Sickle Cell DiseasePhase 1NCT03279094
Haploidentical Transplantation With Pre-Transplant Immunosuppressive Therapy for Patients With Sickle Cell Disease
A Phase 1 study testing Hematopoietic stem cell transplantation in people with Sickle Cell Disease, run by City of Hope Medical Center.
Trial summary
This is a study to evaluate the safety and toxicity of a treatment regimen consisting of 2 cycles of pre-transplant immunosuppressive therapy followed by myeloablative preparative regimen and allogeneic hematopoietic stem cell transplantation from a haploidentical donor in patients with sickle cell disease. Read more about this study
- Who is it for?
- Ages 1 year to 30 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Hematopoietic stem cell transplantation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 2 Feb 2018to 25 Jan 2027
- Phase
- Phase 1
- 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 1 year to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis: Patients with sickle cell anemia (Hgb SS or SB° Thalassemia) with baseline Hgb S more than 60%.
- Disease status:
- Significant neurologic event (stroke) or any neurological deficit lasting > 24 hours; or increased transcranial Doppler velocity (>200 m/s).
- History of one or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea).
- History of one or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea).
- Recurrent priapism requiring medical therapy.
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- Osteonecrosis of two or more joints despite the institution of supportive care measures.
- Prior treatment with regular RBC transfusion therapy, defined as receiving 8 or more transfusions per year for > 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome)
- Echocardiograph finding of tricuspid valve regurgitation jet (TRJ) velocity ≥ 2.5 m/sec.
- Ages 1 to 30.
- Child Bearing Potential- Transplantation could be teratogenic and/or lethal to the developing fetus. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately.
- Informed Consent/Assent: All subjects must have the ability to understand and the willingness to sign a written informed consent.
- The recipient must have a related donor who is genotypically haploidentical on HLA-A, B, C and DRB1 loci.
- No HLA matched sibling or 10/10 matched unrelated donor is available.
Who cannot join
- Any uncontrolled illness including ongoing or active bacterial, viral or fungal infection.
- Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any in the pre- or post-transplant regimen.
- Pregnant women are excluded from this study.
- Patients with any active malignancy are ineligible for this study, other than non-melanoma skin cancers.
- Medical problem or neurologic/psychiatric dysfunction which would impair patient ability to be compliant with the medical regimen and to tolerate transplantation or would prolong hematologic recovery which in the opinion of the principal investigator would place the recipient at unacceptable risk.
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- Prior autologous or allogeneic transplant.
- Fully HLA-matched related or unrelated donor is available to donate.
- Non-Compliance: Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
About this study
Official title: A Pilot Study of Pre-transplant Immunosuppressive Therapy for Haploidentical Transplants in Patients With Sickle Cell Disease
This is a study to evaluate the safety and toxicity of a treatment regimen consisting of 2 cycles of pre-transplant immunosuppressive therapy followed by myeloablative preparative regimen and allogeneic hematopoietic stem cell transplantation from a haploidentical donor in patients with sickle cell disease.
The overall goal of this study is to expand the donor pool for hematopoietic stem cell transplantation in sickle cell disease using haploidentical donors, and to develop a non-toxic, myeloablative regimen, with the goal of achieving a consistent donor chimerism utilizing pre-transplant immunosuppressive therapy.
Read the detailed description
All patients will receive an haploidentical hematopoietic stem cell transplant with the following conditioning and GvHD prevention:
Pre-transplant immunosuppressive therapy:
2 cycles of Fludarabine and Dexamethasone x 5 days each cycle
Conditioning regimen:
rATG daily x 3 days, Fludarabine daily x 6 days and Busulfan daily x 4 days
GVHD prophylaxis:
Cyclophosphamide day +3 and +4, Tacrolimus and Mycophenolate mofetil
- Conditions
- Sickle Cell Disease
- Being tested
- Hematopoietic stem cell transplantation
- Keywords
- Sickle Cell Disease, Hematopoietic stem cell transplantation, Haploidentical stem cell transplantation, Post-transplant Cytoxan
- 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.
Hematopoietic stem cell transplantationBiological
Haploidentical stem cell transplantation with pre-transplant immunosuppressive therapy
| Study group | Role | What they receive |
|---|---|---|
| Haploidentical stem cell transplantation | Experimental | Not described Receives: Biological: Hematopoietic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of unacceptable adverse events that are defined as any of the following events that occur from start of pre-transplant immunosuppressive therapy to the first 100 days post HCT:
- Rate of death of any causes
- Rate of study discontinuation or early withdrawal
- Rate of graft failure
- Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve <30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft.
- Rate of grade 4 non-hematological toxicities per NCI CTCAE v4.03 that last more than 21 days
Measured: 190 days
Secondary outcomes (12)
Time to donor neutrophil engraftment
Day of Neutrophil Engraftment: The first of three consecutive days on which the ANC is ≥0.5x109/L
Measured: 24 months
Time to donor platelets engraftment
Day of Platelet engraftment: The first documented day on which the platelet count is >20x109/L unsupported by platelet transfusions for 7 days
Measured: 24 months
Rate of graft failure
Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve <30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft.
Measured: 24 months
Incidence of acute GvHD (grade II - IV) during the first 100 days after transplantation
Measured: 100 days after transplantation
Incidence of chronic GvHD
Measured: 24 months
Overall survival rate
- Overall survival: the time from start of PTIS to death, or last follow-up, whichever comes first.
Measured: 24 months
Event-free survival rate
- Event-free survival: the time from start of PTIS to death, the unacceptable events, or last follow-up, whichever comes first.
Measured: 24 months
Disease free survival rate
- Disease free survival: the time from HCT to death, secondary graft failure, or last follow-up, whichever comes first.
Measured: 24 months
Immune reconstitution at day 100, 180 and 365
- Immune reconstitution: measurement of CD3, CD4, CD8, CD11b, CD14, CD56, CD20/19, FoxP3+ Treg, and memory subsets.
Measured: 24 months
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 from start of pre-transplant immunosuppressive therapy to 24 months post transplant
Measured: 24 months post-transplant
Percent of donor chimerism at 12 and 24 months after HCT
Measured: 12 and 24 months after HCT
Change From Baseline in Pain Scores using Numerical Rating Scale or Faces Pain Rating Scale at 100 days, 6 months and 12 months post-transplant
Measured: 100 days, 6 months and 12 months post-transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2017
- Study start2 Feb 2018 (estimated)
- Primary completion25 Jan 2027 (estimated)
- Study completion25 Jan 2027 (estimated)
Why it stopped: Closed to accrual - no accruals in CTMS
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 City of Hope Medical CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anna B. Pawlowska, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03279094
- Sponsor's protocol ID
- 17182
- Status last verified
- Oct 2026
- First submitted
- 6 Sep 2017
- Last updated
- 26 Oct 2026
- Results posted
- No
- 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 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of Pre-transplant Immunosuppressive Therapy for Haploidentical Transplants in Patients With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT03279094
- Acronym / sponsor ID
- 17182
- Conditions
- Sickle Cell Disease
- Keywords
- Sickle Cell Disease, Hematopoietic stem cell transplantation, Haploidentical stem cell transplantation, Post-transplant Cytoxan
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Closed to accrual - no accruals in CTMS
- Enrolment
- 0 participants (actual)
- Lead sponsor
- City of Hope Medical CenterUniversity, hospital or other
- Study start
- 2 Feb 2018 (estimated)
- Primary completion
- 25 Jan 2027 (estimated)
- Study completion
- 25 Jan 2027 (estimated)
- First posted
- 12 Sep 2017 (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.
This is a study to evaluate the safety and toxicity of a treatment regimen consisting of 2 cycles of pre-transplant immunosuppressive therapy followed by myeloablative preparative regimen and allogeneic hematopoietic stem cell transplantation from a haploidentical donor in patients with sickle cell disease.
The overall goal of this study is to expand the donor pool for hematopoietic stem cell transplantation in sickle cell disease using haploidentical donors, and to develop a non-toxic, myeloablative regimen, with the goal of achieving a consistent donor chimerism utilizing pre-transplant immunosuppressive therapy.
Detailed description
All patients will receive an haploidentical hematopoietic stem cell transplant with the following conditioning and GvHD prevention:
Pre-transplant immunosuppressive therapy:
2 cycles of Fludarabine and Dexamethasone x 5 days each cycle
Conditioning regimen:
rATG daily x 3 days, Fludarabine daily x 6 days and Busulfan daily x 4 days
GVHD prophylaxis:
Cyclophosphamide day +3 and +4, Tacrolimus and Mycophenolate mofetil
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Haploidentical stem cell transplantation | Experimental | Biological: Hematopoietic stem cell transplantation |
Who may qualify
- Ages
- 1 year to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Diagnosis: Patients with sickle cell anemia (Hgb SS or SB° Thalassemia) with baseline Hgb S more than 60%.
- Disease status:
- Significant neurologic event (stroke) or any neurological deficit lasting > 24 hours; or increased transcranial Doppler velocity (>200 m/s).
- History of one or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea).
- History of one or more severe vaso-occlusive pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea).
Key exclusion criteria (9 listed)
- Any uncontrolled illness including ongoing or active bacterial, viral or fungal infection.
- Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to any in the pre- or post-transplant regimen.
- Pregnant women are excluded from this study.
- Patients with any active malignancy are ineligible for this study, other than non-melanoma skin cancers.
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 |
|---|---|---|
| Hematopoietic stem cell transplantationHaploidentical stem cell transplantation with pre-transplant immunosuppressive therapy | Biological | Haploidentical stem cell transplantation |
Primary outcome
Rate of unacceptable adverse events that are defined as any of the following events that occur from start of pre-transplant immunosuppressive therapy to the first 100 days post HCT:
Time frame: 190 days
* Rate of death of any causes * Rate of study discontinuation or early withdrawal * Rate of graft failure • Primary graft failure is defined as failure to achieve a neutrophil count of 0.5 x 109/L before day +42 or mixed chimerism with failure to achieve <30% Hgb S on electrophoresis after day +180. Secondary graft failure is defined as recovery followed by a sustained loss of initial graft. * Rate of grade 4 non-hematological toxicities per NCI CTCAE v4.03 that last more than 21 days
12 secondary outcomes
Time to donor neutrophil engraftment
Time frame: 24 months
Time to donor platelets engraftment
Time frame: 24 months
Rate of graft failure
Time frame: 24 months
Incidence of acute GvHD (grade II - IV) during the first 100 days after transplantation
Time frame: 100 days after transplantation
Incidence of chronic GvHD
Time frame: 24 months
Overall survival rate
Time frame: 24 months
Event-free survival rate
Time frame: 24 months
Disease free survival rate
Time frame: 24 months
Immune reconstitution at day 100, 180 and 365
Time frame: 24 months
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 from start of pre-transplant immunosuppressive therapy to 24 months post transplant
Time frame: 24 months post-transplant
Percent of donor chimerism at 12 and 24 months after HCT
Time frame: 12 and 24 months after HCT
Change From Baseline in Pain Scores using Numerical Rating Scale or Faces Pain Rating Scale at 100 days, 6 months and 12 months post-transplant
Time frame: 100 days, 6 months and 12 months post-transplant
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 26 Oct 2026.
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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.
Anna B. Pawlowska, MD principal investigator
City of Hope Medical Center
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Hematopoietic stem cell transplantation in people with Sickle Cell Disease, run by City of Hope Medical Center.
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 14 inclusion and 9 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 26 Oct 2026. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Rate of unacceptable adverse events that are defined as any of the following events that occur from start of pre-transplant immunosuppressive therapy to the first 100 days post HCT: (time frame: 190 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 26 Oct 2026.