A Study of Actonel for the Prevention of Bone Loss

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00452439
• Collaborator: Procter and Gamble (Industry)
• Enrollment: 72
• Location: 1
• Arms: 2
• Duration (Months): 126
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Lymphoma	Drug: Actonel (Risedronate); Dietary Supplement: Calcium; Dietary Supplement: Vitamin D	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Study Start Date: Feb 1, 2004
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Aug 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Procter and Gamble

Investigators

• Principal Investigator: Maria E. Cabanillas, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00452439
• Other Study ID Numbers: ID03-0124; NCI-2010-01997
• First Posted: Mar 27, 2007
• Last Update Posted: Dec 28, 2020
• Last Verified: Dec 1, 2020

• Keywords provided by M.D. Anderson Cancer Center: Leukemia; Lymphoma; Acute Lymphocytic Leukemia; Lymphoblastic Lymphoma; Actonel; Risedronate; Bone Loss; Osteoporosis
• Additional relevant MeSH terms: Lymphoma; Leukemia; Vitamin D; Risedronic Acid; Etidronic Acid; Calcium

Study Results

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.

Arm/Group Title	Actonel	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	36	36
COMPLETED	22	29
NOT COMPLETED	14	7

Baseline Characteristics

Arm/Group Title	Actonel	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	36	36	72
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	29	42	36
Sex: Female, Male (Count of Participants)
Female	12 33.3%	15 41.7%	27 37.5%
Male	24 66.7%	21 58.3%	45 62.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 50%	17 47.2%	35 48.6%
Not Hispanic or Latino	18 50%	19 52.8%	37 51.4%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 5.6%	0 0%	2 2.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	34 94.4%	36 100%	70 97.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	36 100%	36 100%	72 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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/Group Title	Actonel	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	29
Lumbar Spine 6 Months	-2.4 (0.05)	-3.5 (0.04)
Right Hip 6 Months	-7.6 (0.06)	-11 (0.06)
Left Hip 6 Months	-8.2 (0.06)	-11 (0.06)

2. Primary Outcome

Title	Bone Loss Reduction: Mean Percent Changes in BMD for Each Treatment Arm at 12 Months
Description	bone mineral density (BMD) Mean percent Change in Bone Density from Baseline to 12 months
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Actonel	Placebo
Arm/Group Description	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.	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.
Measure Participants	12	7
Lumbar Spine 12 Months	-0.6 (0.05)	-5 (0.05)
Right Hip 12 Months	-4.8 (0.05)	-5.8 (0.05)
Left Hip 12 Months	-4.1 (0.05)	-7 (0.03)

Adverse Events

Time Frame	Up to 6 years
Arm/Group Title	Actonel		Placebo
Arm/Group Description	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.		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.
All Cause Mortality
	Actonel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/36 (8.3%)		1/36 (2.8%)
Serious Adverse Events
	Actonel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)
Other (Not Including Serious) Adverse Events
	Actonel		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/36 (0%)		0/36 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.