Denosumab in Treating Patients with Multiple Myeloma with Kidney Insufficiency
Multiple Myeloma
Plasma cell neoplasm
18 Years and older, Male and Female
15-571 (primary)
NCI-2016-01375
Summary
This phase II trial studies how well denosumab works in treating patients with multiple myeloma with kidney insufficiency. Bone disease is a common and serious complication of multiple myeloma. Standard therapy includes the use of medications that strengthen the bones to lower the risk of bone complications called bisphosphonates. A limitation of current therapies is that they cannot be administered in patients with severe kidney dysfunction which is another common complication in multiple myeloma. Denosumab is a monoclonal protein against RANK ligand. It works to prevent bone loss by blocking a certain receptor in the body to decrease bone breakdown. It is believed to be safe to use in patients with kidney dysfunction.
Objectives
PRIMARY OBJECTIVE:
I. To assess the effect of denosumab 120 mg every 4 weeks (Q4W) on serum c-terminal telopeptide (sCTX) levels in multiple myeloma (MM) patients with renal insufficiency, defined as a creatinine clearance (CrCl) < 30 mL/min.
SECONDARY OBJECTIVES:
I. To assess the safety and tolerability of denosumab in MM patients with renal insufficiency.
II. To assess the incidence of hypocalcemia in patients with renal insufficiency receiving denosumab.
III. To assess the effect of denosumab on bone mineral density.
IV. To assess the effect of denosumab on urinary n-terminal telopeptide (uNTX).
V. To evaluate the proportions of subjects who have a documented skeletal-related event (SRE).
EXPLORATORY OBJECTIVE:
I. To assess the effect of denosumab on bone turnover markers which may include osteocalcin and procollagen 1 n-terminal propeptide (P1NP).
OUTLINE:
Patients receive denosumab subcutaneously (SC) on day 1. Treatment repeats every 4 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks for 2 years.
Eligibility
- Subjects must have documented multiple myeloma as defined by one or more of the criteria below:
* Clonal bone marrow plasma cells >= 10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following calcium, renal failure, anemia, bone lesions (CRAB) features and myeloma-defining events (MDEs)
* Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:
** Hypercalcemia: serum calcium > 0.25 mmol/L (> 1 mg/dL) higher than the upper limit of normal or > 2.75 mmol/L (> 11 mg/dL)
** Renal insufficiency: creatinine clearance < 40 mL per minute or serum creatinine > 177 umol/L (> 2 mg/dL)
** Anemia: hemoglobin value of > 20 g/L below the lowest limit of normal, or a hemoglobin value < 100 g/L
** Bone lesions: one or more osteolytic lesion on skeletal radiography, computed tomography (CT), or positron emission tomography (PET)/CT
* Any one or more of the following biomarkers of malignancy (MDEs)
** 60% or greater clonal plasma cells on bone marrow examination
** Serum involved / uninvolved free light chain ratio of 100 or greater, provided the absolute level of the involved free light chain is at least 100 mg/L (a patient’s “involved” free light chain – either kappa or lambda – is the one that is above the normal reference range; the uninvolved light chain is the one that typically is in, or below, the normal range)
** More than one focal lesion on magnetic resonance imaging (MRI) that is at least 5 mm or greater in size
- Creatinine clearance < 30 mL/min, not eligible for bisphosphonate; estimated glomerular filtration rate will be calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and/or the Cockcroft-Gault equation
- Serum calcium or albumin-adjusted serum calcium >= 2.1 mmol/L (8.4 mg/dL) and =< 2.9 mmol/L (11.5 mg/dL) (reference range 8.5-10.8 mg/dL)
- Able to tolerate daily supplementation of calcium and vitamin D
- Must have a vitamin D level >= 30 ng/mL after repletion
- Total bilirubin =< 2.0 x institutional upper limit of normal (ULN)
- Aspartate aminotransferases (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) =< 2.5 x institutional ULN
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional ULN
- Plan to receive anti-myeloma therapies
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy greater than 6 months
- Subjects with reproductive potential must be willing to use, in combination with his/her partner, 2 highly effective methods of effective contraception or practice sexual abstinence throughout the study and continue for 5 months after the study duration; subjects who are surgically sterile (e.g. history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy) are not required to use additional contraceptive measures
- Ability to understand and the willingness to sign a written informed consent document
Treatment Sites in Georgia
**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts...
Click here to learn more about clinical trials.