle Cell DiseasePhase 2NCT04817345
Peripheral Blood Stem Cell Collection From Patients With Sickle Cell Disease (SCD) Using Plerixafor
A Phase 2 study testing Plerixafor in people with Sickle Cell Disease, run by St. Jude Children's Research Hospital.
Trial summary
With recent advances in gene editing, gene therapy is becoming a viable curative treatment option for sickle cell disease. In order to do genetic manipulation, investigators need to collect hematopoietic stem cells from patients with sickle cell disease. Read more about this study
- Who is it for?
- Ages 10 to 25 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Plerixafor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Apr 2023to Apr 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 10 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with severe SCD who are 10-25 years old and are willing to donate autologous HSCs for advancing future gene therapy for SCD. Parents/legal guardians of participants must be able and willing to consent for their participation in this study. Severe SCD, for the purpose of this study, will be defined as patients who are receiving chronic transfusion therapy due to SCD related complications. The need for undergoing chronic transfusion therapy must be determined by the primary hematologist. Some patients may continue to receive hydroxyurea in addition to and simultaneously with blood transfusion therapy. Such patients are eligible for inclusion on the study if they hold hydroxyurea for at least 4 weeks. The ability to hold hydroxyurea (or not) with ongoing chronic transfusion therapy will be made by the primary hematologist as well. All genotypes of SCD will be eligible.
- Adequate renal function: serum/plasma creatinine < 1.5 mg/dL and creatinine clearance > 50 mL/min (as calculated by the Crockcroft-Gault formula).
- Adequate liver function: direct bilirubin < 2.5 times the upper limit of normal range, AST and ALT < 5 times the upper limit of normal range.
- Blood counts: WBC > 3,000/mm^3, granulocytes > 1,000/mm^3, hemoglobin > 7.0 g/dL, platelets > 150,000/mm^3.
- Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, have had a hysterectomy, be post-menopausal.
- Negative serologic tests for syphilis, hepatitis B and C, HIV, and HTLV-1/II.
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- Participants should either have a central line in place or be able to undergo apheresis without the necessity of the insertion of a central venous catheter
- Participants of childbearing potential should agree to use of an effective form of contraception during treatment and for at least 1 week after the last dose of plerixafor.
- ECOG performance status/Karnofsky score/Lansky score >80.
Who cannot join
- Pregnancy. Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, except those that have had a hysterectomy, or are post-menopausal.
- Active viral, bacterial, fungal, or parasitic infection.
- History of cancer, excluding squamous carcinoma of the skin and cervical carcinoma in situ.
- Active and painful splenomegaly or splenomegaly (size greater than upper limit of normal) or splenic sequestration determined by ultrasound.
- Previous history of splenomegaly or splenic sequestration, unless HbS level of <30% is documented within 48-72 hours of each plerixafor dose
- Allergy to plerixafor.
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- Patients receiving hydroxyurea will not be included in the study. However, they may be included if the primary hematologist determines that hydroxyurea can be safely discontinued for at least 4 weeks prior to the plerixafor administration and apheresis. Generally, patients receiving chronic transfusion therapy can safely discontinue hydroxyurea therapy as there is unlikely to be any added benefit, but this will be determined by the primary treating hematologist.
- Poor cardiac function, as defined by an ejection fraction < 40%.
- History of clinically proven pulmonary hypertension.
- Emergency room admission or hospitalization in the past 14 days prior to first dose of study drug.
- Major surgery in the past 30 days prior to first dose of study drug.
About this study
With recent advances in gene editing, gene therapy is becoming a viable curative treatment option for sickle cell disease. In order to do genetic manipulation, investigators need to collect hematopoietic stem cells from patients with sickle cell disease. In this study, investigators want to study the safety and feasibility of collecting peripheral blood stem cells from pediatric and young adult patients with sickle cell disease after administering plerixafor. Studying these peripheral blood stem cells will help in optimizing the yield of peripheral CD34+ cells from pediatric and young adult patients with sickle cell disease, which in turn will help to develop better gene therapies for these patients.
Primary Objectives
Read more
- Determine the safety profile associated with administration of plerixafor in pediatric and young adult patients with sickle cell disease (SCD).
- To estimate the number of CD34+ cells/kg of body weight that can be collected with peripheral apheresis after administration of plerixafor in pediatric and young adult patients with SCD.
Exploratory Objectives
- To describe the kinetics of CD34+ cell mobilization in peripheral blood after - + cells obtained from pediatric and young adult patients with SCD.
- To study the effect of hydroxyurea therapy on senescence in plerixafor-mobilized CD34+ cells obtained from pediatric and young adult patients with SCD.
Read the detailed description
Participants will be enrolled sequentially, and no two participants will undergo drug administration, mobilization or apheresis at the same time. A subsequent participant can only receive the study drug when the previous participant has been safely apheresed and discharged from the hospital. In the first stratum of the study only adult participants (18-25 years of age) will be enrolled. Once plerixafor and apheresis has been shown to be safe and acceptable in at least 5 adult participants, the study will enroll participants in the pediatric stratum. Pediatric stratum will not be activated until all the patients in the adult stratum have been evaluated and completed participation with acceptable results. In the pediatric stratum, older children (14 years old and above) will be enrolled before younger children (10-14 years old). After 10 participants, 14 years and older, have safely completed the study participation, younger children 10-14 years old will be allowed to participate.
Prophylactic red blood cell exchange or simple red cell transfusions will be given within 7 days prior to plerixafor administration to participants targeting HbS <30% to reduce the incidence of vaso-occlusive crisis and other events that may be associated with high hemoglobin S levels.Hydroxyurea treatment should be stopped 4 weeks before mobilization. Plerixafor administration and apheresis will be timed for participants already receiving chronic transfusion therapy such that the plerixafor administration and apheresis coincides with regularly timed transfusion.
Participants undergoing hematopoietic stem cell (HSC) mobilization will receive a daily-dose subcutaneous administration of plerixafor (Mozobil®) at 0.24 mg/kg on up to 2 consecutive days. Leukapheresis will start approximately 4 hours after each dose of plerixafor is given. This process lasts 4-10 hours.
Participants will be followed for 30 days after the last dose of plerixafor and then taken off study.
- Conditions
- Sickle Cell Disease
- Being tested
- Plerixafor
- Keywords
- Plerixafor, Leukapheresis, Mobilization, Stem Cells, Sickle Cell Disease
- 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.
PlerixaforDrug
Also called Mozobil ™
Subcutaneous
| Study group | Role | What they receive |
|---|---|---|
| Plerixafor | Experimental | Participants will receive a subcutaneous dose of 0.24 mg/kg of plerixafor once daily (Q24hr) x 2 days. Receives: Drug: Plerixafor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with sufficient collection of hematopoietic stem cells (HSCs) without serious adverse events.
Sufficient collection of HSCs from peripheral blood after plerixafor mobilization without serious adverse events (SAEs)
Measured: 2 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2021
- Study startApr 2023 (estimated)
- Primary completionApr 2023 (estimated)
- Study completionApr 2023 (estimated)
Why it stopped: The safety and efficacy of plerixafor in adult and pediatric SCD patients was an unknown when we started. A lot more data from therapeutic trials is available. We feel that recruiting patients without a therapeutic option isn't ethically justifiable.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research 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
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Doris Duke Charitable Foundation
- Responsible party
- Sponsor
- Investigators
- Akshay Sharma, MBBS, Principal investigator, St. Jude Children's Research HospitalMitch Weiss, MD, PhD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04817345
- Sponsor's protocol ID
- ASPIRES2
- Status last verified
- Apr 2023
- First submitted
- 23 Mar 2021
- Last updated
- 7 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Peripheral Blood Stem Cell Collection From Patients With Sickle Cell Disease (SCD) Using Plerixafor
- ClinicalTrials.gov ID
- NCT04817345
- Acronym / sponsor ID
- ASPIRES2
- Conditions
- Sickle Cell Disease
- Keywords
- Plerixafor, Leukapheresis, Mobilization, Stem Cells, Sickle Cell Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: The safety and efficacy of plerixafor in adult and pediatric SCD patients was an unknown when we started. A lot more data from therapeutic trials is available. We feel that recruiting patients without a therapeutic option isn't ethically justifiable.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- Doris Duke Charitable Foundation
- Study start
- Apr 2023 (estimated)
- Primary completion
- Apr 2023 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 26 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
With recent advances in gene editing, gene therapy is becoming a viable curative treatment option for sickle cell disease. In order to do genetic manipulation, investigators need to collect hematopoietic stem cells from patients with sickle cell disease. In this study, investigators want to study the safety and feasibility of collecting peripheral blood stem cells from pediatric and young adult patients with sickle cell disease after administering plerixafor. Studying these peripheral blood stem cells will help in optimizing the yield of peripheral CD34+ cells from pediatric and young adult patients with sickle cell disease, which in turn will help to develop better gene therapies for these patients.
Primary Objectives
- Determine the safety profile associated with administration of plerixafor in pediatric and young adult patients with sickle cell disease (SCD).
- To estimate the number of CD34+ cells/kg of body weight that can be collected with peripheral apheresis after administration of plerixafor in pediatric and young adult patients with SCD.
Exploratory Objectives
- To describe the kinetics of CD34+ cell mobilization in peripheral blood after - + cells obtained from pediatric and young adult patients with SCD.
- To study the effect of hydroxyurea therapy on senescence in plerixafor-mobilized CD34+ cells obtained from pediatric and young adult patients with SCD.
Detailed description
Participants will be enrolled sequentially, and no two participants will undergo drug administration, mobilization or apheresis at the same time. A subsequent participant can only receive the study drug when the previous participant has been safely apheresed and discharged from the hospital. In the first stratum of the study only adult participants (18-25 years of age) will be enrolled. Once plerixafor and apheresis has been shown to be safe and acceptable in at least 5 adult participants, the study will enroll participants in the pediatric stratum. Pediatric stratum will not be activated until all the patients in the adult stratum have been evaluated and completed participation with acceptable results. In the pediatric stratum, older children (14 years old and above) will be enrolled before younger children (10-14 years old). After 10 participants, 14 years and older, have safely completed the study participation, younger children 10-14 years old will be allowed to participate.
Prophylactic red blood cell exchange or simple red cell transfusions will be given within 7 days prior to plerixafor administration to participants targeting HbS <30% to reduce the incidence of vaso-occlusive crisis and other events that may be associated with high hemoglobin S levels.Hydroxyurea treatment should be stopped 4 weeks before mobilization. Plerixafor administration and apheresis will be timed for participants already receiving chronic transfusion therapy such that the plerixafor administration and apheresis coincides with regularly timed transfusion.
Participants undergoing hematopoietic stem cell (HSC) mobilization will receive a daily-dose subcutaneous administration of plerixafor (Mozobil®) at 0.24 mg/kg on up to 2 consecutive days. Leukapheresis will start approximately 4 hours after each dose of plerixafor is given. This process lasts 4-10 hours.
Participants will be followed for 30 days after the last dose of plerixafor and then taken off study.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Plerixafor | Experimental | Drug: PlerixaforParticipants will receive a subcutaneous dose of 0.24 mg/kg of plerixafor once daily (Q24hr) x 2 days. |
Who may qualify
- Ages
- 10 to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (9 listed)
- Patients with severe SCD who are 10-25 years old and are willing to donate autologous HSCs for advancing future gene therapy for SCD. Parents/legal guardians of participants must be able and willing to consent for their participation in this study. Severe SCD, for the purpose of this study, will be defined as patients who are receiving chronic transfusion therapy due to SCD related complications. The need for undergoing chronic transfusion therapy must be determined by the primary hematologist. Some patients may continue to receive hydroxyurea in addition to and simultaneously with blood transfusion therapy. Such patients are eligible for inclusion on the study if they hold hydroxyurea for at least 4 weeks. The ability to hold hydroxyurea (or not) with ongoing chronic transfusion therapy will be made by the primary hematologist as well. All genotypes of SCD will be eligible.
- Adequate renal function: serum/plasma creatinine < 1.5 mg/dL and creatinine clearance > 50 mL/min (as calculated by the Crockcroft-Gault formula).
- Adequate liver function: direct bilirubin < 2.5 times the upper limit of normal range, AST and ALT < 5 times the upper limit of normal range.
- Blood counts: WBC > 3,000/mm^3, granulocytes > 1,000/mm^3, hemoglobin > 7.0 g/dL, platelets > 150,000/mm^3.
- Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, have had a hysterectomy, be post-menopausal.
Key exclusion criteria (11 listed)
- Pregnancy. Female patients of childbearing age should have a negative serum pregnancy test within one week of beginning plerixafor administration, except those that have had a hysterectomy, or are post-menopausal.
- Active viral, bacterial, fungal, or parasitic infection.
- History of cancer, excluding squamous carcinoma of the skin and cervical carcinoma in situ.
- Active and painful splenomegaly or splenomegaly (size greater than upper limit of normal) or splenic sequestration determined by ultrasound.
- Previous history of splenomegaly or splenic sequestration, unless HbS level of <30% is documented within 48-72 hours of each plerixafor dose
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 |
|---|---|---|
| PlerixaforAlso: Mozobil ™Subcutaneous | Drug | Plerixafor |
Primary outcome
Number of participants with sufficient collection of hematopoietic stem cells (HSCs) without serious adverse events.
Time frame: 2 days
Sufficient collection of HSCs from peripheral blood after plerixafor mobilization without serious adverse events (SAEs)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant de-identified datasets containing the variables analyzed in the published article will be made available (related to the study primary or secondary objectives contained in the publication). Supporting documents such as the protocol, statistical analyses plan, and informed consent are available through the CTG website for the specific study. Data used to generate the published article will be made available at the time of article publication. Investigators who seek access to individual level de-identified data will contact the computing team in the Department of Biostatistics (ClinTrialDataRequest@stjude.org) who will respond to the data request.
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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.
Akshay Sharma, MBBS principal investigator
St. Jude Children's Research Hospital
Mitch Weiss, MD, PhD principal investigator
St. Jude Children's Research Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Plerixafor in people with Sickle Cell Disease, run by St. Jude Children's Research Hospital.
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 9 inclusion and 11 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: withdrawn, as of the sponsor's last update on 7 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of participants with sufficient collection of hematopoietic stem cells (HSCs) without serious adverse events. (time frame: 2 days). 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 7 Apr 2023.