Multiple Myeloma
Conditions
Keywords
aminobisphosphonates
Brief summary
The purpose of this research study is to define the time a molecule in the participants bones called NTX begins to rise after receiving treatment with bisphosphonates. NTX is measured in the urine to determine the rate of bone breakdown. Tracking this marker may help identify a more optimal dosing schedule of bisphosphonate therapy. Bisphosphonate drugs like zoledronic acid, which will be used in this study, are used to reduce pain and bone fractures in people with multiple myeloma. There is some laboratory data to suggest that they may work against myeloma. Participants will have already undergone bisphosphonate therapy and may have received zoledronic acid as treatment. Typically these agents are continued indefinitely. Due to concerns of their long-term side effects we are looking at alternate strategies for reducing the frequency of these agents.
Detailed description
* Each participant will receive a single dose of zoledronic acid intravenously after the screening procedures. * Participants will then return to the clinic once every month for 6 months and have the following tests and procedures performed: Medical history update; physical exam; ECOG (Eastern Cooperative Oncology Group) Performance Status; blood tests; and urine tests. * After 6 months there will be an end of study visit, where the following procedures will take place: medical history update; bone marrow aspirate and biopsy; skeletal survey.
Interventions
DRUGZoledronic acid
4mg IV over at least 15 minutes or corrected for creatinine clearance x 1
Sponsors
Brigham and Women's Hospital
Dana-Farber Cancer Institute
American Society of Clinical Oncology
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women 18 years of age or older * Confirmed diagnosis of multiple myeloma(MM) by Durie and Dalmon staging criteria on IV bisphosphonate therapy with either pamidronate or zoledronic acid for 8-12 months * MM patients in either CR (complete response) or PR (partial response) by EBMT criteria * ECOG Performance Status of 0-2
Exclusion criteria
* MM patients on active anti-MM therapy (maintenance regimens allowed) * Renal failure with serum creatinine \>2mg/dL and/or creatinine clearance of \<30ml/min * Relapsed, refractory or progressive disease * Any condition or situation that, in the opinion of the investigator, may put the subject at significant risk, confound the results of the study, or interfere significantly with the subject's participation in the study * Hypersensitivity or any contraindication to a single dose of zoledronic acid
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Urinary NTX Levels Less Than or Equal to 50nmol/mmol Cr | 6 months | Number of participants with urinary NTX levels less than or equal to 50 nmol/mmol creatinine (Cr) for the duration of study followup, following a single dose Zoledronic Acid (Zoledronate) 4mg IV over at least 15 minutes (or dose corrected for creatinine clearance x1). Dose administration was followed by Aminobisphosphonates (aBP) treatment cessation during study period. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zoledronic Acid Single dose Zoledronic Acid (Zoledronate) 4mg IV over at least 15 minutes (or dose corrected for creatinine clearance x1) followed by Aminobisphosphonates (aBP) cessation during study period | 29 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Clinical Disease Progression | 1 |
Baseline characteristics
| Characteristic | Zoledronic Acid |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants |
| Age, Continuous | 60 years |
| Autologous Transplant No | 16 Participants |
| Autologous Transplant Yes | 13 Participants |
| Bone Lesions ≤ 3 bone lesions | 9 participants |
| Bone Lesions > 3 bone lesions | 20 participants |
| ISS Stage Stage I | 11 participants |
| ISS Stage Stage II | 9 participants |
| ISS Stage Stage III | 9 participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 16 Participants |
| Therapy Bortezomib + lenalidomide | 14 participants |
| Therapy Bortezomib + Other | 10 participants |
| Therapy Other | 5 participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
Primary
Number of Participants With Urinary NTX Levels Less Than or Equal to 50nmol/mmol Cr
Number of participants with urinary NTX levels less than or equal to 50 nmol/mmol creatinine (Cr) for the duration of study followup, following a single dose Zoledronic Acid (Zoledronate) 4mg IV over at least 15 minutes (or dose corrected for creatinine clearance x1). Dose administration was followed by Aminobisphosphonates (aBP) treatment cessation during study period.
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zoledronic Acid | Number of Participants With Urinary NTX Levels Less Than or Equal to 50nmol/mmol Cr | NTX level ≤ 50 nmol/mmol Cr | 28 Participants |
| Zoledronic Acid | Number of Participants With Urinary NTX Levels Less Than or Equal to 50nmol/mmol Cr | NTX level > 50 nmol/mmol Cr | 1 Participants |
Comparison: Paired t-tests were used to compare differences of NTX cytokine levels at study entry versus end-of-study.p-value: <0.05t-test, 1 sided