Clinical trial NCT02338479: Natural History and Biology of Long-Term Late Effects Following Hematopoietic Cell Transplant for Childhood Hematologic Malignancies
Official title: Natural History and Biology of Long-Term Late Effects Following Hematopoietic Cell Transplant for Childhood Hematologic Malignancies
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Acute Lymphoblastic Leukemia/Lymphoma
Myelodysplasia
Acute Myelogenous Leukemia
Juvenile Myelomonocytic Leukemia
Chronic Myelogenous Leukemia
Lead sponsor: Center for International Blood and Marrow Transplant Research
Sponsor class: NETWORK
Collaborators: name: Pediatric Blood and Marrow Transplant Consortium
name: National Marrow Donor Program
First posted: 2015-01-14
Enrollment: 340
Sex: ALL
Maximum age (years): 22
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study will enroll is a nonrandomized prospective cohort undergoing HCT for treatment of childhood leukemia and myelodysplasia.

Brief summary: This is a prospective non-therapeutic study, assessing the long-term toxicity of pediatric HCT for hematologic malignancies. This study is a collaboration between the Pediatric Blood and Marrow Transplant Consortium (PBMTC), the Center for International Blood and Marrow Transplant Research (CIBMTR), the National Marrow Transplant Program (NMDP) and the Resource for Clinical Investigation in Blood and Marrow Transplantation (RCI-BMT) of the CIBMTR. The study will enroll pediatric patients who undergo myeloablative HCT for hematologic malignancies at PBMTC sites.

Detailed description: This is a prospective non-therapeutic study, assessing the long-term toxicity of pediatric HCT for hematologic malignancies. This study is a collaboration between the Pediatric Blood and Marrow Transplant Consortium (PBMTC), the Center for International Blood and Marrow Transplant Research (CIBMTR), the National Marrow Transplant Program (NMDP) and the Resource for Clinical Investigation in Blood and Marrow Transplantation (RCI-BMT) of the CIBMTR. The study will enroll pediatric patients who undergo myeloablative HCT for hematologic malignancies at PBMTC sites.

The study examines the hypothesis that survivors of pediatric HCT are at risk for late organ toxicity and they will have identifiable biomarkers present within the first two years following HCT which will be predictive for late adverse outcomes allowing for early identification of patients at risk.

Eligibility criteria: Inclusion Criteria:

1. Age less than 22 years at admission for HCT
2. Planned allogeneic HCT from any donor and stem cell source. There are no study-specific criteria for HLA-matching
3. Disease and disease status criteria

   1. Acute lymphoblastic leukemia/lymphoma in complete morphologic remission defined as a M1 marrow (\<5% blasts) with no evidence of active extramedullary disease within 30 days of the start of the conditioning regimen; OR
   2. Myelodysplasia (regardless of subtype) with less than 10% marrow blasts within 30 days of the start of the conditioning regimen; OR
   3. Acute myelogenous leukemia in complete morphologic remission defined as an M1 marrow (\<5% blasts) with no evidence of extramedullary disease within 30 days of the start of the conditioning regimen; OR
   4. Juvenile myelomonocytic leukemia; OR
   5. Chronic myelogenous leukemia excluding refractory blast crisis.
4. Planned myeloablative conditioning regimen, defined as a regimen including one of the following as a backbone agent:

   1. Busulfan ≥ 12.8 mg/kg total dose (IV or PO). PK-based dosing allowed, if the intent is total overall dose ≥ 12.8 mg/kg; OR
   2. Total Body Irradiation ≥ 1200 cGy fractionated; OR
   3. Treosulfan ≥ 30 g/m2 total dose IV
5. Enrollment in the following NMDP research protocols:

   1. Protocol for a Research Database for Hematopoietic Cell Transplantation, Other Cellular Therapies and Marrow Toxicity Injuries
   2. Protocol for a Research Sample Repository for Allogeneic Hematopoietic Stem Cell Transplantation and Marrow Toxic Injuries
6. Written informed consent document signed by patient if the age is greater than or equal to 18 years and the patient is developmentally able to provide consent. The informed consent document is to be signed by the parent or legal guardian if the patient's age is less than 18 years or if the patient is older than 18 years, but developmentally unable to provide consent. Assent will be obtained according to the guidelines of the patient's transplant institution.

Exclusion Criteria:

1. Prior allogeneic or autologous HCT
2. Patients with renal disease prior to the start of HCT conditioning requiring the use of dialysis at the time of enrollment and/or GFR \< 60 mL/min/1.73 m2
3. Patients with osteopenia or osteoporosis treated with a bisphosphonate medication at any time prior to enrollment
4. Patients with preexisting diabetes or hyperglycemia treated with insulin or oral hypoglycemic medication at the time of enrollment
5. Patients with uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment
6. Karnofsky performance score or Lansky Play-Performance Scale Score \<60 at the time of study enrollment
7. Known inherited or constitutional predisposition to cancer including, but not limited to Down Syndrome, Li-Fraumeni syndrome, Fanconi Anemia, and patients with BRCA1 and BRCA2 mutations

Primary outcomes:
measure: To report the incidence of chronic kidney disease (CKD), metabolic syndrome, and osteopenia
timeFrame: Baseline to 1 and 2 years following allogeneic HCT for hematologic malignancy
Secondary outcomes:
measure: To identify prognostic risk factors for the development and progression of post-HCT CKD, metabolic syndrome, and osteopenia
timeFrame: Baseline to 1 and 2 years following HCT
measure: To investigate potential associations of systemic hypertension as measured with intermittent blood pressure assessment with proteinuria, acute kidney injury, and CKD
timeFrame: Baseline to 100 days, and at 1 and 2 years following HCT
measure: To compare the results of GFR estimating equations based on serum cystatin C levels or serum creatinine to GFR measured by nuclear medicine GFR and/or 24-hour creatinine clearance
timeFrame: Baseline to 180 days, and at 1 and 2 years following HCT
measure: To explore potential association of the protein biomarker elafin in the urine at with the development of CKD
timeFrame: Baseline to 180 days, and at 1 and 2 years following HCT
measure: To report levels of fasting triglycerides, low-density lipoprotein, high-density lipoprotein, insulin, and glucose levels
timeFrame: Baseline to 100 days, and at 1 and 2 years following HCT
measure: To assess change in body composition including bone mineral density, body mass index, percent fat mass and lean body mass as measured by dual-energy absorptiometry
timeFrame: Baseline to 1 and 2 years following HCT
measure: To assess the presence of osteopenia prior to HCT and at 1-year and 2-years following HCT by x-ray in patients unable to undergo DXA without sedation
timeFrame: Baseline to 1 and 2 years following HCT
measure: To report levels of markers of bone turnover including serum osteocalcin, bone specific alkaline phosphatase, and urine N-telopeptide
timeFrame: Baseline to 30 days, 100 days, and at 1 and 2 years following HCT
measure: To develop a repository for plasma to be used in future investigation of HCT-associated late effects
timeFrame: Baseline, 30 days, 100 days, and at 1 and 2 years following HCT
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic
state: Arizona
city: Tucson
country: United States
facility: University of Arizona Medical Center
state: Arizona
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Los Angeles
country: United States
facility: UCLA Center for Health Sciences
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center - Oakland
state: California
city: San Francisco
country: United States
facility: University of California San Francisco Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Saint Petersburg
country: United States
facility: All Children's Hospital
state: Florida
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Hospital/Riley Hospital for Children
state: Indiana
city: Boston
country: United States
facility: Dana Farber Cancer Institute - Pediatrics
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Kansas City
country: United States
facility: The Children's Mercy Hospitals and Clinics
state: Missouri
city: Saint Louis
country: United States
facility: Washington University/St. Louis Children's Hospital
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Valhalla
country: United States
facility: Westchester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina Hospitals
state: North Carolina
city: Charlotte
country: United States
facility: Levine Children's Hospital
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center - Pediatrics
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University - Doernbecher Children's Hospital
state: Oregon
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Children's Medical Center Dallas
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute
state: Texas
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Children's Hospital of Wisconsin
state: Wisconsin
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Christine Duncan, MD
role: STUDY_CHAIR
affiliation: Fred Hutchinson Cancer Center
name: K. Scott Baker, MD
role: STUDY_CHAIR
References: