Prevention of Osteoporosis in Bone Marrow Transplantation (BMT) Patients
Condition: Hematological Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Ibandronate; Vitamin Supplements
Intervention description: Infusion of 3 mg by vein over 15 to 30 seconds for 4 doses at 3-6 weeks after transplant, and at Months 3, 6, and 9 after the transplant.; Calcium 500 mg by mouth everyday for 12 months
Vitamin D 400 units by mouth 2 times a day for 12 months
Intervention MeSH terms: Ibandronic Acid
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Blood Cancer; Calcium; Vitamin D; Ibandronate; Boniva; Hematological Malignancies; Bone Marrow Transplantation; BMT; Osteoporosis; Bone Loss; Allogeneic Bone Marrow Transplantation

Summary:

      The goal of this clinical research study is to see if ibandronate can help to slow the rate
      of bone loss that may occur in patients who have received a bone marrow transplant for blood
      cancer.

      This study plans to address the following hypotheses:

        1. The addition of Ibandronate initiated immediately after the transplantation will prevent
           bone loss in patients undergoing allogenic bone marrow transplantation (BMT) with
           underlying hematologic malignancies or hematologic disorders.

        2. BMT patients who require prolonged steroid and other immunosuppressive treatment for
           Graft versus Host Diseases(GVHD) have a higher rate of bone loss, which can be prevented
           or attenuated by Ibandronate.

      Specific objectives to test these hypotheses are:

        1. Primary Objective:

           1. To prospectively compare the bone mineral density changes of lumbar spine, femoral
           neck and total hip between patients randomly assigned to ibandronate and control group
           over 12 months post bone marrow transplantation at the University of Texas MD Anderson
           Cancer Center.

        2. Secondary Objectives:

             1. To measure and compare the accumulated level of steroid used in both treatment and
                control groups.

             2. To collect and compare the level of serum C-terminal telopeptide (CTX) in both
                treatment and control groups to monitor the bone turnover rate for the duration of
                the study.

             3. To conduct a cost-effectiveness analysis of participating patients for both
                outcomes on bone mineral density (measured data) and skeletal-related events
                (modeled data).

             4. To record incidence of bone fractures and the graft rate in both treatment and
                control groups.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age greater than or equal to 18 years.

          2. Patients with the diagnosis of hematologic malignancies or hematological disorders,
             who are immediately post- allogeneic bone marrow transplantation.

          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 premenopausal patients.

          5. Patients with GVHD or infections can be entered only if they respond to treatment and
             become controlled.

          6. Dental considerations: patients with negative dental screening for jaw osteonecrosis
             0-3 months prior to their transplant and patients that do not have a plan for tooth
             extraction in the near future.

        Exclusion Criteria:

          1. Patients with documented relapsed malignancy or recurrence of the original
             hematological disorder after the transplant, uncontrolled acute GVHD, or uncontrolled
             infection.

          2. Patients with hypocalcemia of less than 8.4 (corrected to account for the albumin
             level).

          3. Patients with hypercalcemia >12.2, due to a cause not related to their hematological
             malignancy or hematological disorder (i.e. hyperparathyroidism, multiple myeloma).

          4. Hypersensitivity to Ibandronate or other bisphosphonates.

          5. Pre-existing osteoporosis, defined as a bone density T-score of -2.5 S.D. or less.

          6. Renal insufficiency (calculated creatinine clearance < 30 ml/min).

          7. Patients already on bisphosphonates (over the past two years), calcitonin, anabolic
             steroids, or daily oral fluoride supplement.

          8. Myeloma patients who have previously been on bisphosphonates over the past two years
             and/or have active bone lesions.

          9. If corrected calcium is above 10.3 and the immunoreactive parathyroid hormone (iPTH)
             is elevated or normal, the patient will be excluded from the study.

         10. Patients with a 25-hydroxyvitamin D concentration <20 ng/ml and evidence of
             osteomalacia (low ionized calcium and elevated intact PTH).

         11. Dental considerations: Patients with recent tooth extraction with signs of incomplete
             healing or significant infection will be excluded.