Leukemia, Lymphoma
Conditions
Keywords
Leukemia, Lymphoma, Acute Lymphocytic Leukemia, Lymphoblastic Lymphoma, Actonel, Risedronate, Bone Loss, Osteoporosis
Brief summary
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
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.
Interventions
35 mg (pill) by mouth weekly
DIETARY_SUPPLEMENTCalcium
500 mg by mouth twice a day for a total of 24 months.
DIETARY_SUPPLEMENTVitamin D
400 IU by mouth twice a day for a total of 24 months.
Sponsors
Procter and Gamble
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age greater than or equal to 18 years 2. Newly diagnosed ALL or LL receiving chemotherapy with augmented BFM, Hyper-CVAD or any variant of hyper-CVAD. 3. Female patients of childbearing potential (i.e. no hysterectomy, no loss of menses for 12 consecutive months), must be willing to use contraception. 4. Negative pregnancy test in female patients. 5. Patients must be enrolled within 6 weeks of starting induction chemotherapy.
Exclusion criteria
1. Hypocalcemia of less than 8.4 (corrected to account for the albumin level, \[see Appendix E for formula\]) 2. Hypersensitivity to risedronate or other bisphosphonates 3. Inability to sit or stand upright for at least 30 minutes 4. Bone density T-score of -2.5 S.D or less. 5. Renal insufficiency (calculated creatinine clearance \<30cc/min,\[see Appendix F for formula\]) 6. Patients with a 25-hydroxyvitamin D concentration of less than 20 ng/ml and evidence of osteomalacia (low ionized calcium and high intact PTH). 7. Concomitant use of bisphosphonates, calcitonin, anabolic steroids, or fluoride. 8. Corrected calcium above 10.2, due to a cause not related to leukemia/lymphoma (i.e. hyperparathyroidism, multiple myeloma).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | 6 months | bone mineral density (BMD) Mean percent Change in Bone Density from Baseline to 6 months. |
| Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | 12 months | bone mineral density (BMD) Mean percent Change in Bone Density from Baseline to 12 months |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: February 06, 2004 to March 10, 2010. All participants were recruited at University of Texas (UT) MD Anderson Cancer Center.
Participants by arm
| Arm | Count |
|---|---|
| Actonel Actonel (Risedronate) + Vitamin D + Calcium
Actonel 35 mg orally weekly, Calcium 500 mg orally twice a day, and Vitamin D 400 IU orally twice a day for a total of 24 months. | 36 |
| Placebo Placebo + Vitamin D + Calcium
Placebo weekly, Calcium 500 mg orally twice a day, and Vitamin D 400 IU orally twice a day for a total of 24 months. | 36 |
| Total | 72 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Bone Marrow Transplant | 0 | 1 |
| Overall Study | Death | 3 | 1 |
| Overall Study | Failed to achieve complete response | 2 | 0 |
| Overall Study | Fracture | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Refused Treatment | 4 | 3 |
| Overall Study | Relapse | 3 | 0 |
| Overall Study | Too Ill to Continue | 0 | 1 |
Baseline characteristics
| Characteristic | Actonel | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 29 years | 36 years | 42 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 18 Participants | 35 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants | 37 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 34 Participants | 70 Participants | 36 Participants |
| Region of Enrollment United States | 36 participants | 72 participants | 36 participants |
| Sex: Female, Male Female | 12 Participants | 27 Participants | 15 Participants |
| Sex: Female, Male Male | 24 Participants | 45 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 36 | 1 / 36 |
| other Total, other adverse events | 0 / 36 | 0 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
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
Time frame: 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actonel | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | Lumbar Spine 12 Months | -0.6 percentage of change | Standard Deviation 0.05 |
| Actonel | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | Right Hip 12 Months | -4.8 percentage of change | Standard Deviation 0.05 |
| Actonel | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | Left Hip 12 Months | -4.1 percentage of change | Standard Deviation 0.05 |
| Placebo | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | Lumbar Spine 12 Months | -5 percentage of change | Standard Deviation 0.05 |
| Placebo | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | Right Hip 12 Months | -5.8 percentage of change | Standard Deviation 0.05 |
| Placebo | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months | Left Hip 12 Months | -7 percentage of change | Standard Deviation 0.03 |
Primary
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.
Time frame: 6 months
Population: Of 72 randomized, 22 participants in risedronate \& 29 in placebo had at least a 6-month follow-up bone mineral density and were considered evaluable for the primary endpoint. Only 12/22 patients (55%) in risedronate and 7/29 patients (24%) in the placebo arm had 12 month DXA scan performed, mostly due to significant decreases in bone density.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Actonel | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | Lumbar Spine 6 Months | -2.4 Percent of change | Standard Deviation 0.05 |
| Actonel | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | Right Hip 6 Months | -7.6 Percent of change | Standard Deviation 0.06 |
| Actonel | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | Left Hip 6 Months | -8.2 Percent of change | Standard Deviation 0.06 |
| Placebo | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | Lumbar Spine 6 Months | -3.5 Percent of change | Standard Deviation 0.04 |
| Placebo | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | Right Hip 6 Months | -11 Percent of change | Standard Deviation 0.06 |
| Placebo | Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at the 6 Months | Left Hip 6 Months | -11 Percent of change | Standard Deviation 0.06 |