Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Osteopenia, Osteoporosis
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALDenosumab
Given SC
Sponsors
Amgen
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Total Hip Percent Change in Bone Mineral Density (BMD) | At baseline and 465 days post-HSCT | Day 0 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 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. |
| Slope in Hip Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual | From the time of enrollment up to 465 days post-HSCT | Parameter estimate of the slope of the regression model of the hip bone mineral density change at day 465 post-HSCT regressed on the enrollment BMD levels. |
| Mean Lumbar Spine Percent Change in Bone Mineral Density (BMD) | At baseline and 465 days post-HSCT | Day 0 dual x-ray absorptiometry (DXA) scan and day 465 DXA scan will be compared based on the percent change in BMD in 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. |
| Slope in Lumbar Spine Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual | From the time of enrollment up to 465 days post-HSCT | Parameter estimate of the slope of the regression model of the lumbar spine bone mineral density change at day 465 post-HSCT regressed on the enrollment BMD levels. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Bone Fractures | Up to 1 year post-HSCT | The number of participants with bone fractures tabulated overall |
| Number of Participants That Experienced Any AE | Up to 30 days | 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. |
| Mean Lumbar Spine Percent Change in BMD | Baseline up to 100 days post-HSCT | Day 100 dual x-ray absorptiometry (DXA) scan will be compared based on the percent change in BMD in the 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Supportive Care (Denosumab) 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.
Denosumab: Given SC | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Supportive Care (Denosumab) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants |
| Age, Continuous | 60.38 years STANDARD_DEVIATION 9.65 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 26 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 7 / 30 |
| other Total, other adverse events | 2 / 30 |
| serious Total, serious adverse events | 5 / 30 |
Outcome results
Primary
Mean Lumbar Spine Percent Change in Bone Mineral Density (BMD)
Day 0 dual x-ray absorptiometry (DXA) scan and day 465 DXA scan will be compared based on the percent change in BMD in 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.
Time frame: At baseline and 465 days post-HSCT
Population: All treated and eligible patients that had measure taken at day 0 and day 465
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Supportive Care (Denosumab) | Mean Lumbar Spine Percent Change in Bone Mineral Density (BMD) | 0.77 percentage change | Standard Deviation 5.85 |
Primary
Mean Total Hip Percent Change in Bone Mineral Density (BMD)
Day 0 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 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.
Time frame: At baseline and 465 days post-HSCT
Population: All treated and eligible patients that had measures at day 0 and day 465
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Supportive Care (Denosumab) | Mean Total Hip Percent Change in Bone Mineral Density (BMD) | -4.28 percent change | Standard Deviation 7.13 |
Primary
Mean Total Hip Percent Change in Bone Mineral Density (BMD)
Day 100 dual x-ray absorptiometry (DXA) scan will be compared based on the percent change in BMD in the Total hip 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.
Time frame: At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT])
Population: All treated and eligible patients with measure at day 0 and day 100
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Supportive Care (Denosumab) | Mean Total Hip Percent Change in Bone Mineral Density (BMD) | -7.61 percentage change | Standard Deviation 4.54 |
Primary
Slope in Hip Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual
Parameter estimate of the slope of the regression model of the hip bone mineral density change at day 465 post-HSCT regressed on the enrollment BMD levels.
Time frame: From the time of enrollment up to 465 days post-HSCT
Population: All treated and eligible patients with measures collected
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Supportive Care (Denosumab) | Slope in Hip Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual | 0.04026 g/cm^2 per day |
Primary
Slope in Lumbar Spine Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual
Parameter estimate of the slope of the regression model of the lumbar spine bone mineral density change at day 465 post-HSCT regressed on the enrollment BMD levels.
Time frame: From the time of enrollment up to 465 days post-HSCT
Population: All treated and eligible patients with measures collected
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Supportive Care (Denosumab) | Slope in Lumbar Spine Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual | -0.09690 g/cm^2 per day |
Secondary
Frequency of Bone Fractures
The number of participants with bone fractures tabulated overall
Time frame: Up to 1 year post-HSCT
Population: All treated and eligible patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Denosumab) | Frequency of Bone Fractures | 0 Participants |
Secondary
Mean Lumbar Spine Percent Change in BMD
Day 100 dual x-ray absorptiometry (DXA) scan will be compared based on the percent change in BMD in the 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.
Time frame: Baseline up to 100 days post-HSCT
Population: All treated and eligible patients with measures at day 0 and day 100
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Supportive Care (Denosumab) | Mean Lumbar Spine Percent Change in BMD | -4.04 percentage change | Standard Deviation 5.46 |
Secondary
Number of Participants That Experienced Any AE
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.
Time frame: Up to 30 days
Population: All treated and eligible patients
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Supportive Care (Denosumab) | Number of Participants That Experienced Any AE | 7 Participants |