Relapsed or Plateau-Phase Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Relapsed, Plateau-Phase
Brief summary
The purpose of this study is to determine if denosumab is effective in the treatment of relapsed or plateau-phase multiple myeloma.
Detailed description
Patients who have relapsed myeloma have failed treatment regimens and have had disease progression following their last treatment regimen. Despite newer salvage therapies, their treatment options are limited and may include best supportive care and investigational therapy. Patients with plateau-phase myeloma have a stabilized serum M-protein level without further tumor regression despite continued treatment. Recent evidence suggests that their prognosis might improve with further reduction in serum M-protein or prolongation of time to disease progression (TTP). These patients are candidates for investigational agents that could further reduce tumor burden or increase TTP.
Interventions
DRUGDENOSUMAB
120 mg administered subcutaneously on study days 1, 8, 15, and 29 and every 28 days thereafter. Each dose will be administered in two separate injections of 60 mg (1.0 mL) each.
Sponsors
Amgen
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
* age ≥ 18 years * clinical diagnosis of relapsed or plateau-phase multiple myeloma * measurable disease (\>0.5 g/dL) as determined by special blood tests * ECOG 0 or 1
Exclusion criteria
* newly diagnosed myeloma * non-secretory myeloma * plasma cell leukemia or plasma cell dyscrasia with POEMS syndrome * prior allogeneic stem cell transplant * administration of oral or IV bisphosphonates within 2 weeks of enrollment to study Other criteria also apply.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response or Partial Response Based on M-Protein Assessments Only | Up to 18 months | Complete response or partial response based on serum M-Protein assessments. Complete response is defined as absence of original M-protein in serum by immunofixation, and partial response is defined as ≥ 50% reduction from baseline in serum M-protein, both maintained for a minimum of 6 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response, Partial Response or Minimal Response Based on M-Protein Assessments Only | Up to 18 months | Complete response, partial response or minimal response based on serum M-protein assessments. Complete and partial responses are as defined for the primary outcome measure. Minimal response is defined as 25 to 49% reduction from baseline in serum M-protein level, maintained for a minimum of 6 weeks. |
| Complete Response Based on M-Protein Assessments Only | Up to 18 months | Complete response based on M-protein assessments, as defined for the primary outcome measure. |
Participant flow
Recruitment details
Participants were enrolled from 13 February 2006 through 8 December 2006
Participants by arm
| Arm | Count |
|---|---|
| Denosumab 120 mg Q4W - Plateau-Phase Open-label denosumab 120 mg by subcutaneous injection on day 1 of each 28-day cycle with additional loading doses on days 8 and 15 of cycle 1 in participants with plateau-phase multiple myeloma | 43 |
| Denosumab 120 mg Q4W - Relapsed Open-label denosumab 120 mg by subcutaneous injection on day 1 of each 28-day cycle with additional loading doses on days 8 and 15 of cycle 1 in participants with relapsed multiple myeloma | 53 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Disease progression | 19 | 36 |
| Overall Study | Ongoing | 17 | 3 |
| Overall Study | Other | 3 | 0 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Requirement for alternative therapy | 0 | 4 |
| Overall Study | Withdrawal by Subject | 2 | 6 |
Baseline characteristics
| Characteristic | Denosumab 120 mg Q4W - Plateau-Phase | Denosumab 120 mg Q4W - Relapsed | Total |
|---|---|---|---|
| Age, Continuous | 61.1 Years STANDARD_DEVIATION 11.4 | 62.9 Years STANDARD_DEVIATION 9.2 | 62.1 Years STANDARD_DEVIATION 10.2 |
| Race/Ethnicity, Customized African American | 4 Participants | 7 Participants | 11 Participants |
| Race/Ethnicity, Customized Caucasian | 35 Participants | 39 Participants | 74 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Female | 26 Participants | 13 Participants | 39 Participants |
| Sex: Female, Male Male | 17 Participants | 40 Participants | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 38 / 53 | 32 / 42 |
| serious Total, serious adverse events | 14 / 53 | 6 / 42 |
Outcome results
Primary
Complete Response or Partial Response Based on M-Protein Assessments Only
Complete response or partial response based on serum M-Protein assessments. Complete response is defined as absence of original M-protein in serum by immunofixation, and partial response is defined as ≥ 50% reduction from baseline in serum M-protein, both maintained for a minimum of 6 weeks.
Time frame: Up to 18 months
Population: All participants who completed the first cycle of treatment with denosumab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 120 mg Q4W - Plateau-Phase | Complete Response or Partial Response Based on M-Protein Assessments Only | 0 Participants |
| Denosumab 120 mg Q4W - Relapsed | Complete Response or Partial Response Based on M-Protein Assessments Only | 0 Participants |
Secondary
Complete Response Based on M-Protein Assessments Only
Complete response based on M-protein assessments, as defined for the primary outcome measure.
Time frame: Up to 18 months
Population: All participants who completed the first cycle of treatment with denosumab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 120 mg Q4W - Plateau-Phase | Complete Response Based on M-Protein Assessments Only | 0 Participants |
| Denosumab 120 mg Q4W - Relapsed | Complete Response Based on M-Protein Assessments Only | 0 Participants |
Secondary
Complete Response, Partial Response or Minimal Response Based on M-Protein Assessments Only
Complete response, partial response or minimal response based on serum M-protein assessments. Complete and partial responses are as defined for the primary outcome measure. Minimal response is defined as 25 to 49% reduction from baseline in serum M-protein level, maintained for a minimum of 6 weeks.
Time frame: Up to 18 months
Population: All participants who completed the first cycle of treatment with denosumab
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Denosumab 120 mg Q4W - Plateau-Phase | Complete Response, Partial Response or Minimal Response Based on M-Protein Assessments Only | 0 Participants |
| Denosumab 120 mg Q4W - Relapsed | Complete Response, Partial Response or Minimal Response Based on M-Protein Assessments Only | 0 Participants |