STRIDE Biorepository

Anemia, Sickle Cell Clinical Trial

Official title:

1503 BMT CTN STRIDE Biorepository

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02843347
• Other study ID #: IRB00089102
• Secondary ID: 1U01HL128566
• Status: Recruiting
• Start date: March 13, 2017
• Est. completion date: July 2023

Study information

• Verified date: February 2021
• Source: Emory University
• Contact: Lakshmanan Krishnamurti, MD
• Phone: 404-785-1112
• Email: lakshmanan.krishnamurti[@]emory.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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)".

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: July 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 40 Years

Eligibility

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 Sß),

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell

Intervention

Procedure:
• Blood draw
Three tubes of blood (28.5 mL in total) will be obtained at the Baseline Visit. The sample will be stored for future research.

Locations

Country	Name	City	State
United States	University of Michigan Medical Center	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Emory Children's Center	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Grady Hospital	Atlanta	Georgia
United States	Augusta University Medical Center	Augusta	Georgia
United States	Boston University	Boston	Massachusetts
United States	Dana Farber Cancer Institute/Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana Farber Cancer Institute/Massachusetts General Hospital	Boston	Massachusetts
United States	Montefiore Medical Center/Albert Einstein School of Medicine	Bronx	New York
United States	New York Presbyterian Brooklyn Methodist Hospital	Brooklyn	New York
United States	University of North Carolina Hospital at Chapel Hill	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	University of Chicago	Chicago	Illinois
United States	Ohio State University	Columbus	Ohio
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	University of Florida Gainsville	Gainesville	Florida
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Foundation for Sickle Cell Research/Florida Sickle Inc.	Hollywood	Florida
United States	Baylor College of Medicine/The Methodist Hospital	Houston	Texas
United States	University of Texas Health Sciences Center	Houston	Texas
United States	University of Texas/MD Anderson CRC	Houston	Texas
United States	University of Iowa	Iowa City	Iowa
United States	University of Miami	Miami	Florida
United States	Cohen Children's Medical Center	New Hyde Park	New York
United States	Children's Hospital of New Orleans	New Orleans	Louisiana
United States	Oschner Medical Center	New Orleans	Louisiana
United States	Icahn School of Medicine at Mount Sinai	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Newark Beth Israel Medical Center	Newark	New Jersey
United States	Benioff Children's Hospital at Oakland	Oakland	California
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health Sciences University	Portland	Oregon
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Genetic variants in persons with sickle cell disease	A biorepository will be established for future genetic research of sickle cell disease. Blood samples will be drawn from participants at the Baseline Visit and will be stored until analyzed. Analysis will include learning more about the genetics behind complications of sickle cell disease.	Baseline Visit