Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Untreated multiple myeloma, Bortezomib, VELCADE, Cyclophosphamide, Dexamethasone, Chemotherapy, Remission therapy, Induction therapy, Stem Cell Transplantation
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of bortezomib in combination with a standard regimen of cyclophosphamide and dexamethasone.
Detailed description
This is open-label (both the participant and the investigator know what treatment participants will receive), prospective (participants are identified and then followed forward in time for the outcome of the study), multi-centre, and non-randomized (participants are assigned to different treatment groups by the investigator) study. The study will be conducted into 2 parts (Part 1 and Part 2). Approximately 400 participants will be enrolled (30 in Part 1 and 370 in Part 2). In Part 1 the optimum dose of cyclophosphamide will be evaluated and in Part 2 the selected dose of cyclophosphamide from Part 1 will be administered. Part 2 will include a screening period of a maximum of 14 days followed by chemotherapy (bortezomib, cyclophosphamide, and dexamethasone) of a maximum of three 21-day cycles. Safety will be evaluated by the assessment of adverse events, vital signs, physical examination, electrocardiogram, and clinical laboratory tests which will be monitored throughout the study.
Interventions
DRUGCyclophosphamide
In Part 1, cyclophosphamide with dose ranging from 900 to 1500 mg will be administered intravenously on Day 1 of each 21 day cycle for 3 cycles to determine optimal dose. In Part 2, optimal dose determined in Part 1 will be administered on Day 1 of each 21 day cycle for 3 cycles.
DRUGBortezomib
Bortezomib 1.3 mg/m2 will be administered intravenously on Days 1,4,8, and 11 of each 21 day cycle for 3 cycles in both parts (Part 1 and Part 2).
DRUGDexamethasone
Participants will receive dexamethasone 40 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21 day cycle for 3 cycles in both parts (Part 1 and Part 2).
Sponsors
Janssen-Cilag G.m.b.H
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Cytologically or histologically diagnosed with multiple myeloma stage II/III * Participants without preceding cytostatic (tending to retard cellular activity and multiplication) treatment (pretreatment with radiation or dexamethasone is allowed) * Agree to use one of the contraception methods as defined in the protocol * Karnofsky performance status 60 percent or more * Adequate laboratory test values
Exclusion criteria
* Non-secretory multiple myeloma * Estimated life expectancy less than 3 months * History of cancer (except basal cell carcinoma) in the last 5 years * Peripheral neuropathy (disorder of the peripheral nerves) grade 2 or more * Positive human immunodeficiency virus test and active hepatitis B and/or hepatitis C * Pregnant or breast-feeding female participants
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Complete Response (CR) + Partial Response (PR) (Efficacy Set) | Up to Day 63 | CR and PR are defined by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participants With Complete Response (CR) + Partial Response (PR) (Per-protocol Analysis Set) | Up to Day 63 | CR and PR are defined by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein. |
| Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) | Up to Day 63 | Response rate was defined as the percentage of participants with response of combined CR+PR according to the EBMT criteria. As per the EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein and no increase in size or number of lytic bone lesions; PR is defined as not all CR criteria and 50 percentage or more reduction in serum monoclonal paraprotein. Percentage of participants with complete or partial response that carried the indicated cytogenetic marker is reported. Same participant could count in more than one category due to multiple responses possible |
| Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) | Up to Day 63 | Response rate was defined as the percentage of participants with response of combined CR+PR according to the EBMT criteria. As per the EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein and no increase in size or number of lytic bone lesions; PR is defined as not all CR criteria and 50 percentage or more reduction in serum monoclonal paraprotein. Percentage of participants with complete or partial response that carried the indicated cytogenetic marker is reported. Same participant could count in more than one category due to multiple responses possible. |
Countries
Germany
Participant flow
Recruitment details
401 participants were enrolled at 41 study sites in Germany.
Pre-assignment details
Out of 401 participants, 399 participants were treated in both the Parts. Out of 399 participants, 395 participants were evaluated as 4 participants who had received cyclophophamide dose of greater than 1350 mg/m\^2 per cycle in Part 1 were excluded.
Participants by arm
| Arm | Count |
|---|---|
| Cyclophosphamide + Bortezomib + Dexamethasone Cyclophosphamide + Bortezomib + Dexamethasone for three 21-day cycles | 395 |
| Total | 395 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 11 |
| Overall Study | Death | 2 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Other | 5 |
| Overall Study | Pregression of other disease | 1 |
| Overall Study | Protocol Violation | 6 |
| Overall Study | Toxicity | 13 |
Baseline characteristics
| Characteristic | Cyclophosphamide + Bortezomib + Dexamethasone |
|---|---|
| Age, Continuous | 52.4 Years STANDARD_DEVIATION 6.5 |
| Age, Customized >65 years | 16 Participants |
| Age, Customized Between 20 and 39 years | 17 Participants |
| Age, Customized Between 40 and 49 years | 109 Participants |
| Age, Customized Between 50 and 60 years | 253 Participants |
| Sex: Female, Male Female | 166 Participants |
| Sex: Female, Male Male | 229 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 392 / 395 |
| serious Total, serious adverse events | 103 / 395 |
Outcome results
Primary
Participants With Complete Response (CR) + Partial Response (PR) (Efficacy Set)
CR and PR are defined by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.
Time frame: Up to Day 63
Population: Efficacy analysis set: Participants of the safety analysis set (who received bortezomib at least once independently of accordance to the protocol) who had an evaluable investigator based assessment of success of therapy at the end of study visit (ie, assessment by local investigator as CR, PR, minimal response, stable disease, progressive disease).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclophosphamide + Bortezomib + Dexamethasone | Participants With Complete Response (CR) + Partial Response (PR) (Efficacy Set) | 334 Participants |
p-value: <0.000195% CI: [81.5, 88.8]Two - sided binomial test
Secondary
Participants With Complete Response (CR) + Partial Response (PR) (Per-protocol Analysis Set)
CR and PR are defined by the local investigator according to the current European Group for Blood and Marrow Transplantation (EBMT) criteria. According to EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein + no increase in size or number of lytic bone lesions; and PR is defined as not all CR criteria + 50 percentage or more reduction in serum monoclonal paraprotein.
Time frame: Up to Day 63
Population: Per-protocol analysis set: It includes the participants who completed the entire clinical study without major protocol violations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cyclophosphamide + Bortezomib + Dexamethasone | Participants With Complete Response (CR) + Partial Response (PR) (Per-protocol Analysis Set) | 284 Participants |
p-value: <0.000195% CI: [83.6, 91]Two-sided binomial test
Secondary
Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set)
Response rate was defined as the percentage of participants with response of combined CR+PR according to the EBMT criteria. As per the EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein and no increase in size or number of lytic bone lesions; PR is defined as not all CR criteria and 50 percentage or more reduction in serum monoclonal paraprotein. Percentage of participants with complete or partial response that carried the indicated cytogenetic marker is reported. Same participant could count in more than one category due to multiple responses possible
Time frame: Up to Day 63
Population: Efficacy analysis set. N (number of participants analyzed) signifies participants with complete or partial response. n signifies number of participants who were evaluable for each specified category (participants that carried the indicated cytogenetic marker).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) | 13q- (n=112) | 90.2 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) | t (4;14) (n=38) | 89.5 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) | 17p- (n=31) | 74.2 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) | Other (n=104) | 87.5 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Efficacy Set) | No changes (n=102) | 84.3 Percentage of participants |
Secondary
Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set)
Response rate was defined as the percentage of participants with response of combined CR+PR according to the EBMT criteria. As per the EBMT criteria, CR is defined as the absence of serum and urine monoclonal paraprotein and no increase in size or number of lytic bone lesions; PR is defined as not all CR criteria and 50 percentage or more reduction in serum monoclonal paraprotein. Percentage of participants with complete or partial response that carried the indicated cytogenetic marker is reported. Same participant could count in more than one category due to multiple responses possible.
Time frame: Up to Day 63
Population: Per-protocol analysis set. N (number of participants analyzed) signifies participants with complete or partial response. n signifies number of participants who were evaluable for each specified category (participants that carried the indicated cytogenetic marker).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) | 13q- (n=92) | 92.4 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) | t (4;14) (n=34) | 91.2 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) | 17p- (n=24) | 87.5 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) | Other (n=87) | 88.5 Percentage of participants |
| Cyclophosphamide + Bortezomib + Dexamethasone | Percentage of Participants With Complete Response + Partial Response in Relation to Cytogenetic Subgroups (Per-protocol Set) | No changes (n=87) | 85.1 Percentage of participants |