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

April 3, 2017 updated by: St. Jude Children's Research Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

429

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital
      • Memphis, Tennessee, United States, 38163
        • Metabolic Bone Center at the University of Tennessee
      • Memphis, Tennessee, United States, 38163
        • Preventive Medicine, University of Tennessee

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of Taking Calcium and Vitamin D Supplements on Bone Mineral Density (BMD)
Time Frame: Baseline, 12 months, 24 months, and at 36 months or study end
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
Time Frame: Baseline
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
Time Frame: Baseline
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
Time Frame: Baseline
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.
Time Frame: Baseline
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.
Time Frame: 12 months
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.
Time Frame: 24 months
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.
Time Frame: 36 months
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
Time Frame: At enrollment
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
Time Frame: At enrollment
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Investigators

  • Principal Investigator: Sue C. Kaste, D.O., St. Jude Children's Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2000

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

September 1, 2011

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 16, 2005

Study Record Updates

Last Update Posted (Actual)

May 10, 2017

Last Update Submitted That Met QC Criteria

April 3, 2017

Last Verified

December 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • BONEII

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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