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

Active, not recruiting

• Conditions: Juvenile Myelomonocytic Leukemia; Chronic Myelogenous Leukemia; Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia/Lymphoma; Myelodysplasia

• Registration Number: NCT02338479
• Lead Sponsor: Center for International Blood and Marrow Transplant Research

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.

Study Timeline

• Study First Submitted: 2015-01-12
• Study First Submitted QC: 2015-01-12
• Study First Posted: 2015-01-14
• Study Start: 2015-03
• Primary Completion: 2020-09
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-08
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 340

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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 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 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 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 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
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

Trial Locations

Locations (32)

Children's Healthcare of Atlanta; 🇺🇸 Atlanta, Georgia, United States

Nationwide Children's Hospital; 🇺🇸 Columbus, Ohio, United States

Dana Farber Cancer Institute - Pediatrics; 🇺🇸 Boston, Massachusetts, United States

Westchester Medical Center; 🇺🇸 Valhalla, New York, United States

University Hospitals Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

Mayo Clinic; 🇺🇸 Scottsdale, Arizona, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

University of California San Francisco Medical Center; 🇺🇸 San Francisco, California, United States

Children's Hospital of Los Angeles; 🇺🇸 Los Angeles, California, United States

UCLA Center for Health Sciences; 🇺🇸 Los Angeles, California, United States

Children's Hospital & Research Center - Oakland; 🇺🇸 Oakland, California, United States

All Children's Hospital; 🇺🇸 Saint Petersburg, Florida, United States

University of Arizona Medical Center; 🇺🇸 Tucson, Arizona, United States

The Children's Mercy Hospitals and Clinics; 🇺🇸 Kansas City, Missouri, United States

Ann and Robert H. Lurie Children's Hospital of Chicago; 🇺🇸 Chicago, Illinois, United States

Indiana University Hospital/Riley Hospital for Children; 🇺🇸 Indianapolis, Indiana, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Levine Children's Hospital; 🇺🇸 Charlotte, North Carolina, United States

University of North Carolina Hospitals; 🇺🇸 Chapel Hill, North Carolina, United States

Duke University Medical Center - Pediatrics; 🇺🇸 Durham, North Carolina, United States

Oregon Health and Science University - Doernbecher Children's Hospital; 🇺🇸 Portland, Oregon, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Medical University of South Carolina; 🇺🇸 Charleston, South Carolina, United States

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States

Texas Transplant Institute; 🇺🇸 San Antonio, Texas, United States

Children's Medical Center Dallas; 🇺🇸 Dallas, Texas, United States

Primary Children's Hospital; 🇺🇸 Salt Lake City, Utah, United States

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Children's Hospital of Wisconsin; 🇺🇸 Milwaukee, Wisconsin, United States

Washington University/St. Louis Children's Hospital; 🇺🇸 Saint Louis, Missouri, United States