Clinical trial NCT02843347: STRIDE Biorepository
Official title: 1503 BMT CTN STRIDE Biorepository
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Anemia, Sickle Cell
Keywords: Biorepository
Genetics
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-07-25
Enrollment: 200
Sex: ALL
Minimum age (years): 15
Maximum age (years): 40
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The biorepository will consist of research participants from the main study who consent to having extra blood drawn and stored for the purpose of future genetic testing.

Brief summary: The STRIDE Biorepository is an optional substudy available to participants in "Bone Marrow Transplantation vs Standard of Care in Patients with Severe Sickle Cell Disease (BMT CTN 1503) (STRIDE)".

Detailed description: A subset of sites for the main study "Bone Marrow Transplantation vs Standard of Care in Patients with Severe Sickle Cell Disease (BMT CTN 1503) (STRIDE)" (NCT02766465) will also participate in the biorepository portion of the study. The purpose of the biorepository is to examine DNA to learn if certain genes predict who will have serious complications of sickle cell disease. The STRIDE Biorepository is an optional substudy available to individuals enrolled in the main study, who are at a participating site. Participants in the main study who consent to take part in the biorepository will have blood drawn at the Baseline Visit. This blood will be shipped to Emory University in Atlanta Georgia and stored for future research.

Eligibility criteria: Inclusion Criteria:

* Age at least 15 years old to less than 41 years old
* Severe sickle cell disease \[any clinically significant sickle genotype, for example, Hemoglobin SS (Hb SS), Hemoglobin SC (Hb SC) or Hemoglobin SBeta thalassemia (Hb Sβ), or Hemoglobin S-OArab genotype\] with at least 1 of the following manifestations:

  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 or referral (required intravenous pain management in the outpatient or inpatient hospital setting);
  4. Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving 8 or more transfusions 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 at least 6 months.
* 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 (MUGA) Scan
  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 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.

Exclusion Criteria:

* Human Leukocyte Antigen (HLA) typing prior to referral (consultation with hematopoietic cell transplantation (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.
* Uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment.
* Seropositivity for HIV
* Previous HCT or solid organ transplant
* Participation in a clinical trial in which the patient received an investigational drug or device must be discontinued at enrollment.
* 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 (determined by referring physician).
* Pregnant or breast feeding females.
* Inability to receive HCT due to alloimmunization, defined as the inability to receive packed red blood cell (pRBC) transfusion therapy.

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.

* Participants must have liver magnetic resonance imaging (MRI) (at least 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 (at least 90 days prior to initiation of transplant conditioning).
* Cerebral MRI/magnetic resonance angiogram (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.
* Documentation of participant's willingness to use approved contraception method until discontinuation of all immunosuppressive medications. This is to be documented in the medical record corresponding with the consent conference.
* Have a suitably matched HLA donor
* Willing and able to donate bone marrow
* Absence of anti-donor HLA antibodies

Primary outcomes:
measure: Genetic variants in persons with sickle cell disease
timeFrame: Baseline Visit
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: Benioff Children's Hospital at Oakland
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Gainesville
country: United States
facility: University of Florida Gainsville
state: Florida
city: Hollywood
country: United States
facility: Foundation for Sickle Cell Research/Florida Sickle Inc.
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Grady Hospital
state: Georgia
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory Children's Center
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Augusta University Medical Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: New Orleans
country: United States
facility: Children's Hospital of New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Oschner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute/Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston University
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute/Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University/St. Louis Children's Hospital
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Newark
country: United States
facility: Newark Beth Israel Medical Center
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center/Albert Einstein School of Medicine
state: New York
city: Brooklyn
country: United States
facility: New York Presbyterian Brooklyn Methodist Hospital
state: New York
city: New Hyde Park
country: United States
facility: Cohen Children's Medical Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospital at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Oregon Health Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Houston
country: United States
facility: University of Texas Health Sciences Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine/The Methodist Hospital
state: Texas
city: Houston
country: United States
facility: University of Texas/MD Anderson CRC
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: Emory University
name: Lakshmanan Krishnamurti, MD
role: PRINCIPAL_INVESTIGATOR
References: