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Sickle Cell DiseasePhase 2NCT02105766

Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-thalassemia in People With Higher Risk of Transplant Failure

A Phase 2 study testing Alemtuzumab, Sirolimus and Cyclophosphamide in people with Sickle Cell Disease and Thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Background: Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want to test a variation of transplant that uses low dose radiation and a combination of immunosuppressive drugs. They want to know if it helps a body to better accept donor stem cells. Read more about this study

Who is it for?
Ages 4 to 80 yearsHealthy volunteers can take part
What is being tested?
Alemtuzumab, Sirolimus and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
1 siteUnited States
Study dates
21 Apr 2014to 31 Dec 2027
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 4 to 80 years
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

Who may be able to join

  • -6/6 HLA matched family donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Matched related donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of eligibility and suitability for clinical donation. Note that participation in this study is offered to all matched related donors, but is not required for a donor to make a stem cell donation, so it is possible that not all related donors will enroll onto this study.

Who cannot join

  • -None

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Nonmyeloablative Peripheral Blood Mobilized Hematopoietic Precursor Cell Transplantation for Sickle Cell Disease and Beta-Thalassemia in Individuals With Higher Risk of Transplant Failure

Background:

  • Some sickle cell disease or beta-thalassemia can be cured with transplant. Researchers want to test a variation of transplant that uses low dose radiation and a combination of immunosuppressive drugs. They want to know if it helps a body to better accept donor stem cells.
Read more

Objectives:

  • To see if low dose radiation (300 rads), oral cyclophosphamide, pentostatin, and sirolimus help a body to better accept donor stem cells.

Eligibility:

  • People 4 and older with beta-thalassemia or sickle cell disease that can be cured with transplant, and their donors.

Design:

  • Participants and donors will be screened with medical history, physical exam, blood test, tissue and blood typing, and bone marrow sampling. They will visit a social worker.
  • Donors:
  • may receive an intravenous (IV) tube in their groin vein.
  • will receive a drug injection daily for 5 or 6 days to move the blood stem cells from the bone marrow into general blood circulation.
  • will undergo apheresis: an IV is put into a vein in each arm. Blood is taken from one arm, a machine removes the white blood cells that contain blood stem cells, and the rest is returned through the other arm.
  • Participants:
  • may undergo red cell exchange procedure.
  • will remain in the hospital for about 30 days.
  • will receive a large IV line that can stay in their body from transplant through recovery.
  • will receive a dose of radiation, and transplant related drugs by mouth or IV.
  • will receive blood stem cells over 8 hours by IV.
  • will take neuropsychological tests and may complete questionnaires throughout the transplant process.
  • must stay near NIH for 4 months. They will visit the outpatient clinic weekly.
Read the detailed description

Our ongoing nonmyeloablative allogeneic peripheral blood stem cell (PBSC) transplant protocol (03-H-0170) for patients with severe sickle cell disease (SCD) and B-thalassemia from HLA-matched family donors has excellent results thus far. Our long term leukocyte engraftment rate is 85-90% with the same disease-free survival. None of the engrafted patients had acute sickle-related events, significant toxicity associated with the conditioning regimen, or any evidence of graft versus host disease (GVHD).

While these results rival the transplant outcomes from low risk transplant patients with B-thalassemia, there are areas for improvement. The first is the 10-15% graft rejection rate, where a majority of these individuals were male donor and female recipient pairs. Another limitation is the significant delay in donor red cell engraftment in one recipient who had pre-existing allo-antibody to donor red cells from previous transfusions. Also we have excluded another group of individuals with preformed antibodies, recipients having major ABO incompatibility to the donors.

To overcome these limitations (and reduce the transplant failure rate) in this new protocol, we will continue our nonmyeloablative approach in the patients with SCD and B-thalassemia with HLA-matched family donors, but using an increased intensity regimen in a subset considered at high risk for transplant failure. This modified regimen consists of pentostatin and oral cyclophosphamide, which we hypothesize will reduce both the T cells that mediate leukocyte rejection and the B/plasma cells that produce anti-donor erythrocyte antibodies. The main transplant backbone will remain as alemtuzumab, low dose total body irradiation of 300 cGy, and sirolimus; the transplant graft will remain as unmanipulated G-CSF mobilized, T-cell replete, PBSC product for hematopoietic and lymphoid reconstitution.

The primary endpoint of this study is the percentage/number of patients who have sustained donor type hemoglobin at 1 year post transplant for male donors - female recipients. The primary endpoint for those with pre-existing antibodies is the presence of donor red cells with reticulocytes greater than or equal to 30 k/uL at 2 years post-transplant. Other endpoints include the toxicity of the pentostatin-cyclophosphamide regimen, the degree of donor-host chimerism necessary for long-term graft survival and disease amelioration, incidence of acute and chronic GVHD, incidence of graft rejection, transplant-related morbidity, as well as disease-free and overall survival. Since SCD and B-thalassemia are non-malignant disorders of red cells, severe GVHD, lack of donor erythrocyte (prolonged donor red cell aplasia), or graft rejection is collectively considered transplant failure.

Being tested
Alemtuzumab, Sirolimus, Cyclophosphamide, Pentostatin, Radiotherapy
Keywords
Sickle Cell Disease, Allogeneic Hematopoietic Stem Cell Transplant, Pentostatin (Nipent), Cyclophosphamide, Alemtuzumab (Campath)
Medical subject headings
Anemia, Sickle Cell, Thalassemia, Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlemtuzumabDrug

    Also called Campath

    Immunosuppressant

  • SirolimusDrug

    Also called Rapamune

    Immunosuppressant

  • CyclophosphamideDrug

    Also called Cytoxan

    Immunosuppressant

  • PentostatinDrug

    Also called Deoxycoformycin

    Immunosuppressant

  • RadiotherapyProcedure or surgery

    Immunosuppressant and myelosuppressant

  • FilgrastimDrug

    Also called Neupogen

    mobilize peripheral blood stem cells for apheresis collection

Study groups in NCT02105766
Study groupRoleWhat they receive
Female participants with SCD or Beta-thalassemia receiving stem cell transplant with male donorExperimentalFemale participants with Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant with male donor. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.
Receives: Drug: Alemtuzumab; Drug: Sirolimus; Drug: Cyclophosphamide; Drug: Pentostatin; Procedure: Radiotherapy
Participants with pre-existing antibodies and SCD or Beta-thalassemia receiving stem cell transplantExperimentalParticipants with pre-existing antibodies and Sickle Cell Disease (SCD) or Beta-thalassemia receiving stem cell transplant. Pentostatin given on days -21, -17, -13, -9 and oral cyclophosphamide from days -21 to -8, with the intention to be administered in the outpatient setting. Alemtuzumab on days 7 to 3, and 300 cGy TBI on day 2. Sirolimus started at a loading dose of 5mg PO every 4 hours for three doses on day -1 and adjusted to maintain trough levels between 10-15 ng/mL. The PBSC graft targeted to deliver .10 x 106 CD34+ cells/kg (minimum .5 x 106) and infused on day 0.
Receives: Drug: Alemtuzumab; Drug: Sirolimus; Drug: Cyclophosphamide; Drug: Pentostatin; Procedure: Radiotherapy
Human Leukocyte Antigens (HLA) Matched Related Stem Cell DonorOtherParticipants received filgrastim to mobilize peripheral blood stem cells for apheresis collection. Collected stem cells of donor will then be infused to HLA matched sibling.
Receives: Drug: Filgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant

    Number of patients who have sustained donor type hemoglobin at one year post transplant. Sustained donor type hemoglobin is based on hemoglobin electrophoresis for patients with SCD and transfusion independence for patients with beta-thalassemia

    Measured: 1 year

  2. Number of Participants With Donor Red Cells at 2 Years Post Stem Cell Transplant

    Number of participants with donor red cells at 2 years post stem cell transplant. Number of participants with donor red cells is detected by hemoglobin electrophoresis or donor type red cell antigen, and reticulocyte count ≥30 k/uL at 2 years post-transplant.

    Measured: 2 years

Secondary outcomes (13)

  1. Mean CD34+ Cell Dose

    Mean CD34+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected

    Measured: Day 0 up to Day 1

  2. Mean CD3+ Cell Dose

    Mean CD3+ cell dose, filgrastim mobilized peripheral blood hematopoietic cells, unselected

    Measured: Day 0 up to Day 1

  3. Median Percent of Donor T-cells and Myeloid Chimerism

    Median Percent of donor T-cells and myeloid chimerism. Leukocytes are selected by magnetic beads for CD3 (T-cells) and CD14/15 (myeloid cells), then microsatellite PCR analyses are performed to obtain donor chimerism percent.

    Measured: day 30, day 60 , day 100, 1 year and 2 year

  4. Number of Participants Who Developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV

    Number of participants who developed Acute Graft vs Host Disease (GVHD) Grades I, II, III, IV as defined by CIMBTR criteria for Organ Stages of Acute GVHD.

    Grades are defined as:

    Grade I: Skin = Maculopapular rash< 25% of body surface area (BSA); Liver = Total Bilirubin 2-3 mg/dL; Lower GI = stool output/day is 500-999 mL/day.

    Grade II: Skin = rash on 25-50 percent body surface area; Liver = Total Bilirubin 3.1-6.0 mg/dL; Lower GI = Diarrhea 1001-1500 mL/day.

    Grade III: Skin = Rash on >50% of body surface; Liver = Total Bilirubin 6.1 - 15.0 mg/dL; Lower GI = Diarrhea > 1500 mL/day.

    Grade IV: Skin = Generalized erythroderma plus bullous formation; Liver = Total Bilirubin >15 mg/dL; Lower GI = Severe abdominal pain with or without ileus.

    Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

    Measured: Up to Day 100

  5. Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD)

    Number of Participants Who Developed Moderate or Severe Chronic Graft vs Host Disease (GVHD) up to 5 years.

    Moderate chronic GVHD involves EITHER 3 organs/sites with no clinically significant functional impairment OR a less than or equal to 1 organ/site with clinically significant functional impairment, but no major disability. Severe GVHD is associated with a major disability caused by chronic GVHD.

    Measured: Day 100 up to 2 years

  6. Number of Participants That Experienced Graft Failure or Graft Rejection, or Red Cell Aplasia at 2 Years After Transplant

    Number of participants that experienced graft failure or graft rejection, or red cell aplasia at 2 years after transplant. Graft failure or graft rejection is defined as <5% donor cells in both CD3 and myeloid chimerism. Red cell aplasia is defined as reticulocyte <30 k/uL and requiring red cell transfusions.

    Measured: Up to 2 years

  7. Number of Participants That Experienced Regimen Failure

    Number of Participants That Experienced Regimen Failure. Regimen failure is defined as those participants that experienced grade 3 or higher acute GVHD, moderate/severe chronic GVHD, graft failure/rejection, or red cell aplasia. Together any one of these count toward the combined endpoint of regimen failure.

    Measured: Up to 2 years

  8. Number of Participants That Experienced Transplant-related Mortality

    Number of participants that experienced transplant-related mortality. Transplant-related mortality is defined as death that is at least possibly related to the transplant (GVHD, toxicity, infection, other causes).

    Measured: Up to 2 years

  9. Percentage of Participant With Disease-free Survival Following Stem Cell Transplant

    Percentage of participant with disease-free survival following stem cell transplant. Disease-free survival is defined as alive and free acute complications related to sickle cell disease.

    Measured: Up to 2 years

  10. Percentage of Participant Overall Survival Following Stem Cell Transplant

    Percentage of Participant Overall Survival up to year 2 following stem cell transplant. Overall survival is defined as being alive following stem cell transplant.

    Measured: Up to 2 years

  11. Median Day to Neutrophil Recovery

    Median Day to Neutrophil recovery. Neutrophil recovery is defined as the first of three consecutive days of neutrophil count >0.5 x 10^9 cells/uL.

    Measured: Up to Day 100

  12. Median Days to Platelet Recovery

    Median Days to Platelet Recovery. Platelet recovery is defined as count >50 cells/uL and 7 days from the last platelet transfusion.

    Measured: Up to Day 120

  13. Median Days to Red Cell Recovery

    Median Days to Red Cell Recovery. Red cell recovery defined as days to recovery of reticulocyte count .30 k/uL, detection of donor red cells, transfusion independence.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Apr 2014 (estimated)
  2. Study start21 Apr 2014
  3. Primary completion31 Dec 2023
  4. Study completion31 Dec 2027 (estimated)

Resources

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
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02105766
Sponsor's protocol ID
140077
Other IDs
14-H-0077
Status last verified
Aug 2026
First submitted
1 Apr 2014
Last updated
18 Aug 2026
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD that underlie results in a publication

Publications

  • Kern KC, Inam Z, Hsieh MM, Tisdale JF, Fitzhugh CD, Limerick EM, Gebremeskel ASK, White T, Jordan LC, Lynch JK. Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease. Neurology. 2026 Jun 9;106(11):e218050. doi: 10.1212/WNL.0000000000218050. Epub 2026 May 14.

    PubMed 42133908

  • Inam Z, Jeffries N, Link M, Coles W, Pollack P, Luckett C, Phang O, Harvey E, Martin T, Farrey T, Tisdale JF, Hsieh MM. Two Nonmyeloablative HLA-Matched Related Donor Allogeneic Hematopoietic Cell Transplantation Regimens in Patients with Severe Sickle Cell Disease. Transplant Cell Ther. 2025 May;31(5):305-318. doi: 10.1016/j.jtct.2025.02.021. Epub 2025 Feb 24.

    PubMed 40010689

  • Leonard A, Furstenau D, Abraham A, Darbari DS, Nickel RS, Limerick E, Fitzhugh C, Hsieh M, Tisdale JF. Reduction in vaso-occlusive events following stem cell transplantation in patients with sickle cell disease. Blood Adv. 2023 Jan 24;7(2):227-234. doi: 10.1182/bloodadvances.2022008137.

    PubMed 36240296

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alemtuzumab, Sirolimus and Cyclophosphamide in people with Sickle Cell Disease and Thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) 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 1 inclusion and 1 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: under way, not looking for participants, as of the sponsor's last update on 18 Aug 2026. 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 29 Nov 2024). 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?

Number of Patients Who Have Sustained Donor Type Hemoglobin at One Year Post Transplant (time frame: 1 year). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02105766, which also lists 3 linked publications.

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 18 Aug 2026.

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