Natural History and Biology of Long-Term Late Effects Following Hematopoietic Cell Transplant for Childhood Hematologic Malignancies

Sponsor

Center for International Blood and Marrow Transplant Research (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT02338479

Collaborator

Pediatric Blood and Marrow Transplant Consortium (Other), National Marrow Donor Program (Other)

340

Enrollment

Locations

Anticipated Duration (Months)

10.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Lymphoblastic Leukemia/Lymphoma Myelodysplasia Acute Myelogenous Leukemia Juvenile Myelomonocytic Leukemia Chronic Myelogenous Leukemia

Detailed Description

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.

Study Design

Study Type:

Observational

Actual Enrollment :

340 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Natural History and Biology of Long-Term Late Effects Following Hematopoietic Cell Transplant for Childhood Hematologic Malignancies

Actual Study Start Date :

Mar 1, 2015

Actual Primary Completion Date :

Sep 1, 2020

Anticipated Study Completion Date :

Dec 1, 2022

Outcome Measures

Primary Outcome Measures

To report the incidence of chronic kidney disease (CKD), metabolic syndrome, and osteopenia [Baseline to 1 and 2 years following allogeneic HCT for hematologic malignancy]

Secondary Outcome Measures

To identify prognostic risk factors for the development and progression of post-HCT CKD, metabolic syndrome, and osteopenia [Baseline to 1 and 2 years following HCT]
To investigate potential associations of systemic hypertension as measured with intermittent blood pressure assessment with proteinuria, acute kidney injury, and CKD [Baseline to 100 days, and at 1 and 2 years following HCT]
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 [Baseline to 180 days, and at 1 and 2 years following HCT]
To explore potential association of the protein biomarker elafin in the urine at with the development of CKD [Baseline to 180 days, and at 1 and 2 years following HCT]
To report levels of fasting triglycerides, low-density lipoprotein, high-density lipoprotein, insulin, and glucose levels [Baseline to 100 days, and at 1 and 2 years following HCT]
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 [Baseline to 1 and 2 years following HCT]
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 [Baseline to 1 and 2 years following HCT]
To report levels of markers of bone turnover including serum osteocalcin, bone specific alkaline phosphatase, and urine N-telopeptide [Baseline to 30 days, 100 days, and at 1 and 2 years following HCT]
To develop a repository for plasma to be used in future investigation of HCT-associated late effects [Baseline, 30 days, 100 days, and at 1 and 2 years following HCT]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 22 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age less than 22 years at admission for HCT
Planned allogeneic HCT from any donor and stem cell source. There are no study-specific criteria for HLA-matching
Disease and disease status criteria
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
Myelodysplasia (regardless of subtype) with less than 10% marrow blasts within 30 days of the start of the conditioning regimen; OR
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
Juvenile myelomonocytic leukemia; OR
Chronic myelogenous leukemia excluding refractory blast crisis.
Planned myeloablative conditioning regimen, defined as a regimen including one of the following as a backbone agent:
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
Total Body Irradiation ≥ 1200 cGy fractionated; OR
Treosulfan ≥ 30 g/m2 total dose IV
Enrollment in the following NMDP research protocols:
Protocol for a Research Database for Hematopoietic Cell Transplantation, Other Cellular Therapies and Marrow Toxicity Injuries
Protocol for a Research Sample Repository for Allogeneic Hematopoietic Stem Cell Transplantation and Marrow Toxic Injuries
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:

Prior allogeneic or autologous HCT
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
Patients with osteopenia or osteoporosis treated with a bisphosphonate medication at any time prior to enrollment
Patients with preexisting diabetes or hyperglycemia treated with insulin or oral hypoglycemic medication at the time of enrollment
Patients with uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment
Karnofsky performance score or Lansky Play-Performance Scale Score <60 at the time of study enrollment
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Scottsdale	Arizona	United States	85259-5499
2	University of Arizona Medical Center	Tucson	Arizona	United States	85724
3	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
4	UCLA Center for Health Sciences	Los Angeles	California	United States	90095
5	Children's Hospital & Research Center - Oakland	Oakland	California	United States	94609
6	University of California San Francisco Medical Center	San Francisco	California	United States	94143
7	University of Colorado	Aurora	Colorado	United States	80045
8	Children's National Medical Center	Washington	District of Columbia	United States	20010
9	All Children's Hospital	Saint Petersburg	Florida	United States	33701
10	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
11	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60601
12	Indiana University Hospital/Riley Hospital for Children	Indianapolis	Indiana	United States	46202
13	Dana Farber Cancer Institute - Pediatrics	Boston	Massachusetts	United States	02215
14	University of Michigan	Ann Arbor	Michigan	United States	48109
15	The Children's Mercy Hospitals and Clinics	Kansas City	Missouri	United States	64108
16	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
17	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
18	Westchester Medical Center	Valhalla	New York	United States	10595
19	University of North Carolina Hospitals	Chapel Hill	North Carolina	United States	27599
20	Levine Children's Hospital	Charlotte	North Carolina	United States	28203
21	Duke University Medical Center - Pediatrics	Durham	North Carolina	United States	27705
22	University Hospitals Case Medical Center	Cleveland	Ohio	United States	44106
23	Cleveland Clinic	Cleveland	Ohio	United States	44195
24	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
25	Oregon Health and Science University - Doernbecher Children's Hospital	Portland	Oregon	United States	97239
26	Medical University of South Carolina	Charleston	South Carolina	United States	29425
27	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37235
28	Children's Medical Center Dallas	Dallas	Texas	United States	75235
29	Texas Transplant Institute	San Antonio	Texas	United States	78229
30	Primary Children's Hospital	Salt Lake City	Utah	United States	84111
31	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
32	Children's Hospital of Wisconsin	Milwaukee	Wisconsin	United States	53226