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

Primary Purpose

Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Osteopenia, Osteoporosis

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Denosumab

About this trial

This is an interventional supportive care trial for Allogeneic Hematopoietic Stem Cell Transplantation Recipient

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Roswell Park Cancer Institute
Cleveland Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Supportive Care (denosumab)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

Frequency of bone fractures

Will be tabulated overall.

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.

Full Information

NCT ID

NCT03925532

First Posted

April 16, 2019

Last Updated

February 9, 2023

Sponsor

Roswell Park Cancer Institute

Collaborators

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT03925532

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2023

Overall Recruitment Status

Completed

Study Start Date

December 19, 2019 (Actual)

Primary Completion Date

November 16, 2022 (Actual)

Study Completion Date

November 16, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Roswell Park Cancer Institute

Collaborators

Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Allogeneic Hematopoietic Stem Cell Transplantation Recipient, Osteopenia, Osteoporosis

7. Study Design

Primary Purpose

Supportive Care

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Supportive Care (denosumab)

Arm Type

Experimental

Arm Description

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.

Intervention Type

Biological

Intervention Name(s)

Denosumab

Other Intervention Name(s)

AMG 162, AMG-162, Prolia, Xgeva

Intervention Description

Given SC

Primary Outcome Measure Information:

Title

Changes in bone mineral density (BMD)

Description

Time Frame

At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT]), and 465 days post-HSCT

Title

Slope in bone mineral density (g/cm^2) regressed on time in dual femur and lumbar spine (average of L1-L4)

Description

Time Frame

From the time of enrollment up to 465 days post-HSCT

Secondary Outcome Measure Information:

Title

Percent change in BMD

Description

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.

Time Frame

Baseline up to 465 days post-HSCT

Title

Frequency of bone fractures

Description

Will be tabulated overall.

Time Frame

Up to 1 year post-HSCT

Title

Incidence of adverse events

Description

Time Frame

Up to 30 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Philip L McCarthy

Organizational Affiliation

Roswell Park Cancer Institute

Official's Role

Principal Investigator

Facility Information:

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

Cleveland Clinic

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

12. IPD Sharing Statement

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

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