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

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

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.

Study Overview

• Status: Completed
• Conditions: Osteoporosis; Osteopenia; Allogeneic Hematopoietic Stem Cell Transplantation Recipient
• Intervention / Treatment: Biological: Denosumab

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Denosumab; Given SC; Other Names: Prolia; AMG 162; AMG-162; Xgeva

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At baseline and 465 days post-HSCT
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.	From the time of enrollment up to 465 days post-HSCT
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.	At baseline and 465 days post-HSCT
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.	At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT])
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.	From the time of enrollment up to 465 days post-HSCT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline up to 100 days post-HSCT
Frequency of Bone Fractures	The number of participants with bone fractures tabulated overall	Up to 1 year post-HSCT
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.	Up to 30 days

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Collaborators: Amgen
• Investigators: Principal Investigator: Philip L McCarthy, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2019
• Primary Completion (Actual): November 16, 2022
• Study Completion (Actual): November 16, 2022

Study Registration Dates

• First Submitted: April 16, 2019
• First Submitted That Met QC Criteria: April 22, 2019
• First Posted (Actual): April 24, 2019

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Osteoporosis; Bone Diseases, Metabolic; Physiological Effects of Drugs; Bone Density Conservation Agents; Denosumab
• Other Study ID Numbers: I 78618 (Other Identifier: Roswell Park Cancer Institute); NCI-2019-01921 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes