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

Acute Myelogenous Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02338479
• Other study ID #: 13-TLEC
• Status: Active, not recruiting
• Start date: March 2015
• Est. completion date: December 2023

Study information

• Verified date: February 2023
• Source: Center for International Blood and Marrow Transplant Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 340
• Est. completion date: December 2023
• Est. primary completion date: September 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 22 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia/Lymphoma
• Acute Myelogenous Leukemia
• Chronic Myelogenous Leukemia
• Hematologic Neoplasms
• Juvenile Myelomonocytic Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplasia
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Dana Farber Cancer Institute - Pediatrics	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	University of North Carolina Hospitals	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Ann and Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	University Hospitals Case Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Medical Center Dallas	Dallas	Texas
United States	Duke University Medical Center - Pediatrics	Durham	North Carolina
United States	Indiana University Hospital/Riley Hospital for Children	Indianapolis	Indiana
United States	The Children's Mercy Hospitals and Clinics	Kansas City	Missouri
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 of Wisconsin	Milwaukee	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Children's Hospital & Research Center - Oakland	Oakland	California
United States	Oregon Health and Science University - Doernbecher Children's Hospital	Portland	Oregon
United States	Washington University/St. Louis Children's Hospital	Saint Louis	Missouri
United States	All Children's Hospital	Saint Petersburg	Florida
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	Texas Transplant Institute	San Antonio	Texas
United States	University of California San Francisco Medical Center	San Francisco	California
United States	Mayo Clinic	Scottsdale	Arizona
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	University of Arizona Medical Center	Tucson	Arizona
United States	Westchester Medical Center	Valhalla	New York
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Center for International Blood and Marrow Transplant Research	National Marrow Donor Program, Pediatric Blood and Marrow Transplant Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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