Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This is a clinical trial that will compare survival and sickle related outcomes in
adolescents and young adults with severe sickle cell disease after bone marrow
transplantation and standard of care. The primary outcome is 2-year overall survival.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Leukemia/heme
Enrollment Eligibility
Inclusion Criteria:
1. Age ≥ 15 and < 41 years
2. Severe sickle cell disease [Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin
SBeta thalassemia (Hb Sβ) genotype] with at least 1 of the following manifestations
(a-e):
1. Clinically significant neurologic event (stroke) or any neurological deficit
lasting > 24 hours;
2. History of two 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);
3. An average of three or more pain crises per year in the 2-year period preceding
enrollment (required intravenous pain management in the outpatient or inpatient
hospital setting). Clinical documentation of pain management in the inpatient or
outpatient setting is required.
4. Administration of regular RBC transfusion therapy, defined as receiving 8 or more
transfusion events per year (in the 12 months before enrollment) to prevent
vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest
syndrome)
5. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥
2.7 m/sec.
6. Ongoing high impact chronic pain on a majority of days per month for ≥ 6 months
as defined as ONE or more of the following: Chronic pain without contributory SCD
complications, OR Mixed pain type in which chronic pain is occurring at site(s)
(arms, back, chest, or abdominal pain) unrelated to any sites associated with
Contributory SCD complications (e.g. leg ulcers and/or avascular necrosis).
i. High impact chronic pain is identified as those reporting "severe interference"
with life activities OR "usually or always" experiencing a limitation of their life or
work activities including household chores. (See guidelines for identifying HICP in
the BMT CTN 1503 Manual of Procedures) ii. Contributory SCD complications are defined
as clinical signs (e.g. presence of leg ulcers) or clinical assessments (e.g. imaging
confirmation of splenic infarct or avascular necrosis). Chronic pain attributed solely
to contributory SCD complications is excluded.
3. Adequate physical function as measured by all of the following:
1. Karnofsky/Lansky performance score ≥ 60
2. Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV
shortening fraction > 26% by cardiac echocardiogram or by Multi Gated Acquisition
Scan (MUGA).
3. Pulmonary function:
a. Pulse oximetry with a baseline O2 saturation of ≥ 85% b. Diffusing capacity of the
lung for carbon monoxide (DLCO) > 40% (corrected for hemoglobin) d. Renal function:
Serum creatinine ≤ 1.5 x the upper limit of normal for age as per local laboratory and
24 hour urine creatinine clearance >70 mL/min; or GFR > 70 mL/min/1.73 m2 by
radionuclide Glomerular Filtration Rate (GFR).
e. Hepatic function:
1. Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per
local laboratory. Participants are not excluded if the serum conjugated (direct)
bilirubin is >2x the upper limit of normal for age as per local laboratory and:
There is evidence of a hyperhemolytic reaction after a recent RBC transfusion, OR
there is evidence of moderate direct hyperbilirubinemia defined as direct serum
bilirubin < 5 times ULN and not caused by underlying hepatic diseasePatients
2. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times
upper limit of normal as per local laboratory.
Additional inclusion required for donor arm participants to proceed with transplant
1. Liver MRI (≤ 90 days prior to initiation of transplant conditioning) to document
hepatic iron content is required for participants who are currently receiving ≥8
packed red blood cell transfusions for ≥1 year or have received ≥20 packed red blood
cell transfusions (cumulative). Participants who have hepatic iron content ≥7 mg Fe/ g
liver dry weight by liver MRI must have a liver biopsy and histological
examination/documentation of the absence of cirrhosis, bridging fibrosis and active
hepatitis (≤ 90 days prior to initiation of transplant conditioning).
2. Lack of clinical or radiologic evidence of a recent neurologic event (such as stroke
or transient ischemic attack) by Cerebral MRI/MRA within 30 days prior to initiating
transplant conditioning. Subjects with clinical or radiologic evidence of a recent
neurologic event will be deferred for ≥ 6 months with repeat cerebral MRI/MRA to
ensure stabilization of the neurologic event prior to proceeding to transplantation
3. Documentation of participant's willingness to use approved contraception method until
discontinuation of all immunosuppressive medications is to be documented in the
medical record corresponding with the consent conference.
Exclusion Criteria:
1. HLA typing with a donor search prior to referral (consultation with HCT physician).
1. If a subject has had HLA typing and a related donor search that did not identify
a suitably matched relative (i.e., sibling) at any time, and also did not have an
unrelated donor search, the patient will be considered eligible.
2. If a subject has had HLA typing and a related donor search that did not identify
a suitably matched relative (i.e., sibling) at any time and had an unrelated
donor search that did not identify a suitably matched unrelated donor ≥ 1 year
prior to enrollment, the patient will be considered eligible.
3. If a subject has had HLA typing with no related donor search and had an unrelated
donor search that did not identify a suitably matched unrelated donor ≥ 1 year
prior to enrollment, the patient will be considered eligible.
4. Subjects with a known HLA-identical sibling or HLA-matched unrelated donor are
excluded
2. Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
3. Seropositivity for HIV.
4. Previous HCT or solid organ transplant.
5. Participation in a clinical trial in which the patient received an investigational
drug or device must be discontinued at enrollment.
6. A history of substance abuse as defined by version IV of the Diagnostic & Statistical
Manual of Mental Disorders (DSM IV).
7. Demonstrated lack of compliance with prior medical care as determined by referring
physician.
8. Pregnant or breast feeding females.
9. Inability to receive HCT due to alloimmunization, defined as the inability to receive
packed red blood cell (pRBC) transfusion therapy.