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

Phase 2

Completed

Conditions: Allogeneic Hematopoietic Stem Cell Transplantation Recipient
Osteoporosis
Osteopenia

Interventions: Biological: Denosumab

Registration Number: NCT03925532

Lead Sponsor: Roswell Park Cancer Institute

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Supportive Care (denosumab)	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.

Primary Outcome Measures

Name	Time	Method
Mean Total Hip Percent Change in Bone Mineral Density (BMD)	At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT])	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.
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.
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.
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.

Secondary Outcome Measures

Name	Time	Method
Frequency of Bone Fractures	Up to 1 year post-HSCT	The number of participants with bone fractures tabulated overall
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.
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.

Trial Locations

Locations (2): Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States