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Imaging and Blood Biomarker Evaluation of Engraftment after Allogeneic Hematopoietic Stem Cell Transplant, REVEAL Study
Trial Status: active
This trial aims to find new tests that could help determine if newly infused bone marrow cells are growing well after bone marrow transplant (hematopoietic stem cell transplant) or if new bone marrow cells are needed in patients who have undergone or will undergo a bone marrow transplant. The process of bone marrow transplant involves giving chemotherapy and or radiation that removes healthy blood stem cells and leukemia or cancer cells. Then, healthy blood stem cells from another person are infused through a vein (usually through a central line). These cells travel to the bone marrow, the factory of the blood, and make new blood cells, including white blood cells, red blood cells, and platelets. This process typically takes 4-6 weeks. During this time, there is currently no way to tell if the new cells have settled in the bone marrow and are generating cells that can be seen in the blood or if they are not growing well and more blood stem cells may be needed. One of the risks of bone marrow transplant is that the newly infused cells don’t grow and make new white blood cells (neutrophils). In this case, the risk of infections is very high. This risk more often occurs when the donor is mismatched (such as when the half-matched parent or sibling is donor) or cord blood donor is used, and patients are undergoing a transplant with one of these donor sources. Usually, doctors wait for about 4 weeks to give the cells a chance to grow, and then, if the new cells have not grown, the process begins to find (or collect), and give new blood stem cells. Diagnostic procedures, such as 18F-FLT PET/CT and blood tests (such as TK-1), may help doctors understand what is happening inside the bone marrow. Information gained from this trial may help doctors learn if these tests could be used to help diagnose when new blood stem cells do not grow (marrow failure) earlier which could help treat patients earlier.
Inclusion Criteria
INCLUSION CRITERIA - ARMS A AND B
Ability to undergo 18F FLT imaging without sedation
Patients > 4 years of age and less than 60 years of age at highest risk for graft failure: cord blood HSCT, haplo HSCT, or lack of engraftment by day 28
Diagnosed with a condition for which hematopoietic stem cell transplant (HSCT) is standard of care and HSCT is planned (Arm A) or occurred (Arm B)
Able to perform FLT imaging without anesthesia
In morphologic remission prior to HSCT
Patient or guardian able to give informed consent
No investigational therapies within past 28 days Karnofsky or Lansky performance status > 60%
INCLUSION CRITERIA - ARM A RECIPIENTS
Cord blood recipients: Absence of donor specific antibodies to cord human leukocyte antigen (HLA)
Haplo-identical recipients: > 5/10 and < 7/8 allele mismatch donor
Diagnosed with a condition for which myeloablative hematopoietic stem cell transplant (HSCT) is standard of care and HSCT is planned
Total bilirubin < 2.5 mg/dL (unless documented Gilbert’s syndrome) and transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) < 5 x the upper limit of normal
Forced expiratory volume in 1 second (FEV1) > 80% post-bronchiolator and carbon monoxide diffusing capability test (DLCO) adjusted (Adj) > 70% (performed pre-HSCT if age appropriate) and oxygen saturation (Sa02) > 94% on room air
Ejection fraction > 50% (performed pre-HSCT)
INCLUSION CRITERIA - ARM B RECIPIENTS
Non-engraftment recipients of cord or haplo-identical HSCT: primary graft failure as defined by absolute neutrophil count (ANC) not > 500 for 3 consecutive days and at least 24 days after HSCT
INCLUSION CRITERIA - DONORS
2 cords and >= 4/6 match to recipient for each (as per current National Marrow Donor guidelines), with a dose >= 2 x 10e6 CD34 cells/kg for each cord OR > 5/10 and < 7/8 allele mismatch related donor
Institutional guidelines met for donor suitability
Exclusion Criteria
EXCLUSION CRITERIA - TRANSPLANT RECIPIENTS ARMS A AND B
History of psychiatric disorder which may compromise compliance with transplant protocol, or which does not allow for appropriate informed consent
Clinically significant systemic illness with manifestations of significant organ dysfunction which, in the judgment of the principal investigator (PI), or co-investigator (I), would render the patient unlikely to tolerate the protocol therapy or complete the study
Presence of active malignancy from an organ system other than hematopoietic
Pregnant or lactating females
Patients who are unable or unwilling to use effective form(s) of contraception during the course of the study
Prior history of fluorothymidine allergy or intolerance
Decline enrollment on Center for International Blood and Marrow Transplantation Research (CIBMTR) research protocol
Additional locations may be listed on ClinicalTrials.gov for NCT03541889.
Locations matching your search criteria
United States
Georgia
Atlanta
Children's Healthcare of Atlanta - Arthur M Blank Hospital
I. Evaluate whether fluorothymidine F-18 (FLT) uptake distinguishes delayed from graft failure after hematopoietic stem cell transplantation (HSCT).
SECONDARY OBJECTIVES:
I. Map the cellular pathway to subclinical engraftment after cord blood and haplo-identical engraftment using FLT imaging, identifying the earliest marrow site of settling (Arm A).
II. Evaluate the safety of FLT for patients at highest risk for graft failure (Arms A and B).
III. Evaluate safety of FLT for patients at highest risk for graft failure.
IV. Determine whether levels of TK1, an investigational blood biomarker, correlate with graft failure, or delayed engraftment, compared to those with on-time engraftment.
V. Explore whether cellular, cytokine, or chemokine markers of subclinical engraftment.
VI. Explore whether FLT uptake or biomarker studies correlate with relapse of malignant disease or residual disease or correlates with other significant HSCT events such as sinusoidal obstructive disease of the liver, graft-versus-host disease, and infections.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM A (CORD BLOOD AND HAPLO-IDENTICAL RECIPIENTS): Patients receive fluorothymidine F-18 intravenously (IV) and undergo positron emission tomography (PET)/computed tomography (CT) over 95 minutes on day -1 (the day before HSCT), and days 9 and 28 after HSCT. Patients also undergo collection of blood samples on day -1 (the day before HSCT), and days 9 and 28 after HSCT.
ARM B (NON-ENGRAFTED RECIPIENTS): Beginning 20 days after cord or haplo-identical HSCT, patients receive fluorothymidine F-18 IV and undergo PET/CT over 95 minutes once. Patients also undergo collection of blood sample on the day of imaging scan and at engraftment (if possible).
Trial PhasePhase I
Trial Typediagnostic
Lead OrganizationChildren's Healthcare of Atlanta - Arthur M Blank Hospital
