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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Juvenile Myelomonocytic Leukemia; Acute Myelogenous Leukemia; Chronic Myelogenous Leukemia; Myelodysplasia; Acute Lymphoblastic Leukemia/Lymphoma

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 Type: Observational
• Enrollment (Actual): 340

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic
    • Tucson, Arizona, United States, 85724
      • University of Arizona Medical Center
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital of Los Angeles
    • Los Angeles, California, United States, 90095
      • UCLA Center for Health Sciences
    • Oakland, California, United States, 94609
      • Children's Hospital & Research Center - Oakland
    • San Francisco, California, United States, 94143
      • University of California San Francisco Medical Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Medical Center
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60601
      • Ann and Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Hospital/Riley Hospital for Children
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute - Pediatrics
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • The Children's Mercy Hospitals and Clinics
    • Saint Louis, Missouri, United States, 63110
      • Washington University/St. Louis Children's Hospital
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Valhalla, New York, United States, 10595
      • Westchester Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Hospitals
    • Charlotte, North Carolina, United States, 28203
      • Levine Children's Hospital
    • Durham, North Carolina, United States, 27705
      • Duke University Medical Center - Pediatrics
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Case Medical Center
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University - Doernbecher Children's Hospital
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37235
      • Vanderbilt University Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • Children's Medical Center Dallas
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Institute
  • Utah
    • Salt Lake City, Utah, United States, 84111
      • Primary Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 22 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Center for International Blood and Marrow Transplant Research
• Collaborators: National Marrow Donor Program; Pediatric Blood and Marrow Transplant Consortium

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2015
• Primary Completion (ACTUAL): September 1, 2020
• Study Completion (ANTICIPATED): December 1, 2023

Study Registration Dates

• First Submitted: January 12, 2015
• First Submitted That Met QC Criteria: January 12, 2015
• First Posted (ESTIMATE): January 14, 2015

Study Record Updates

• Last Update Posted (ACTUAL): February 8, 2023
• Last Update Submitted That Met QC Criteria: February 7, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Lymphoid; Hematologic Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Juvenile; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: 13-TLEC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No