Clinical trial NCT03925532: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allogeneic Hematopoietic Stem Cell Transplantation Recipient
Osteopenia
Osteoporosis
Lead sponsor: Roswell Park Cancer Institute
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2019-04-24
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

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

Primary outcomes:
measure: Mean Total Hip Percent Change in Bone Mineral Density (BMD)
timeFrame: At baseline and 465 days post-HSCT
measure: Slope in Hip Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual
timeFrame: From the time of enrollment up to 465 days post-HSCT
measure: Mean Lumbar Spine Percent Change in Bone Mineral Density (BMD)
timeFrame: At baseline and 465 days post-HSCT
measure: Mean Total Hip Percent Change in Bone Mineral Density (BMD)
timeFrame: At baseline, at time of enrollment (day 100 post-hematopoietic stem cell transplantation [HSCT])
measure: Slope in Lumbar Spine Bone Mineral Density (g/cm^2 Per Day) Regressed on Time in Dual
timeFrame: From the time of enrollment up to 465 days post-HSCT
Secondary outcomes:
measure: Mean Lumbar Spine Percent Change in BMD
timeFrame: Baseline up to 100 days post-HSCT
measure: Frequency of Bone Fractures
timeFrame: Up to 1 year post-HSCT
measure: Number of Participants That Experienced Any AE
timeFrame: Up to 30 days
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
affiliation: Roswell Park Cancer Institute
name: Philip L McCarthy
role: PRINCIPAL_INVESTIGATOR
References: