Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02338479
Recruitment Status : Active, not recruiting
First Posted : January 14, 2015
Last Update Posted : May 16, 2019
Sponsor:
Collaborators:
Pediatric Blood and Marrow Transplant Consortium
National Marrow Donor Program
Information provided by (Responsible Party):
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.

Condition or disease
Acute Lymphoblastic Leukemia/Lymphoma Myelodysplasia Acute Myelogenous Leukemia Juvenile Myelomonocytic Leukemia Chronic Myelogenous Leukemia

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.

Layout table for study information
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 : March 2015
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : February 2020





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

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


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 22 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02338479


Locations
Show Show 32 study locations
Sponsors and Collaborators
Center for International Blood and Marrow Transplant Research
Pediatric Blood and Marrow Transplant Consortium
National Marrow Donor Program
Investigators
Layout table for investigator information
Study Chair: Christine Duncan, MD Dana-Farber Cancer Institute
Study Chair: K. Scott Baker, MD Fred Hutchinson Cancer Research Center
Layout table for additonal information
Responsible Party: Center for International Blood and Marrow Transplant Research
ClinicalTrials.gov Identifier: NCT02338479    
Other Study ID Numbers: 13-TLEC
First Posted: January 14, 2015    Key Record Dates
Last Update Posted: May 16, 2019
Last Verified: May 2019
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hematologic Neoplasms
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Juvenile
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Neoplasms by Site
Myelodysplastic-Myeloproliferative Diseases