A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors

Study Overview
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Brief Summary
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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
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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.

Official Title
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Diminished Bone Mineral Density in Survivors of Childhood Acute Lymphoblastic Leukemia (ALL): A Severity-Adapted Clinical Trial

Conditions
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Leukemia, Lymphoblastic, Acute, Osteoporosis

Intervention / Treatment
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* Drug: Calcium carbonate (Tums), vitamin D
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1A<br>Nutritional counseling + placebo | Other: Placebo<br>* Placebo<br>|
| Experimental: 1B<br>Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period | Drug: Calcium carbonate (Tums), vitamin D<br>* Calcium carbonate 100mg/day (Tums), vitamin D 800 units/day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD) | The effect of taking calcium and vitamin D supplements was measured using Quantitative Computed Tomography (QCT) to calculate a QTC Z score. A standardized Z-score was calculated to indicate the difference between the patient's Bone Mineral Density (BMD) and the mean value for age and gender-appropriate controls. Z-scores from 0 to +2 are considered normal, above +2 are considered to be elevated, from 0 to -1 are considered to represent a mild BMD deficit, between -1 and -2 are considered to represent moderate deficits, and below -2 are considered to represent severe deficits. | Baseline, 12 months, 24 months, and at 36 months or study end | 
| Bone Mineral Density in Male and Female ALL Survivors | Using bone mineral density Z-score, assess relationship between predisposing factors (gender) and bone mineral density; a negative value indicates a deficit in bone mineral density. | Baseline | 
| Bone Mineral Density by Race of ALL Survivors | Using bone mineral density Z-score, assess relationship between predisposing factors (race) and bone mineral density; a negative value indicates a deficit in bone mineral density. | Baseline | 
| Bone Mineral Density by Age Group of ALL Survivors | Using bone mineral density Z-score, assess relationship between predisposing factors (age groups) and bone mineral density; a negative value indicates a deficit in bone mineral density. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. | To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 121 patients at baseline were assessed by both method the QCT and DXA methods to assess Bone Mineral Density. | Baseline | 
| Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. | To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 218 patients were assessed at 12 months for QCT. 94 were evaluated using DXA. 94 patients received both scans. | 12 months | 
| Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. | To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 188 patients were assessed at 24 months by the QCT method and 90 were evaluated using the DXA methods to assess Bone Mineral Density. 90 patients received both scans. | 24 months | 
| Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density. | To compare the bone mineral density scores determined by Quantitative Computed Tomography (QCT) with those determined by dual energy x-ray absorptiometry (DXA) scan. 180 patients were assessed at 36 months by the QCT method and 89 were evaluated using the DXA methods to assess Bone Mineral Density. 89 patients received both scans. | 36 months | 
| Mean QCT Z-Score by Apa1 Vitamin D Receptor Genotype | The Apa1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood | At enrollment | 
| Mean QCT Z-Score by Bsm 1 Vitamin D Receptor Genotype | The Bsm1 Vitamin D Receptor has been associated with bone mineral density and bone turnover markers in various patient cohorts but has not been investigated I survivors of childhood | At enrollment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bone Density