Multiple Myeloma, Solid Tumors
Conditions
Keywords
Multiple myeloma, proteasome, Hematological, carfilzomib, PR-171
Brief summary
This is a multi-center, open-label, Phase 2 study of carfilzomib to monitor the safety and efficacy of long-term or continuing carfilzomib therapy for patients who previously completed a primary carfilzomib treatment study.
Interventions
DRUGCarfilzomib
Carfilzomib dose levels ranged from 11 to 27 mg/m² for 2- to 10-minute infusions and 36 to 56 mg/m² for 30-minute infusions. Carfilzomib doses were administered on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Dose level reduction to a minimum dose of 11 mg/m² for toxicity was permitted.
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
1. Previous completion of a carfilzomib study within 90 days prior to first dose of maintenance study drug. 2. Disease Assessments performed within 30 days prior to first dose of maintenance study drug. 3. Written informed consent in accordance with federal, local, and institutional guidelines 4. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test, with a sensitivity of at least 50 mIU/mL, within 3 days prior to first dose of maintenance study drug. 5. Subjects must agree to adhere to the study visit schedule and other study requirements and receive outpatient treatment and laboratory monitoring at the institution that administers the drug.
Exclusion criteria
1. Administration of an intervening chemotherapy between the time of previous carfilzomib study termination and first dose of maintenance study drug. 2. Pregnant or lactating females 3. Diagnosis of a new malignancy of a different tumor type.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Peripheral Neuropathy | From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma. | Participants with peripheral neuropathy or peripheral neuropathy-related adverse events, including hypoaesthesia, paraesthesia, dysaesthesia, and neuropathic pain. |
| Number of Participants With Adverse Events | From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma. | Adverse events (AEs) were assigned a severity grade using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale version 3.0. Per protocol, adverse events were collected if they led to dose modification or dose discontinuation, were grade ≥ 3 or serious, or were events of peripheral neuropathy (any grade). A serious AE is one that met one or more of the following criteria: * Death * Life threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect in the offspring of an exposed subject * Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma. | Since participants were only followed up to 30 days after administration of last dose of study drug per protocol, Kaplan-Meier estimates of overall survival were not calculated. The number of participants who died within 30 days after administration of last dose of study drug is reported. |
| Progression-free Survival | From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma. | Progression-free survival (PFS) was defined as the time between the start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurred first. Disease progression was determined by the local investigator for regimens with the same baseline using the International Uniform Response Criteria (IMWG-URC) for participants with multiple myeloma and Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid tumor participants. PFS was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency. |
| Time to Progression | From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma. | Time to progression (TTP) was defined as the time between start of treatment to the first documentation of disease progression. TTP was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency. |
Countries
Canada, United States
Participant flow
Recruitment details
This study was conducted at 23 centers in the United States and Canada from April 2009 to May 2017.
Participants by arm
| Arm | Count |
|---|---|
| Solid Tumors Participants with solid tumors received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib. | 9 |
| Multiple Myeloma Participants with multiple myeloma received carfilzomib administered intravenously, using the same method, frequency, and dose level as in the last cycle of the participant's previous carfilzomib study. Treatment was continued until confirmation of disease progression, diagnosis of new malignancy, unacceptable toxicity, investigator discretion, voluntary withdrawal, or commercial availability of carfilzomib. | 91 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did Not Receive Study Drug | 0 | 1 |
| Overall Study | Fatal Adverse Event | 1 | 4 |
| Overall Study | Fatal Progressive Disease | 0 | 1 |
| Overall Study | Non-fatal Adverse Event | 1 | 0 |
| Overall Study | Non-fatal Progressive Disease | 0 | 8 |
| Overall Study | Other | 0 | 4 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 6 |
Baseline characteristics
| Characteristic | Solid Tumors | Multiple Myeloma | Total |
|---|---|---|---|
| Age, Continuous | 61.2 years STANDARD_DEVIATION 12.75 | 63.2 years STANDARD_DEVIATION 9.82 | 63.0 years STANDARD_DEVIATION 10.05 |
| Age, Customized < 65 years | 5 Participants | 47 Participants | 52 Participants |
| Age, Customized ≥ 65 years | 4 Participants | 44 Participants | 48 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 (Fully active) | 6 Participants | 39 Participants | 45 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 (Restricted but ambulatory) | 3 Participants | 42 Participants | 45 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 (Ambulatory but unable to work) | 0 Participants | 10 Participants | 10 Participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 0 Participants | 4 Participants | 4 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 11 Participants | 11 Participants |
| Race/Ethnicity, Customized Hispanic | 0 Participants | 5 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 71 Participants | 80 Participants |
| Sex: Female, Male Female | 6 Participants | 38 Participants | 44 Participants |
| Sex: Female, Male Male | 3 Participants | 53 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 9 | 7 / 91 |
| other Total, other adverse events | 6 / 9 | 69 / 91 |
| serious Total, serious adverse events | 5 / 9 | 57 / 91 |
Outcome results
Primary
Number of Participants With Adverse Events
Adverse events (AEs) were assigned a severity grade using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading scale version 3.0. Per protocol, adverse events were collected if they led to dose modification or dose discontinuation, were grade ≥ 3 or serious, or were events of peripheral neuropathy (any grade). A serious AE is one that met one or more of the following criteria: * Death * Life threatening * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly/birth defect in the offspring of an exposed subject * Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes above.
Time frame: From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.
Population: All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Solid Tumors | Number of Participants With Adverse Events | Serious adverse events | 5 participants |
| Solid Tumors | Number of Participants With Adverse Events | Adverse event ≥ grade 3 | 5 participants |
| Solid Tumors | Number of Participants With Adverse Events | Fatal adverse events | 1 participants |
| Solid Tumors | Number of Participants With Adverse Events | AE leading to discontinuation of carfilzomib | 5 participants |
| Solid Tumors | Number of Participants With Adverse Events | Any adverse event | 7 participants |
| Multiple Myeloma | Number of Participants With Adverse Events | AE leading to discontinuation of carfilzomib | 20 participants |
| Multiple Myeloma | Number of Participants With Adverse Events | Any adverse event | 84 participants |
| Multiple Myeloma | Number of Participants With Adverse Events | Adverse event ≥ grade 3 | 66 participants |
| Multiple Myeloma | Number of Participants With Adverse Events | Serious adverse events | 57 participants |
| Multiple Myeloma | Number of Participants With Adverse Events | Fatal adverse events | 7 participants |
Primary
Number of Participants With Peripheral Neuropathy
Participants with peripheral neuropathy or peripheral neuropathy-related adverse events, including hypoaesthesia, paraesthesia, dysaesthesia, and neuropathic pain.
Time frame: From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.
Population: All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Solid Tumors | Number of Participants With Peripheral Neuropathy | 1 participants |
| Multiple Myeloma | Number of Participants With Peripheral Neuropathy | 15 participants |
Secondary
Overall Survival
Since participants were only followed up to 30 days after administration of last dose of study drug per protocol, Kaplan-Meier estimates of overall survival were not calculated. The number of participants who died within 30 days after administration of last dose of study drug is reported.
Time frame: From first dose of study drug to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.
Population: All participants who received at least 1 dose of carfilzomib after enrollment in PX-171-010.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Solid Tumors | Overall Survival | 1 participants |
| Multiple Myeloma | Overall Survival | 7 participants |
Secondary
Progression-free Survival
Progression-free survival (PFS) was defined as the time between the start of treatment and first evidence of documented disease progression or death (due to any cause), whichever occurred first. Disease progression was determined by the local investigator for regimens with the same baseline using the International Uniform Response Criteria (IMWG-URC) for participants with multiple myeloma and Response Evaluation Criteria in Solid Tumors (RECIST) criteria for solid tumor participants. PFS was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.
Time frame: From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.
Population: Enrolled participants excluding those with no postbaseline endpoint data subsequent to at least 1 dose of the study drug on the PX-171-010 protocol and participants who lacked baseline data for those analyses that required baseline data. Only participants with regimens that continued from the initial study without baseline being reset are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Solid Tumors | Progression-free Survival | 41.9 months |
| Multiple Myeloma | Progression-free Survival | 19.6 months |
Secondary
Time to Progression
Time to progression (TTP) was defined as the time between start of treatment to the first documentation of disease progression. TTP was re-calculated whenever the baseline was reset due to addition of new anti-cancer therapy or increase of carfilzomib dose/frequency.
Time frame: From first dose of study drug in study PX-171-010 to 30 days after the last dose; median duration of treatment was 14 weeks for participants with solid tumors and 44 weeks for participants with multiple myeloma.
Population: Enrolled participants excluding those with no postbaseline endpoint data subsequent to at least 1 dose of the study drug on the PX-171-010 protocol and participants who lacked baseline data for those analyses that required baseline data Only participants with regimens that continued from the initial study without baseline being reset are included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Solid Tumors | Time to Progression | NA months |
| Multiple Myeloma | Time to Progression | 19.6 months |