Denosumab in Treating Patients With Bone Loss Due to Donor Stem Cell Transplant

Study Overview
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Brief Summary
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This Phase II trial studies the side effects of denosumab and to see how well it works in treating patients with bone loss who have received a donor stem cell transplant. Patients receiving a donor stem cell transplant may experience accelerated bone loss and an increase risk of bone fractures, leading to a decrease in satisfaction and quality of life. A type of immunotherapy drug called denosumab binds to a protein called RANKL, which may help keep bone from breaking down.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the efficacy and safety of denosumab therapy for the treatment of bone loss in patients who have received an allogeneic hematopoietic stem cell transplant. OUTLINE: Patients receive 2 doses of denosumab subcutaneously (SC) between days 70-130 and days 250-310 after allogeneic hematopoietic stem cell transplant in the absence of disease progression or unacceptable toxicity. After completion of study treatment patients are followed up at 6 months.

Official Title
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A Phase II Multicenter, Single Arm, Open-Label Trial to Evaluate the Efficacy and Safety of Denosumab in Treatment of Post-Allogenic Hematopoietic Stem Cell Transplant Bone Loss

Conditions
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Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Osteopenia, Osteoporosis

Intervention / Treatment
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* Biological: Denosumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient has undergone an Allogeneic Hematopoietic Stem Cell Transplant The patient has completed a base line dual x-ray absorptiometry (DXA) scan =< 6 months prior to transplantation The patient has completed a post-transplant DXA scan at day 100 (+/- 30 days) or up to 6 months post transplantation The patient has completed and passed a dental clearance exam up to 6 months prior to transplant or 6 months after transplant Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) prior to study entry. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: The patient has a history of a hypersensitivity reaction to denosumab The patient has a history of osteonecrosis of the jaw The patient has predisposing risk factors for hypocalcemia including the following: Hypoparathyroidism Creatinine clearance (CrCl) < 30 mL/min Dialysis Malabsorption syndrome The patient has history of any bone fracture =< 30 days prior to denosumab therapy Pregnant or nursing female patients. The patient has clinically significant GVHD leading to hospitalization at the time of denosumab dose per prescriber discretion. The patient has clinically significant infection leading to hospitalization at the time of denosumab dose (excluding hospitalization due to complexity of treatment leading to inability to treat outpatient, ie. Foscarnet) per prescriber discretion The patient is unwilling or unable to follow protocol requirements The patient has any condition which in the investigator's opinion deems the participant an unsuitable candidate to receive study drug including relapsed malignancy

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: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supportive Care (denosumab)<br>Patients receive 2 doses of denosumab SC between days 70-130 and days 250-310 after allogeneic hematopoietic stem cell transplant in the absence of disease progression or unacceptable toxicity. | Biological: Denosumab<br>* Given SC<br>* Other names: Xgeva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in bone mineral density (BMD) | Day 100 dual x-ray absorptiometry (DXA) scan and day 465 DXA scan will be compared based on the percent change in BMD in the Total hip and/or lumbar spine in allogeneic HSCT patients who have experienced either at least 5% BMD loss between baseline (pre- HSCT) and day + 100 post-HSCT, or who have osteopenia or osteoporosis at either the pre-bone marrow transplant or day + 100 DXA scan. | At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT]), and 465 days post-HSCT | 
| Slope in bone mineral density (g/cm^2) regressed on time in dual femur and lumbar spine (average of L1-L4) | The analysis for both the femur and lumbar spine will consist of a regression model of the percent change from enrollment to 465 days post HSCT regressed on the enrollment BMD levels. The analysis model will be fit using Ordinary Least Square methods. A secondary model will include and expand upon a list of covariates to explore the effects of demographic, disease and treatment characteristics on BMD loss and effectiveness of denosumab using an analysis-of-covariance model. Both models will be tested at alpha = 0.05 (two-sided). Residual plots and other diagnostic methods will be used to evaluate compliance with model assumptions and goodness of fit. | From the time of enrollment up to 465 days post-HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in BMD | Will be compared between the pre-HSCT and the day 465 post-HSCT DXA scans for dual femur and/or lumbar spine (L1-L4). Will be tabulated overall. | Baseline up to 465 days post-HSCT | 
| Frequency of bone fractures | Will be tabulated overall. | Up to 1 year post-HSCT | 
| Incidence of adverse events | Including but not limited to the following: Injection/hypersensitivity related reactions; osteonecrosis of the jaw; graft versus host disease. Will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5 and tabulated by grade. | Up to 30 days |