A Study of Actonel for the Prevention of Bone Loss

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if Actonel (risedronate) can help to prevent the development of osteoporosis (brittle and weak bones) caused by the steroid medication used to treat leukemia. The safety of this treatment in patients with ALL or LL will also be studied.

Detailed Description
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One of the side effects of using high dose corticosteroids for the treatment of ALL is osteoporosis. Risedronate is a medication that was designed to help prevent osteoporosis (brittle and weak bones). Before treatment you will receive a complete physical exam. You will have around 1 tablespoon of blood drawn for blood tests (these tests are in addition to the routine blood tests you will have as part of the treatment for leukemia). You will have a urine sample collected for routine tests. You will also have a bone mineral density test. This test measures the density of the bones in your spine, hip, and total body. The test is similar to having x-rays of your bones taken. You will be randomly assigned (as in the toss of a coin) to one of two treatment groups. Participants in the first group will be given risedronate (once per week), vitamin D (once per day), and calcium (once per day). All three medications are pills and will be taken by mouth. Participants in the second group will be given placebo (once per week), vitamin D (once per day), and calcium (once per day). All three medications are pills and will be taken by mouth. A placebo is a substance that looks like the study drug but has no active ingredients. Neither you nor your doctor will know to which group you are assigned. However, if it is needed for your care, the information will be given to your doctor. Participants in both groups will continue to receive chemotherapy during this study as scheduled. During chemotherapy, you will have around 1 tablespoon of blood drawn every 1-2 weeks for routine blood tests (as part of the standard of care for your treatment of leukemia). For this study, you will have urine samples collected and repeat bone mineral density tests 6 months, 12 months, 18 months, and 24 months after starting the study drug (or placebo). If you develop intolerable side effects from the risedronate you will be taken off the study. This is an investigational study. Risedronate is FDA approved and commercially available. Up to 80 eligible patients will take part in this study. All will be enrolled at M. D. Anderson.

Official Title
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A Randomized, Double Blinded Study of Actonel for the Prevention of Bone Loss in Patients Receiving High Dose Corticosteroids for the Treatment of Acute Lymphocytic Leukemia (ALL) and Lymphoblastic Lymphoma (LL)

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: Actonel (Risedronate)
* Dietary Supplement: Calcium
* Dietary Supplement: Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than or equal to 18 years Newly diagnosed ALL or LL receiving chemotherapy with augmented BFM, Hyper-CVAD or any variant of hyper-CVAD. Female patients of childbearing potential (i.e. no hysterectomy, no loss of menses for 12 consecutive months), must be willing to use contraception. Negative pregnancy test in female patients. Patients must be enrolled within 6 weeks of starting induction chemotherapy. Exclusion Criteria: Hypocalcemia of less than 8.4 (corrected to account for the albumin level, [see Appendix E for formula]) Hypersensitivity to risedronate or other bisphosphonates Inability to sit or stand upright for at least 30 minutes Bone density T-score of -2.5 S.D or less. Renal insufficiency (calculated creatinine clearance <30cc/min,[see Appendix F for formula]) Patients with a 25-hydroxyvitamin D concentration of less than 20 ng/ml and evidence of osteomalacia (low ionized calcium and high intact PTH). Concomitant use of bisphosphonates, calcitonin, anabolic steroids, or fluoride. Corrected calcium above 10.2, due to a cause not related to leukemia/lymphoma (i.e. hyperparathyroidism, multiple myeloma).

Ages Eligible for Study
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Minimum Age: 18 Years

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Actonel<br>Actonel (Risedronate) + Vitamin D + Calcium | Drug: Actonel (Risedronate)<br>* 35 mg (pill) by mouth weekly<br>* Other names: Risedronate Sodium;Dietary Supplement: Calcium<br>* 500 mg by mouth twice a day for a total of 24 months.<br>Dietary Supplement: Vitamin D<br>* 400 IU by mouth twice a day for a total of 24 months.<br>|
| Placebo Comparator: Placebo<br>Placebo + Vitamin D + Calcium | Dietary Supplement: Calcium<br>* 500 mg by mouth twice a day for a total of 24 months.<br>Dietary Supplement: Vitamin D<br>* 400 IU by mouth twice a day for a total of 24 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | bone mineral density (BMD) Mean percent Change in Bone Density from Baseline to 6 months. | 6 months | 
| Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | bone mineral density (BMD) Mean percent Change in Bone Density from Baseline to 12 months | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Lymphoma, Acute Lymphocytic Leukemia, Lymphoblastic Lymphoma, Actonel, Risedronate, Bone Loss, Osteoporosis