A Study to Compare Bone Marrow Transplantation to Standard Care in Adolescents and Young Adults with Severe Sickle Cell Disease

Investigator: Lazaros Lekakis

Institutional Protocol #: 20160027

National Clinical Trials Identifier: NCT02766465

Funding Agency/Sponsor: Blood and Marrow Transplant

Division: Cancer Center

Therapeutic Area: Leukemia, Lymphoma, and Myeloma

Phase: Phase II

Enrolling Sites: University of Miami Hospital, University of Miami Hospital & Clinics, University of Miami Medical Group

Enrolling Since: 9/1/2017


Purpose/Abstract:


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.




Eligibility Criteria:


Inclusion Criteria:

1. Age 15.00 - 40.99 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. 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)

4. 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)

5. An echocardiographic finding of tricuspid valve regurgitant jet (TRJ) velocity ≥
2.7 m/sec.

3. Adequate physical function as measured by all of the following:

1. Karnofsky/Lansky performance score > or equal to 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: Pulse oximetry with a baseline O2 saturation of ≥ 85% and
Diffusing capacity of the lung for carbon monoxide (DLCO) > 40% (corrected for
hemoglobin)

4. 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).

5. Hepatic function: Serum conjugated (direct) bilirubin < 2x upper limit of normal
for age as per local laboratory; alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) < 5 times upper limit of normal as per local laboratory.
Patients with hyperbilirubinemia as a consequence of hyperhemolysis, or who
experience a sudden, profound change in the serum hemoglobin after a RBC
transfusion are not excluded.

Exclusion Criteria:

1. HLA typing prior to referral (consultation with HCT physician). However, if a subject
has had HLA typing with accompanying documentation that relatives were not HLA typed
and that a search of the unrelated donor registry was not performed the subject will
be considered eligible. Documentation will be reviewed and adjudicated by the Protocol
Officer or his/her designee.

2. Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.

3. Seropositivity for HIV.

4. Previous HCT.

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 (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.

10. Unwillingness to use approved contraception method from time of biologic assignment
until discontinuation of all immunosuppressive medications if assignment at biologic
assignment would be to donor arm.

Additional Eligibility Criteria for Transplant after Biologic Assignment to the Donor Arm:

Participants assigned to the Donor Arm at the time of biologic assignment are subject to
additional transplant eligibility criteria as specified below. Additional, repeat clinical
assessments prior to transplant should be obtained in accordance with institutional
policies and standards of care in the interest of good clinical practice.

1. Participants who are receiving ≥8 packed red blood cell transfusions for ≥1 year or
have received ≥20 packed red blood cell transfusions (cumulative) will undergo liver
MRI for estimation of hepatic iron content. Liver biopsy is indicated for hepatic iron
content ≥7 mg Fe/gm liver dry weight. Histological examination must document the
absence of cirrhosis, bridging fibrosis and active hepatitis. The absence of bridging
fibrosis will be determined using the histological grading and staging scale as
described by Ishak and colleagues (1995) as described in the Manual of Operating
Procedures.

2. Cerebral MRI/MRA within 30 days prior to initiation of transplant conditioning. If
there is clinical or radiologic evidence of a recent neurologic event (such as stroke
or transient ischemic attack) subjects will be deferred for at least 6 months with
repeat cerebral MRI/MRA to ensure stabilization of the neurologic event prior to
proceeding to transplantation.

3. Absence of donor specific HLA antibodies (section 2.5)

4. 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.

5. The HLA-matched donor must be medically fit to donate and willing to donate bone
marrow.


Gender: All

Minimum Age: 15 Years

Maximum Age: 40 Years

Accepts healthy volunteers: No

Please note that this is written for scientific review, and if there are any questions or clarifications needed, please contact

Cancer Center Studies
1-866-574-5124

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