Status:
TERMINATED
Stem Cell Transplant in Patients With Severe Sickle Cell Disease
Lead Sponsor:
Kathleen Dorritie
Conditions:
Sickle Cell Disease
Eligibility:
All Genders
18+ years
Phase:
EARLY_PHASE1
Brief Summary
This is a prospective pilot study of matched-related donor allogeneic stem cell transplantation in adults with severe sickle cell disease using a matched-sibling PBSC graft with a non-myeloablative co...
Detailed Description
Stem cell transplantation recipients will be given Alemtuzumab, which is a non-myeloablative pre-transplant conditioning regimen. This non-myeloablative therapy uses doses of chemotherapy and radiatio...
Eligibility Criteria
Inclusion
- Patient selection
- Age \> 18 years
- Patients with Hb SS, Hb SC, Hb Sβ0 genotype
- Presence of at least 1 of the following manifestations:
- History of clinically significant neurologic event defined as stroke or any neurological deficit lasting \> 24 hours.
- 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
- Three or more pain crises per year in the 2-year period preceding referral (required intravenous pain management in the outpatient or inpatient hospital setting).
- This may include painful episodes related to priapism, osteonecrosis or any sickle-related complication.
- An echocardiographic finding of the tricuspid valve regurgitant jet (TRJ) velocity ≥ 2.7 m/sec.
- History of osteonecrosis or avascular necrosis of ≥ 2 joints
- Administration of 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)
- History of RBC allo-immunization but without detectable allo-antibodies.
- Evidence of sickle hepatopathy or iron overload in patients who received ≥ 8 packed RBC transfusions for ≥ 1 year or have received ≥ 20 cumulative packed RBC transfusions. These patients will undergo MRI of the liver to estimate liver iron content.
- Patients with hepatic iron content of ≤ 7 mg Fe/ gm of liver will be included ii. Patients with hepatic iron content of ≥ 7 mg Fe/ gm of liver will undergo biopsy to look for absence of histological findings suggestive of cirrhosis, fibrosis and active hepatitis
- h. Sickle nephropathy defined as Cr ≥ 1.5 times the ULN or biopsy proven i.Reversible SCD complication not ameliorated by hydroxyurea: i.Two or more vaso-occlusive crises requiring hospitalizations ii. Any episode of ACS while on hydroxyurea
- Adequate physical function as measured by all of the following:
- Karnofsky performance score \> or equal to 70
- Cardiac function: Left ventricular ejection fraction (LVEF) \> 40%; or LV shortening fraction \> 26% by cardiac echocardiogram or by MUGA scan.
- Pulmonary function: Pulse oximetry with a baseline O2 saturation of \> 85%, DLCO \> 40% (corrected for hemoglobin).
- 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/1.73 m2; or GFR \> 70 mL/min/1.73 m2 by radionuclide GFR unless reason for transplant is sickle nephropathy
- Hepatic function:
- i. Serum conjugated (direct) bilirubin \< 2x upper limit of normal for age as per local laboratory; ii. ALT and AST \< 5 times upper limit of normal. iii. Patients with hyperbilirubinemia because of hyper hemolysis, or who experience a sudden, profound change in the serum hemoglobin after a RBC transfusion are not excluded.
- The HLA matched related donor must be willing to donate and must meet our institutional guidelines to donate peripheral blood stem cells
- Absence of donor specific HLA antibodies.
- Absence of clinical or radiographic evidence of neurologic event within 6 months prior to proceeding with transplantation.
- Cerebral MRI/MRA within 6 months prior to initiation of transplant conditioning.
- If patient has a neurologic event such as stroke or transient ischemic attack during recruitment process, patient will be deferred for 6 months before reconsideration.
- Donor selection
- Siblings who are ≥18 years and capable and willing to donate PBSC
- Sibling donors are HLA-matched. HLA-A, B, C, and DRB1 match based on high-resolution typing
- All sibling donors MUST meet institutional criteria for donation.
- Donors with sickle cell trait (Hb AS) are permitted.
- Donors with ABO minor incompatibility are permitted
Exclusion
- Patient selection
- Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
- Seropositivity for HIV.
- Previous stem cell transplantation.
- Participation in a clinical trial in which the patient received an investigational drug or device
- A history of substance abuse as defined by version IV of the Diagnostic \& Statistical Manual of Mental Disorders (DSM IV).
- Demonstrated lack of compliance with prior medical care as determined by referring physician.
- Pregnant or breast-feeding females.
- Unwillingness to use approved contraception method from time of conditioning regimen and 4 months after discontinuation of all immunosuppressive medications.
- Donor selection A. Inclusion Criteria
- Siblings who are ≥18 years and capable and willing to donate PBSC
- Sibling donors are HLA-matched. HLA-A, B, C, and DRB1 match based on high-resolution typing
- All sibling donors MUST meet institutional criteria for donation.
- Donors with sickle cell trait (Hb AS) are permitted.
- Donors with ABO minor incompatibility are permitted
- B. Exclusion Criteria
- Donors with hemoglobinopathies: Hb SS, Hb SC, Hb Sβ0 and all other unstable hemoglobins
- Presence of anti-donor HLA antibodies in the recipient
- Donors with major ABO incompatibility are permitted
- Donors who are HIV-1, HIV-2, HTLV-1, HTLV-2 seropositive or with active hepatitis B or hepatitis C virus infection
Key Trial Info
Start Date :
March 29 2018
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
May 15 2022
Estimated Enrollment :
1 Patients enrolled
Trial Details
Trial ID
NCT03421756
Start Date
March 29 2018
End Date
May 15 2022
Last Update
June 28 2022
Active Locations (1)
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1
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, United States, 15232