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

NCT03925532 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: I 78618NCI-2019-01921
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

Allogeneic Hematopoietic Stem Cell Transplantation Recipient; Osteopenia; Osteoporosis

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (3)

• Mean Lumbar Spine Percent Change in BMD

  Baseline up to 100 days post-HSCT

• Frequency of Bone Fractures

  Up to 1 year post-HSCT

• Number of Participants That Experienced Any AE

  Up to 30 days

Study Arms (1)

Supportive Care (denosumab)

EXPERIMENTAL

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

Interventions

Denosumab BIOLOGICAL

Given SC

Also known as: AMG 162, AMG-162, Prolia, Xgeva

Supportive Care (denosumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• Amgen: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Bone Diseases, Metabolic; Osteoporosis

Interventions

Denosumab

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

The targeted sample size was n=114, with n=30 the primary analysis is underpowered. Potential reversal of bone loss might occur over a longer period of time.

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

adrienne.groman@roswellpark.org

7168451300

Study Officials

• Philip L McCarthy

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2019
• First Posted: April 24, 2019
• Study Start: December 19, 2019
• Primary Completion: November 16, 2022
• Study Completion: November 16, 2022
• Last Updated: March 13, 2024
• Results First Posted: March 13, 2024

Record last verified: 2024-03

Locations

US (2)