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Sickle Cell DiseasePhase 2SUN-RAYNCT06358638

Sickle Cell Disease Transplant Using a Nonmyeloablative Approach for Patients With Anti-donor Red Cell Antibody

A Phase 2 study testing Daratumumab, Alemtuzumab and Sirolimus in people with Sickle Cell Disease, run by Children's National Research Institute at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell… Read more about this study

Who is it for?
Ages 2 to 25 years
Conditions the study is for
Sickle Cell Disease
What is being tested?
Daratumumab, Alemtuzumab and Sirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
12 participants
Where
1 siteUnited States
Study dates
3 Apr 2024to Sep 2054
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 2 to 25 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • General:
  • Patients with SCD age 2-24.99 years who have a healthy HLA-identical sibling donor with major ABO incompatibility OR patients with RBC alloantibodies against other donor RBC antigens.
  • Patients must have an absolute neutrophil count of 1 x 109/L and a platelet count of 100 x 109/L.
  • Lansky/Karnofsky score of, at least, 70.
  • Patients with genotypes hemoglobin SS and Sβ0 thalassemia must have at least one of the following:
  • History of an abnormal transcranial Doppler measurement defined as TCD velocity ≥200 cm/sec by the non-imaging technique measured at a minimum of two separate occasions.
Show all 22Show fewer
  • Progression of CNS vasculopathy on MRA determined to be secondary to SCD.
  • History of cerebral infarction on brain MRI (overt stroke, or silent stroke if ≥3 mm in one dimension, visible in two planes on fluid-attenuated inversion recovery T2-weighted images).
  • History of two or more episodes of Acute Chest Syndrome (ACS) in lifetime.
  • History of three or more SCD pain events requiring treatment with an opiate or IV pain medication in lifetime.
  • History of any hospitalization for a complication secondary to SCD (does NOT include empiric hospitalizations for fever only).
  • History of two or more episodes of priapism.
  • Administration of regular RBC transfusions (≥8 transfusions episodes in the previous 12 months).
  • At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.
  • Patients with all other sickle genotypes (e.g. hemoglobin SC, Sβ+ thalassemia, etc.) must have at least one of the following:
  • Clinically significant neurologic event (overt stroke).
  • History of two or more episodes of ACS in the 2-year period preceding enrollment.
  • History of three or more SCD pain events requiring treatment with an opiate or IV pain medication (inpatient or outpatient) in the 1-year period preceding enrollment.
  • History of any hospitalization for SCD pain or ACS while receiving hydroxyurea treatment.
  • History of two or more episodes of priapism (erection lasting ≥4 hours or requiring emergent medical care).
  • Administration of regular RBC transfusions (≥8 transfusions in the previous 12 months)
  • At least two episodes of splenic sequestration requiring red blood cell transfusion or splenectomy after at least one episode of splenic sequestration.

Who cannot join

  • Life expectancy less than 6 month
  • Pregnant or breastfeeding patients.
  • Infectious Disease: Uncontrolled bacterial, viral or fungal infections (undergoing appropriate treatment and with progression of clinical symptoms) within 1 month prior to conditioning. Patients with febrile illness or suspected minor infection should await clinical resolution prior to starting conditioning. Patients with confirmed seropositivity for HIV and patients with active or resolved Hepatitis B or C determined by serology and/or NAAT are excluded.
  • Liver: Direct (conjugated) bilirubin > 1.5 mg/dL. Transaminases >5x upper limit of normal for age.
  • Cardiac: Left ventricular shortening fraction <25% or ejection fraction <50% by ECHO. Uncontrolled cardiac arrhythmia.
  • Kidney: Estimated creatinine clearance less than 60 mL/min/1.73m2.
  • Pulmonary function: Diffusion capacity of carbon monoxide (DLCO) <35% (adjusted for hemoglobin). Baseline oxygen saturation <94% at rest or PaO2 <70. Known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification.
  • Heme: Available, medically suitable, and equivalent HLA-matched sibling donor, who does not have major ABO incompatibility or express RBC antigens against which the patient is alloimmunized.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting
  • Children's National Hospital

    Washington D.C., District of Columbia, 20010

    Maryanne Odinakachukwu, 202-476-2957, modinakach@childrensnational.org

    Robert Nickel

    Recruiting

Other trials in United States

About this study

Official title: Sickle Cell Disease Transplant Using a Nonmyeloablative Approach: Adding Daratumumab for Patients With Anti-donor Red Cell AntibodY

This multicenter prospective study seeks to determine if daratumumab given, prior to HLA-identical sibling donor transplantation using alemtuzumab, low dose total-body irradiation, and sirolimus, can prevent pure red blood cell aplasia with an acceptable safety profile in patients with anti-donor red blood cell antibodies, achieving an event-free survival similar to transplanted patients without such antibodies.

Read the detailed description

This study addresses an important question: Can daratumumab safely be administered prior to matched sibling donor (MSD) nonmyeloablative hematopoietic cell transplant (HCT) for SCD to avoid pure red blood cell aplasia in patients at risk of this complication? and thus achieve an event-free survival similar to patients without anti-donor red blood cell (RBC) antibodies?

Patients with anti-donor RBC antibodies, which includes patients with major ABO mismatch and other RBC alloantibodies against donor, have largely been excluded from the nonmyeloablative HCT approach given their risk of delayed donor RBC engraftment and/or hemolysis post-HCT. Exclusion of these patients limits access to less toxic curative therapies for this population at risk for toxicity due to their underlying multisystem disease. To address this need, we propose a multicenter clinical trial of Sickle cell disease Using a Nonmyeloablative approach: adding daratumumab for patients with anti-donor Red cell AntibodY (SUN-RAY). If successful, this trial will increase access to MSD nonmyeloablative HCT in SCD and will provide important safety and efficacy data for the use of daratumumab in the pre-HCT setting as well as in patients with SCD who have limited RBC donor options due to alloimmunization.

This is a phase 2 study given that the studied nonmyeloablative conditioning backbone (alemtuzumab, 300 cGY TBI, sirolimus) has been previously used effectively in both adults and children with SCD. Daratumumab will be added to this backbone with a washout period of 4 weeks prior to HCT infusion. Small case series have demonstrated that daratumumab is well tolerated either pre-HCT to treat patients with antibodies against mismatched donor HLA antigens, or post-HCT in patients with autoimmune cytopenias. The experience of the phase 2 clinical trial NCT03384654 studying daratumumab in pediatric acute lymphoblastic leukemia provides additional support for the safety and dosing of daratumumab for this study.

Being tested
Daratumumab, Alemtuzumab, Sirolimus, Total Body Irradiation
Keywords
Sickle Cell Disease, ABO Mismatch, SUN-RAY, Matched Sibling Donor (MSD)
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.

  • DaratumumabDrug

    Also called Darzalex

    Daratumumab is a cytotoxic monoclonal antibody (IgG1k) to CD38 and is commercially approved to treat multiple myeloma. CD38 is expressed on several types of blood cells including B-cells, antibody-secreting plasma blasts and plasma cells. As a result, it has been used to treat antibody-mediated diseases, including children with antibody-mediated cytopenias post-HCT.

  • AlemtuzumabDrug

    Also called Campath-1H

    Alemtuzumab is a humanized monoclonal antibody specific to lymphocyte antigens. It is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) that is directed against the 21-28 kD cell surface glycoprotein, CD52.

  • SirolimusDrug

    Also called Rapamune

    Sirolimus is an mTOR inhibitor immunosuppressant used to prevent organ transplant rejections as well as treat lymphangioleiomyomatosis and adults with perivascular epithelioid cell tumors.

  • Total Body IrradiationRadiation

    Also called TBI

    Total body irradiation is a form of radiotherapy used primarily as part of the preparative regimen for haematopoietic stem cell transplantation. The radiation is given in a low dose so that normal tissues can repair themselves.

Study groups in NCT06358638
Study groupRoleWhat they receive
Recipients with a major ABO incompatible donorExperimentalPatients in this cohort are treated pre-HCT with Daratumumab, intravenously, on days -49, -42, -35 and -28. The conditioning regimen will consist of alemtuzumab, given subcutaneously, daily for 5 days (days -7 to -3) and low dose total body irradiation (TBI) 300 cGY on day -2 with gonadal shielding. Sirolimus will be given as GVHD prophylaxis for the first year with weaning thereafter based on donor T-cell chimerism. G-CSF, at 5 mcg/kg/day, will be given post stem cell infusion until neutrophil engraftment is achieved.
Receives: Drug: Daratumumab; Drug: Alemtuzumab; Drug: Sirolimus; Radiation: Total Body Irradiation
Recipients with red cell alloantibodies (non-ABO) against donor antigensExperimentalPatients in this cohort are treated pre-HCT with Daratumumab, intravenously, on days -49, -42, -35 and -28. The conditioning regimen will consist of alemtuzumab, given subcutaneously, daily for 5 days (days -7 to -3) and low dose total body irradiation (TBI) 300 cGY on day -2 with gonadal shielding. Sirolimus will be given as GVHD prophylaxis for the first year with weaning thereafter based on donor T-cell chimerism. G-CSF, at 5 mcg/kg/day, will be given post stem cell infusion until neutrophil engraftment is achieved.
Receives: Drug: Daratumumab; Drug: Alemtuzumab; Drug: Sirolimus; Radiation: Total Body Irradiation

What is being measured

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

  1. To determine the event-free survival of children and adolescents with SCD undergoing nonmyeloablative HCT who received 4 doses of pre-HCT daratumumab for donor-directed red blood cell antibodies.

    Event-free survival rate at 1 year with events including death, graft failure (donor myeloid chimerism <10% or second HCT), grade II-IV GVHD, and serious pure red blood cell aplasia (persistent reticulocytopenia and need for red blood cell transfusion support after day +100).

    Measured: 1-year post-transplant

Secondary outcomes (2)
  1. To evaluate changes in antibodies to red blood cell antigens pre and post exposure to daratumumab and HCT.

    Antibodies titers against donor red blood cell antigens pre and post exposure to daratumumab. Anti-A and Anti-B titers, RBC alloantibody testing at baseline, day -7, day 0, day +30, and day +100.

    Measured: 100 days post-transplant

  2. To characterize the safety of adding pre-HCT daratumumab to the conditioning regimen, as defined by adverse events grade 3 or greater.

    Proportion of patients with infusion reactions and grade 3 adverse events related to daratumumab, and infections requiring treatment in the first year post-HCT, with comparison to historical controls on the SUN study.

    Measured: 1-year post-transplant

Timeline

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

  1. First posted10 Apr 2024
  2. Study start3 Apr 2024
  3. Primary completionSep 2044 (estimated)
  4. Study completionSep 2054 (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
Single group
Model description
Sickle cell patients, who have matched sibling donors with anti-donor RBC antibodies.
Masking
None (open label)
Enrolment
12 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06358638
Sponsor's protocol ID
STUDY00000859
Acronym
SUN-RAY
Status last verified
Sep 2025
First submitted
2 Apr 2024
Last updated
26 Sep 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daratumumab, Alemtuzumab and Sirolimus in people with Sickle Cell Disease, run by Children's National Research Institute 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 22 inclusion and 8 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: looking for participants now, as of the sponsor's last update on 26 Sep 2025. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Robert Nickel, MD (202-476-3122, rnickel@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

To determine the event-free survival of children and adolescents with SCD undergoing nonmyeloablative HCT who received 4 doses of pre-HCT daratumumab for donor-directed red blood cell antibodies. (time frame: 1-year 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 26 Sep 2025.

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