Multiple Myeloma
Conditions
Keywords
Multiple Myeloma, Revlimid
Brief summary
The study evaluated the safety of Lenalidomide monotherapy in participants with advanced multiple myeloma who had discontinued treatment with combination thalidomide plus high-dose dexamethasone or high-dose dexamethasone alone in studies Thal-MM-003, CC-5013-MM-009 and CC-5013-MM-010 due to the development of documented disease progression or the inability to tolerate the lowest dosing regimen per previous protocol of thalidomide and/or high-dose dexamethasone without grade 3 or 4 toxicity.
Interventions
DRUGCC-5013
Oral 25mg daily on Days 1-21 every 28 days.
DRUGLenalidomide
Oral Lenalidomide 25mg daily on Days 1-21 every 28 days.
Sponsors
Celgene
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
* Understand and voluntarily sign an informed consent form. * Age ≥ 18 years at time of signing the informed consent form. * Able to adhere to the study visit schedule and other protocol requirements * Participants with multiple myeloma and were enrolled in either THAL-MM-003, CC-5013-MM-009, or CC-5013-MM-010 and discontinued study therapy with thalidomide and high-dose dexamethasone or high-dose dexamethasone alone due to: documented disease progression OR inability to tolerate the lowest dosing regimen allowed on previous protocol without a grade 3 or 4 toxicity. * Eastern Cooperative Oncology Group (ECOG) performance status score 0,1,2 * Recovery from thalidomide or dexamethasone-related toxicity to ≤ grade 2 (NCI CTC) * Females of child-bearing potential (FCBP) must agree to using two methods of contraception
Exclusion criteria
* Prior development of a ≥ grade 2 allergic reaction/hypersensitivity or prior development of a grade ≥ 3 rash or desquamation while taking thalidomide National Cancer Institute Common toxicity Criteria (NCI CTC) * Use of any standard/experimental anti-myeloma therapy within 28 days of randomization or use of any experimental non-drug therapy within 56 days of initiation of drug treatment * Any serious medical condition, laboratory abnormality, or psychiatric illness that will prevent the participant from signing the informed consent form or that will place the participant at an unacceptable risk for toxicity if he/she participates in the study. * Pregnant or lactating females. * Prior therapy with CC-5013; prior history of malignancies, other than multiple myeloma (except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast), unless subject has been free of disease for ≥ 5 years * More than 4 months has elapsed since the last dose of study drug was administered on study Tal MM-003, CC-5013-MM-009, CC-5013-MM-010 * Absolute neutrophil count (ANC) \<1,000cells/mm\^3 (1.0 X 10\^9/L) * Platelet count \<75,000/mm\^3 (30 X 10\^9/L) for those with \<50% if the bone marrow nucleated cells re plasma cells; Platelet count \<30,000/mm\^3 (30 X 10\^9/L) for those with \<50% if the bone marrow nucleated cells re plasma cells * Serum creatinine \>2.5mg/dL; serum SGOT/AST or SGPT/ALT x upper limits of normal (ULN) * Serum total bilirubin \>2.0mg/d/L
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AE) During the Treatment Phase | Until data cut-off of 22 Oct 2009; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. Maximum exposure to Lenalidomide treatment was 1260 days. | An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; |
| Number of Participants With Adverse Events (AE) During the Extension Phase | From 22 Oct 2009 to November 2013; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. | An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal; |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Progression | Up to 70 months | Time to progression based on the myeloma response determination criteria developed by Bladé et al 1998 and is defined as the time from registration to the first documented progression. The progressive disease criteria included increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia. |
| Myeloma Response Rate | Up to 70 months | Myeloma response determination criteria developed by Bladé et al 1998. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens. |
| Duration of Response | Up to 70 months | Duration of response based on the Myeloma response determination criteria developed by Bladé et al 1998 and defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on International Myeloma Working Group (IMWG) criteria. |
Countries
Russia, Ukraine
Participant flow
Recruitment details
This was an international, open-label single arm study of oral lenalidomide in participants with multiple myeloma who had previously received high dose dexamethasone alone or in combination with thalidomide in the study NCT 00057564, or previously received high dose dexamethasone alone in studies NCT 00056160 and NCT 00424047.
Pre-assignment details
To be eligible participants must have developed disease progression or were unable to tolerate the lowest dosing regimen of thalidomide and/or high-dose dexamethasone without Grade 3 or 4 toxicity
Participants by arm
| Arm | Count |
|---|---|
| Lenalidomide 25mg (CC-5013) Oral 25mg daily on Days 1-21 every 28 days | 330 |
| Total | 330 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Extension Phase | Adverse Event | 2 |
| Extension Phase | Lack of therapeutic effect | 2 |
| Extension Phase | Lost to Follow-up | 1 |
| Extension Phase | Other | 9 |
| Extension Phase | Progressive Disease | 6 |
| Extension Phase | Withdrawal by Subject | 1 |
| Treatment Phase | Adverse Event | 46 |
| Treatment Phase | Death | 14 |
| Treatment Phase | Lack of therapeutic effect | 13 |
| Treatment Phase | Lost to Follow-up | 2 |
| Treatment Phase | Other | 40 |
| Treatment Phase | Progression of Disease | 181 |
| Treatment Phase | Withdrawal by Subject | 13 |
Baseline characteristics
| Characteristic | Lenalidomide 25mg (CC-5013) |
|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 9.43 |
| Age, Customized ≤ 65 years | 194 participants |
| Age, Customized > 65 years | 136 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 = Fully Active | 95 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 = Restricted Activity | 178 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 = Ambulatory; not able to work | 44 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 = Limited Self Care | 1 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 4 = Completely Disabled | 0 participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status Missing= Unspecified | 12 participants |
| Race/Ethnicity, Customized Asian/Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 14 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants |
| Race/Ethnicity, Customized White | 309 Participants |
| Sex: Female, Male Female | 137 Participants |
| Sex: Female, Male Male | 193 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 330 | 6 / 21 |
| serious Total, serious adverse events | 177 / 330 | 5 / 21 |
Outcome results
Primary
Number of Participants With Adverse Events (AE) During the Extension Phase
An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal;
Time frame: From 22 Oct 2009 to November 2013; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit.
Population: Included participants who were enrolled in the extension phase. The safety population included participants enrolled in the study and had received at least one dose of lenalidomide.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Extension Phase | ≥ 1 Adverse Event (AE) | 13 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Extension Phase | Adverse Event related to study drug | 1 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Extension Phase | Adverse Event NCI CTC (Version2.0) Grade 3 or 4 | 5 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Extension Phase | ≥ 1 Serious Adverse Event (SAE) | 5 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Extension Phase | ≥ 1 AE leading to discontinuation of study drug | 1 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Extension Phase | ≥ 1 AE leading to dose reduction/interruption | 3 participants |
Primary
Number of Participants With Adverse Events (AE) During the Treatment Phase
An AE is any sign, symptom, illness, or diagnosis (either observed or volunteered) that appears or worsens during the course of the study Serious adverse event (SAE) = any AE which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE is defined as any AE occurring or worsening on or after the first dose of study drug and within 30 days after the last dose of study drug. Safety and severity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 2.0; Severity of AEs were graded (including second primary malignancies) as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe; Grade 4- Life-threatening; Grade 5-Fatal;
Time frame: Until data cut-off of 22 Oct 2009; AEs/SAEs were recorded from informed consent to 30 days post treatment discontinuation visit. Maximum exposure to Lenalidomide treatment was 1260 days.
Population: The safety population included participants enrolled in the study and had received at least one dose of lenalidomide.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Treatment Phase | Adverse Event (AE) | 327 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Treatment Phase | Adverse Event related to study drug | 268 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Treatment Phase | Adverse Event NCI CTC (Version2.0) Grade 3 or 4 | 256 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Treatment Phase | Serious Adverse Event (SAE) | 177 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Treatment Phase | AE leading to discontinuation of study drug | 52 participants |
| Lenalidomide 25mg (CC-5013) | Number of Participants With Adverse Events (AE) During the Treatment Phase | AE leading to dose reduction/interruption | 210 participants |
Secondary
Duration of Response
Duration of response based on the Myeloma response determination criteria developed by Bladé et al 1998 and defined as time from the initial documented response (partial response or better) to confirmed disease progression, based on International Myeloma Working Group (IMWG) criteria.
Time frame: Up to 70 months
Population: Duration of response not analyzed per the sponsors decision.
Secondary
Myeloma Response Rate
Myeloma response determination criteria developed by Bladé et al 1998. Complete Response (CR):Disappearance of monoclonal paraprotein. Remission Response (RR):75-99% reduction in monoclonal paraprotein/90-99% reduction in 24-hr urinary light chain excretion. Partial Response (PR):50-74% reduction in monoclonal paraprotein/50-89% reduction in 24-hr urinary light chain excretion. Stable Disease (SD):Criteria for PR or PD not met. Plateau Phase:If PR, stable monoclonal paraprotein (within 25% above or below nadir)/stable soft tissue plasmacytomas. Progressive Disease (PD):Disease worsens.
Time frame: Up to 70 months
Population: Myeloma Response Rate not analyzed per the sponsors decision.
Secondary
Time to Progression
Time to progression based on the myeloma response determination criteria developed by Bladé et al 1998 and is defined as the time from registration to the first documented progression. The progressive disease criteria included increasing monoclonal paraprotein levels, bone marrow findings, worsening lytic bone disease, progressively enlarging extramedullary plasmacytomas, or hypercalcemia.
Time frame: Up to 70 months
Population: Time to progression not analyzed per the sponsors decision.