Clinical trial NCT00186901: A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors
Official title: Diminished Bone Mineral Density in Survivors of Childhood Acute Lymphoblastic Leukemia (ALL): A Severity-Adapted Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Leukemia, Lymphoblastic, Acute
Osteoporosis
Keywords: Bone Density
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
First posted: 2005-09-16
Enrollment: 429
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Research studies have shown that children who are long-term survivors of childhood leukemia may be at greater risk for early bone loss called osteoporosis. This bone loss may lead to a greater risk of broken bones and other spine and bone problems. However, researchers still do not know much about how frequently this long-term side effect may occur and how severe the problem is.

St. Jude Children's Research Hospital researchers want to determine the frequency and severity of this side effect. They are also studying whether taking calcium and Vitamin D supplements can help children at risk for osteoporosis and if certain factors can be identified -- such as age at diagnosis, cancer treatments, or family history -- that may increase the chances of having osteoporosis. Researchers will take an x-ray study called quantitative computed tomography (QCT) to measure bone mineral density (BMD). The BMD is a measure of bone strength. If a subject's BMD falls below the average, he/she will be assigned to one of two groups. Subjects will be randomly assigned (like tossing a coin) to receive calcium and vitamin D pills. The other half will receive placebo pills that look like the calcium and vitamin D pills.

Detailed description: The main objectives of the study are:

* To estimate, using quantitative computed tomography (QCT), the prevalence of diminished bone mineral density (BMD) in patients treated with contemporary, protocol-based multiagent chemotherapy (+cranial irradiation) for childhood acute lymphoblastic leukemia (ALL).
* To investigate possible risk factors for the development of diminished BMD in patients treated with contemporary protocol-based therapy for childhood ALL. Factors to be examined include patient characteristics (age at the time of treatment, gender, race, body mass index, physical activity and nutritional status, menarchal status, oral contraceptive use, growth hormone therapy, smoking and alcohol intake, birth weight, fracture history); treatment effects (intensity of treatment with antimetabolites and glucocorticoids; history of cranial irradiation); and genetic predisposition (i.e., vitamin D and CYP3A4 receptor polymorphism and family history of osteoporosis).
* To evaluate, in a prospective placebo-controlled double-blinded randomized trial, the effects of vitamin D and calcium supplementation in addition to nutritional counseling on BMD in patients with BMD scores below the mean for age- and gender-matched controls, compared to an educational program of nutritional counseling alone.

Secondary Aim

* To evaluate, in a prospective randomized trial, the correlation between BMD as determined by QCT and BMD as determined by dual energy x-ray absorptiometry (DEXA) in patients with BMD more than one standard deviation (SD) below the mean for age- and gender-matched controls.

Eligibility criteria: Inclusion Criteria:

* Patient is a survivor of acute lymphoblastic leukemia.
* Patient was treated on St. Jude Children's Research Hospital's Total XI, XII, or XIII treatment protocol.
* Patient is at least five years out from completion of therapy and is in first remission

Exclusion Criteria:

* Active disease
* Pregnant or lactating females
* Inability to chew and swallow pills
* Currently taking more than 800 mg supplemental calcium or 800 IU vitamin D
* Anemia

Primary outcomes:
measure: Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD)
timeFrame: Baseline, 12 months, 24 months, and at 36 months or study end
measure: Bone Mineral Density in Male and Female ALL Survivors
timeFrame: Baseline
measure: Bone Mineral Density by Race of ALL Survivors
timeFrame: Baseline
measure: Bone Mineral Density by Age Group of ALL Survivors
timeFrame: Baseline
Secondary outcomes:
measure: Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
timeFrame: Baseline
measure: Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
timeFrame: 12 months
measure: Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
timeFrame: 24 months
measure: Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.
timeFrame: 36 months
measure: Mean QCT Z-Score by Apa1 Vitamin D Receptor Genotype
timeFrame: At enrollment
measure: Mean QCT Z-Score by Bsm 1 Vitamin D Receptor Genotype
timeFrame: At enrollment
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
city: Memphis
country: United States
facility: Metabolic Bone Center at the University of Tennessee
state: Tennessee
city: Memphis
country: United States
facility: Preventive Medicine, University of Tennessee
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Sue C. Kaste, D.O.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kaste SC, Rai SN, Fleming K, McCammon EA, Tylavsky FA, Danish RK, Rose SR, Sitter CD, Pui CH, Hudson MM. Changes in bone mineral density in survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2006 Jan;46(1):77-87. doi: 10.1002/pbc.20553.
citation: Crom DB, Tyc VL, Rai SN, Deng X, Hudson MM, Booth A, Rodrigues LN, Zhang L, McCammon E, Kaste SC. Retention of survivors of acute lymphoblastic leukemia in a longitudinal study of bone mineral density. J Child Health Care. 2006 Dec;10(4):337-50. doi: 10.1177/1367493506067886.