Neoplasms

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Immune System Diseases

Musculoskeletal Diseases

Nutritional and Metabolic Diseases

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Leukemia

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Osteoporosis

Lymphoma

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Bone Diseases

Bone Diseases, Metabolic

Metabolic Diseases

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

Acute Graft Versus Host Disease

Childhood Acute Lymphoblastic Leukemia

Lymphosarcoma

Bone Density Conservation Agents

Micronutrients

All Drugs and Chemicals

Gastrointestinal Agents

Vitamins

Vitamin D

Cholecalciferol

Calcium

Calcium Carbonate

Calcium, Dietary

Trace Elements

Hormones

Antacids

Anti-Ulcer Agents

Vitamin D3

Calciferol

Nutritional counseling + supplementation with calcium, 1000mg/day + vitamin D, 800 units/day, for a 2 year period

Calcium carbonate 100mg/day (Tums), vitamin D 800 units/day

Calcium carbonate (Tums), vitamin D

Placebo

Sue C. Kaste, D.O.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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

St. Jude Children's Research Hospital

Placebo Group

Supplement Group

424 patients were enrolled into the study, 149 were ineligible for randomization.

Patients Ineligible for Randomization

Total

Age, Continuous

Sex: Female, Male

Sue Kaste, DO

12 Month BMD Z-Score Calculation where N=109

24 Month BMD Z-Score calculation where N=91

36 Month (End of Study) BMD Z-Score calculation where N=84

Baseline

12 Months

24 Months

36 Months (study end)

Placebo Group (Placebo Comparator 1A): Patients who received placebo pills.

CVD Supplement Group (Experimental 1B): Patients who received calcium and vitamin D supplementation.

Supplement

Of the 275 pts identified with BMD z-scores \< 0, 134 were randomized to the placebo group and 141 to the supplement group. Bone Mineral Density QCT Z-scores were calculated at baseline, 12 months, 24 months, and at 36 months or study end.

Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD)

Male

Female

Baseline participants were assessed to determine whether gender was a pre-disposing factor for bone mineral density.

Bone Mineral Density in Male and Female ALL Survivors

365 white patients were eligible for the study

White

Non-white

Assess baseline participants to determine whether race contributed to bone mineral density.

Bone Mineral Density by Race of ALL Survivors

98 patients between the ages of 9 and 13 were eligible for the study

9 to 13 Years

139 patients between the ages of 13 and 18 were eligible for the study

13 to 18 Years

74 patients between the ages of 18 and 22 were eligible for the study

18 to 22 Years

113 patients greater than 22 years of age were eligible for the study

Above 22 Years

Assess baseline participants to determine whether age was a contributing factor in bone mineral density.

Bone Mineral Density by Age Group of ALL Survivors

275 received a QCT and 121 received a DXA scan. 121 paired scans were evaluated.

134 patients were assessed at baseline using the QCT scan.

Placebo - (QCT)

60 of the 134 baseline patients also had a DXA scan.

Placebo - (DXA)

141 patients were assessed at baseline using the QCT scan.

Supplement - (QCT)

61 of the 141 baseline patients also had a DXA scan.

Supplement - (DXA)

275 patients were assessed at baseline and received a QCT Scan. 121 patients were also assessed using the DEXA Scan. Comparison of the two methods used 121 paired studies to arrive at a correlation coefficient.

Quantitative Computed Tomography (QCT) and Dual Energy X-ray Absorptiometry (DXA) Scan Scores for Bone Mineral Density.

218 patients were assessed at 12 months and received a QCT Scan. 94 patients were also assessed using the DEXA Scan. Comparison of the two methods used 94 paired studies to arrive at a correlation coefficient.

109 patients were assessed at 12 months using the QCT scan.

47 of the 109 patients assessed at 12 months also had a DXA scan.

218 patients were assessed at the 12 months interval and received a QCT Scan. 94 patients were also assessed using the DXA Scan. Comparison of the two methods used 94 paired studies to arrive at a correlation.

188 patients were assessed at baseline and received a QCT Scan. 90 patients were also assessed using the DEXA Scan. Comparison of the two methods used 90 paired studies to arrive at a correlation coefficient.

91 patients were assessed at 24 months using the QCT scan.

39 of the 91 patients assessed at 24 months also had a DXA scan.

97 patients were assessed at 24 months using the QCT scan.

51 of the 97 patients assessed at 24 months also had a DXA scan.

188 patients were assessed at the 24 months interval and received a QCT Scan. 90 patients were also assessed using the DXA Scan. Comparison of the two methods used 90 paired studies to arrive at a correlation.

180 patients were assessed at 36 months and received a QCT Scan. 89 patients were also assessed using the DXA Scan. Comparison of the two methods used 89 paired studies to arrive at a correlation coefficient.

84 patients were assessed at 36 months using the QCT scan.

36 of the 84 patients assessed at 36 months also had a DXA scan.

96 patients were assessed at 36 months using the QCT scan.

53 of the 96 patients assessed at 36 months also had a DXA scan.

180 patients were assessed at the 36 months interval and received a QCT Scan. 89 patients were also assessed using the DEXA Scan. Comparison of the two methods produced 89 paired studies to arrive at a correlation.

The AA genotype was observed in 68 (16.31%) out of 417 participants, with a median BMD Z score (a unit-less measure comparing to the age and gender matched national average) of -0.56.

Apa 1 - AA Genotype

The Aa genotype was observed in 104 (24.94%) out of 417 participants, with a median BMD Z score of -0.44.

Apa 1 - Aa Genotype

The aa genotype was present in 49 (11.75%) out of 417 participants, with a median BMD Z score of -0.57.

Apa 1 - aa Genotype

Of the 424 patients screened, 417 participants consented for genetic testing. Of the 417 patients screened for the Apa 1 vitamin D receptor, only 68 had the AA genotype, 104 had the Aa genotype, and 49 had the aa genotype.

Mean QCT Z-Score by Apa1 Vitamin D Receptor Genotype

The BB genotype was observed in 41 (09.83%) out of 417 participants, with a median BMD Z score (a unit-less measure comparing to the age and gender matched national average) of -0.5.

Bsm - BB Genotype

The Bb genotype was observed in 65 (15.59%) out of 417 participants, with a median BMD Z score of -0.17.

Bsm - Bb Genotype

The bb genotype was observed in 77 (18.47%) out of 417 participants, with a median BMD Z score of -0.17.

Bsm - bb Genotype

Of the 424 patients screened, 417 participants consented for genetic testing. Of the 417 patients screened for the Bsm 1 vitamin D receptor, only 41 had the BB genotype, 65 had the Bb genotype, and 77 had the bb genotype.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors	NCT00186901	Leukemia, Lymph... Osteoporosis	Calcium carbona... Placebo	-	St. Jude Children's Research Hospital
A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors	NCT00186901	Leukemia, Lymph... Osteoporosis	Calcium carbona... Placebo	-	St. Jude Children's Research Hospital
A Severity-Adapted Clinical Trial of Diminished Bone Mineral Density in Acute Lymphoblastic Leukemia Survivors	NCT00186901	Leukemia, Lymph... Osteoporosis	Calcium carbona... Placebo	-	St. Jude Children's Research Hospital

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