A Phase II Stratified Trial to Assess Haploidentical T-depleted Stem Cell Transplantation in Patients With Sickle Cell Disease With no Available Sibling Donor

Study point of contact

Katharina Kleinschmidt, MD
+49 (0)941 944-2101
[email protected]
Selim Corbacioglu, MD
+49 (0)941 944-2101
[email protected]


1 to 35 Years




Phase 2

Study type








About the study

HSCT is currently the only curative option for SCD but less than 20% of SCD patients have a
MD donor available. So far, all curative approaches beyond a MSD HSCT at young age are
non-satisfactory. With the lack of a suitable donor for the vast majority of patients, the
major question of this trial is, if a haploidentical αß/CD19+ T-cell depleted HSCT can be a
valid alternative to a MSD HSCT. The main challenge in non-malignant diseases is to offer a
safe and GvHD-free HSCT without rejection.

participation requirements

– Age 1yr to 35yrs

– Homozygous hemoglobin S disease or heterozygous hemoglobin SC or S 0/+

– Study specific consent given

– Preexisting severe or moderate SCD related complications:

– Clinically significant neurological event (stroke) or deficit

– Silent crisis, neurocognitive deficit

– Pathological angio-MRI with TOF Sequence

– TCD velocity >200 cm/s at 2 occasions >1 month apart

– More than 5 vaso-occlusive crises (VOC) in the past 1 year or more than 20 VOC in
a lifetime

– Two or more episodes of acute chest syndrome (ACS) in a lifetime or one episode
of ACS in the past 24 months

– Chronic transfusion requirement or more than 8 transfusions or one exchange
transfusion in a lifetime

– Transfusion-refractory allo-immunization

– More than five SCD-related hospitalizations in a lifetime

– Beginning pulmonary hypertension

– Osteonecrosis at more than 2 sites

– Beginning SCD Nephropathy

– Recurrent priapism (>2)

participation restrictions

– Karnofsky or Lansky Performance Score < 70% - Patients with donor-specific antibodies (DSA) against the potential stem cell donor by either - Cell-based crossmatched assays (Complement-dependent cytotoxicity; CDC) or - Flow cytometry crossmatch test or - Solid-phase immunoassays (SPI) or - Modified SPI such as C4d and C1q assays Whichever method the participating center is experienced in. - Patients with major AB0 incompatibility defined according to EBMT Handbook, Edition 2019 Tab 23.1.: ABO incompatibility Recipient Donor Major O A O B O AB A AB B AB - Cardiac function: - Ejection fraction at rest <45.0% on echocardiography or - Shortening fraction of ≥ 27.0% by echocardiogram or radionuclide scan (MUGA) - Patients with > grade II hypertension by Common Toxicity Criteria (CTC)

– Renal function:

– Estimated creatinine clearance (for patients > 12 years) greater than 50.0

– for pediatric patients (> 1 year to 12 years), GFR estimated by the updated
Schwartz formula ≥ 90.0 mL/min/1.73 m2. If < 90 mL/min/1.73 m2, renal function must be measured by 24-hour creatinine clearance or nuclear GFR and must be >
70.0 mL/min/1.73 m2 or

– Creatinine clearance below threshold defined for stem cell transplantation
according to local clinical standard

– Pulmonary function:

– DLCO >50% (adjusted for hemoglobin), and FVC and FEV1≥50%; children unable to
perform for PFTs, O2 saturation <92% on room air. - Liver function: - Total bilirubin > 2x the upper limit of normal (unless elevated bilirubin is
attributed to Gilbert’s Syndrome) and ALT/AST > 2.5x the upper limit of normal.

– Chronic active viral hepatitis

– Women who are pregnant (positive serum or urine βHCG) or breastfeeding. Note: Women of
childbearing potential must have a negative serum pregnancy test at study entry.

– Adults of reproductive potential not willing to use an effective method of birth
control during study treatment and for at least 12 months thereafter,

– History of uncontrolled autoimmune disease or on active treatment

– Patient unable to comply with the treatment protocol

– Prior autologous or allogeneic hematopoietic stem cell transplant

– Vaccination with a live virus vaccine during the trial

– HIV infection

– Patients with a history of psychiatric illness or a condition which could interfere
with their ability to understand the requirements of the study (this includes
alcoholism/drug addiction)

– Patients unwilling or unable to comply with the protocol or unable to give informed

– Concurrent severe or uncontrolled medical disease (e.g. uncontrolled diabetes,
congestive heart failure, myocardial infarction within 6 months prior to the study,
unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled
infection) which by assessment of the treating physician could compromise
participation in the study