Multiple Myeloma, Plasma Cell Neoplasm
Conditions
Keywords
Refractory Multiple Myeloma, Relapsed Multiple Myeloma, Multiple Myeloma with Renal Dysfunction, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma
Brief summary
Patients with previously treated multiple myeloma and kidney dysfunction will be treated with lenalidomide and low-dose dexamethasone. Phase I will study the side effects and best dose of lenalidomide when given together with low-dose dexamethasone therapy. After the maximum safe and tolerated dose is found in Phase I, the study will proceed to Phase II. Phase II will study how well the the treatment works in patients with previously treated (relapsed or refractory) multiple myeloma and kidney dysfunction. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with dexamethasone may kill more cancer cells. Lenalidomide and dexamethasone may have different effects in patients who have changes in their kidney function.
Detailed description
Multiple Myeloma (MM) affects approximately 20,000 Americans annually and remains an incurable hematologic malignancy characterized by frequent early response followed by universal treatment relapse necessitating multiple sequential therapeutic regimens. Until recently, few effective therapies existed. Several novel agents for MM have now become available including the immunomodulatory drugs thalidomide, lenalidomide, as well as the proteasome inhibitor, bortezomib. Each of these agents is undergoing extensive clinical evaluation in combination with other therapies to produce unprecedented response rates in newly diagnosed and relapsed MM. Lenalidomide has proven to be a highly effective treatment agent, particularly when used in combination with dexamethasone but is renally excreted and little information is available about its use in myeloma patients with impaired kidney function (20% have renal failure at some time after diagnosis). Defining a safe and effective dose of lenalidomide to use is a critical step in MM treatment. OUTLINE: This is a Phase I, dose-escalation study of lenalidomide followed by a Phase II study. Patients are stratified according to degree of renal dysfunction (moderate \[creatinine clearance 30-60 mL/min\] vs severe \[creatinine clearance \<30 mL/min and does not require dialysis\] vs end-stage renal disease \[creatinine clearance \<30 mL/min and requires dialysis\]). Patients receive oral lenalidomide on days 1-21 and low-dose oral dexamethasone 40 mg on days 1, 8, 15, and 22. There is a 7 day rest (days 22-28) from lenalidomide. Each cycle is 28 days and repeated in the absence of disease progression or unacceptable toxicity. Patients enrolled in the phase II portion of the study will undergo blood sample collection periodically for pharmacokinetic analysis of lenalidomide (Mayo Clinic sites only). After completion of study treatment, patients are followed every 6 months for up to 3 years.
Interventions
DRUGLenalidomide
Given by mouth days 1-21 of a 28-day cycle. There is a 7 day rest (days 22-28). Continue until disease progression or unacceptable toxicity.
DRUGDexamethasone
40 mg given by mouth days 1, 8, 15 and 22 of a 28-day cycle. Continue until disease progression or unacceptable toxicity.
DRUGAnticoagulants
Anticoagulation consisted of aspirin at either 81 mg/day or 325 mg/day at the physician's discretion. Heparin, low molecular weight heparin, or coumadin could be used if the patient was intolerant to aspirin.
Sponsors
Celgene
PrECOG, LLC.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with previously treated multiple myeloma. * Measurable disease assessed by one of the following ≤21 days prior to registration: * Serum monoclonal protein ≥1 g by protein electrophoresis * Urine monoclonal protein \>200 mg on 24 hour electrophoresis * Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa to lambda free light chain ratio * Monoclonal bone marrow plasmacytosis ≥30% (evaluable disease) * If both serum and urine m-components are present, both must be followed in order to evaluate response. * All previous cancer therapy including chemotherapy, radiation, hormonal therapy and surgery, must be discontinued ≥2 weeks prior to registration. * Age ≥18 years. * Eastern Cooperative Oncology Group (ECOG) performance status 0-2. * Acceptable organ and marrow function ≤21 days prior to registration: * Absolute neutrophil count (ANC) ≥1000/mm³ * Platelet count ≥75,000/mm³ * Total bilirubin ≤2 mg/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 x upper limit of normal * Renal impairment at baseline as measured by serum creatinine clearance (CrCl) ≤60 mL/min ≤21 days prior to registration. * Females of Childbearing Potential (FCBP) must have a negative pregnancy test within 10-14 days and again within 24 hours of starting Cycle 1 and must use an effective double-method contraception for ≥28 days prior to, during, and for ≥28 days after completion of study therapy. * Able to take required prophylactic anticoagulation. * Able to understand and willingness to sign a written informed consent. * Willing to provide blood samples for research purposes (Mayo Clinic sites only). * If previously received lenalidomide, demonstration of clinical response of any duration or stable disease with progression-free interval of ≥6 months from start of that therapy.
Exclusion criteria
* Concurrent use of other anti-cancer agents or treatments. Growth factors and bisphosphonates are allowed as medically indicated. Steroids may be used with an equivalency of up to 20 mg of Prednisone per day as long as the dose has not been adjusted upwards in past 2 weeks prior to study registration. * Uncontrolled intercurrent illness including, but not limited to, any of the following: * Ongoing or active infection requiring IV antibiotics * Symptomatic congestive heart failure * Unstable angina pectoris * Uncontrolled cardiac arrhythmia * Psychiatric illness/social situation that would limit compliance with study requirements. * Any of the following as this regimen may be harmful to a developing fetus or nursing child: * Pregnant women * Breast-feeding women * Men or women of childbearing potential or their sexual partners who are unwilling to employ adequate contraception. * HIV-positive patients on combination antiretroviral therapy. * Known hypersensitivity to thalidomide or other immunomodulatory drugs. * History of Stevens-Johnson syndrome characterized by a desquamating rash while taking thalidomide or similar drugs. * Other active malignancy except for non melanoma skin cancer or in situ cervical or breast cancer. * Concurrent radiation therapy, except for palliation of a single painful bone lesion or fracture.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | First cycle of therapy (28 days) | Dose Limiting Toxicity (DLT) was defined as any of the following events determined by the investigator to be possibly, probably, or definitely related to lenalidomide within the first cycle of therapy irrespective of whether the adverse events resolved: * Grade 3 or higher neutropenia with fever ≥38.5 degrees C * Grade 4 neutropenia ≥7 days * Grade 4 or higher thrombocytopenia * Other non-hematologic Grade 4 or higher adverse event not present prior to starting therapy or not due to underlying cause |
| Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR] | 56 months | Per International Myeloma Working Group criteria, complete response (CR): negative immunofixation of serum and urine, normalization of free light chain (FLC) ratio if at study entry FLC was only measurable non-bone parameter, \<5% plasma cells in bone marrow, disappearance of any soft tissue plasma cytomas; stringent complete response (sCR): all of above, + normal serum FLC ratio in all patients and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; partial response (PR): \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \< 200 mg per 24 hours, \>=50% decrease in difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio, \>=50% reduction in bone marrow plasma cells, if baseline percentage was \>=30%, \>=50% reduction in size of soft tissue plasmacytoma; very good partial response (VGPR): PR + improvements in serum and urine M-components |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | 56 months | The highest degree of any adverse event experienced by each patient, as assessed by NCI CTCAE Version 4, with an attribution of possibly, probably, or definitely related to treatment. Reportable adverse events included those occurring while on treatment or within 30 days of the end of treatment. |
| Renal Function Over Time | 56 months | To describe renal function over time and to evaluate the safety profile of a onetime increase in lenalidomide dose at least 2 cycles after start of treatment due to improved renal function. |
| Overall Survival Time | 56 months | Overall survival is the time from registration to death from any cause. Patients alive at the time of analysis were censored at the date last known alive. |
| Progression-free Survival | 56 months | Progression-free survival is the time from registration to disease progression or death. Patients alive without disease progression were censored at the time of the last disease assessment. |
| Pharmacokinetics of Lenalidomide in Impaired Renal Function | 56 months | To determine the pharmacokinetics of lenalidomide administration in myeloma patients with impaired renal function (pharmacokinetic analysis will be performed in up to 12 consented Mayo Clinic subjects treated during the Phase II component of the trial (only). |
| Duration of Response | 56 months | Duration of response was defined as time between the onset of response and disease progression in months, among patients treated at the recommended phase II dose who experienced a response to treatment. Per criteria of the International Myeloma Working Group, progressive disease was defined as one of the following: increase of 25% from best confirmed response in serum M-component, urine M-component, free light chain (FLC), bone marrow plasma cell percentage, or development of new or increase in size of bone lesions or soft tissue plasma cytomas. Development of hypercalcemia that can be attributed solely to the myeloma also constituted progression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A=30-60 CrCl (mL/Min) Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
Group A=30-60 CrCl (mL/min): Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II. | 29 |
| Group B=CrCL<30 mL/Min Not on Dialysis Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
Group B=CrCL\<30 mL/min not on dialysis: Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II. | 19 |
| Group C=CrCL<30 mL/Min and on Dialysis Lenalidomide days 1-21 and Dexamethasone 40 mg days 1, 8, 15 and 22 every 28 days. Phase I will determine the dose of lenalidomide to be used in Phase II.
Group C=CrCL\<30 mL/min and on dialysis: Each Cycle=28 days. Lenalidomide by mouth days 1-21 and Dexamethasone 40 mg by mouth days 1, 8, 15 and 22. There is a 7 day rest (days 22-28) from lenalidomide. Continue until disease progression or unacceptable toxicity. Phase I will determine the dose of lenalidomide to be used in Phase II.
Dialysis includes hemodialysis or peritoneal dialysis. When lenalidomide and/or dexamethasone treatment occurs on a dialysis day, lenalidomide and/or dexamethasone must be taken after dialysis. | 14 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Dose Level 1 | Adverse Event | 1 | 0 | 0 | 2 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Level 1 | Physician Decision | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Dose Level 1 | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level 2 | Death | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level 2 | Intercurrent Illness/Other Treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Dose Level 2 | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level 2 | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level 3 | Adverse Event | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level 3 | Ineligible/Withdrew before Treatment | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Dose Level 3 | Intercurrent Illness/Alternative Therapy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Dose Level 3 | Withdrawal by Subject | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Dose Level 4 | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Dose Level 4 | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 |
| Dose Level 4 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Expansion Cohort | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Expansion Cohort | Death | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Expansion Cohort | Physician Decision | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Expansion Cohort | Study Closure | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Expansion Cohort | Withdrawal by Subject | 0 | 0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group A=30-60 CrCl (mL/Min) | Group B=CrCL<30 mL/Min Not on Dialysis | Group C=CrCL<30 mL/Min and on Dialysis | Total |
|---|---|---|---|---|
| Age, Continuous | 73 years | 72 years | 64 years | 71.5 years |
| Creatinine Clearance | 42.6 mL/min | 22.8 mL/min | 11.5 mL/min | 27.4 mL/min |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 29 Participants | 18 Participants | 14 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 26 Participants | 16 Participants | 10 Participants | 52 Participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 6 Participants | 31 Participants |
| Sex: Female, Male Male | 16 Participants | 7 Participants | 8 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 6 | 1 / 3 | 0 / 6 | 4 / 14 | 0 / 3 | 0 / 3 | 0 / 3 | 0 / 8 | 0 / 2 | 0 / 3 | 1 / 3 | 1 / 3 | 0 / 5 |
| other Total, other adverse events | 5 / 6 | 2 / 3 | 6 / 6 | 14 / 14 | 1 / 3 | 3 / 3 | 3 / 3 | 8 / 8 | 2 / 2 | 1 / 3 | 2 / 3 | 3 / 3 | 4 / 5 |
| serious Total, serious adverse events | 5 / 6 | 2 / 3 | 5 / 6 | 10 / 14 | 3 / 3 | 3 / 3 | 1 / 3 | 5 / 8 | 1 / 2 | 2 / 3 | 3 / 3 | 3 / 3 | 4 / 5 |
Outcome results
Primary
Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy
Dose Limiting Toxicity (DLT) was defined as any of the following events determined by the investigator to be possibly, probably, or definitely related to lenalidomide within the first cycle of therapy irrespective of whether the adverse events resolved: * Grade 3 or higher neutropenia with fever ≥38.5 degrees C * Grade 4 neutropenia ≥7 days * Grade 4 or higher thrombocytopenia * Other non-hematologic Grade 4 or higher adverse event not present prior to starting therapy or not due to underlying cause
Time frame: First cycle of therapy (28 days)
Population: Patients treated during the dose finding phase of the study
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A Lenalidomide 10 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group A Lenalidomide 15 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group A Lenalidomide 25 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group B Lenalidomide 15 mg/2 Days | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group B Lenalidomide 25 mg/2 Days | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group B Lenalidomide 15 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group B Lenalidomide 25 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group C Lenalidomide 15 mg 3x/Week | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group C Lenalidomide 10 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group C Lenalidomide 15 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
| Group C Lenalidomide 25 mg/Day | Number of Participants in Phase I Component With Dose Limiting Toxicities During the First Cycle of Therapy | 0 Participants |
Comparison: Recommended Phase 2 dose for Group A
Comparison: Recommended phase 2 dose for patients in Group B
Comparison: Recommended phase 2 dose for Group C
Primary
Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR]
Per International Myeloma Working Group criteria, complete response (CR): negative immunofixation of serum and urine, normalization of free light chain (FLC) ratio if at study entry FLC was only measurable non-bone parameter, \<5% plasma cells in bone marrow, disappearance of any soft tissue plasma cytomas; stringent complete response (sCR): all of above, + normal serum FLC ratio in all patients and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; partial response (PR): \>=50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by \>=90% or to \< 200 mg per 24 hours, \>=50% decrease in difference between involved and uninvolved FLC levels or a 50% decrease in level of involved FLC with 50% decrease in ratio, \>=50% reduction in bone marrow plasma cells, if baseline percentage was \>=30%, \>=50% reduction in size of soft tissue plasmacytoma; very good partial response (VGPR): PR + improvements in serum and urine M-components
Time frame: 56 months
Population: Patients treated at the recommended phase II dose
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A Lenalidomide 10 mg/Day | Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR] | 60.0 percentage of participants |
| Group A Lenalidomide 15 mg/Day | Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR] | 60.0 percentage of participants |
| Group A Lenalidomide 25 mg/Day | Percentage of Participants Who Experience a Response [sCR, CR, VGPR, PR] | 20.0 percentage of participants |
Secondary
Duration of Response
Duration of response was defined as time between the onset of response and disease progression in months, among patients treated at the recommended phase II dose who experienced a response to treatment. Per criteria of the International Myeloma Working Group, progressive disease was defined as one of the following: increase of 25% from best confirmed response in serum M-component, urine M-component, free light chain (FLC), bone marrow plasma cell percentage, or development of new or increase in size of bone lesions or soft tissue plasma cytomas. Development of hypercalcemia that can be attributed solely to the myeloma also constituted progression.
Time frame: 56 months
Population: Patients treated at the recommended phase II dose who experienced a response to treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A Lenalidomide 10 mg/Day | Duration of Response | 21.8 Months |
| Group A Lenalidomide 15 mg/Day | Duration of Response | 8.4 Months |
| Group A Lenalidomide 25 mg/Day | Duration of Response | 25.4 Months |
Secondary
Overall Survival Time
Overall survival is the time from registration to death from any cause. Patients alive at the time of analysis were censored at the date last known alive.
Time frame: 56 months
Population: Eligible, treated patients
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A Lenalidomide 10 mg/Day | Overall Survival Time | 20.8 months |
| Group A Lenalidomide 15 mg/Day | Overall Survival Time | 20.0 months |
| Group A Lenalidomide 25 mg/Day | Overall Survival Time | NA months |
Secondary
Pharmacokinetics of Lenalidomide in Impaired Renal Function
To determine the pharmacokinetics of lenalidomide administration in myeloma patients with impaired renal function (pharmacokinetic analysis will be performed in up to 12 consented Mayo Clinic subjects treated during the Phase II component of the trial (only).
Time frame: 56 months
Population: As only 1 patient was enrolled from Mayo Clinic during the Phase II component of the study, samples were neither collected nor analyzed for this endpoint.
Secondary
Progression-free Survival
Progression-free survival is the time from registration to disease progression or death. Patients alive without disease progression were censored at the time of the last disease assessment.
Time frame: 56 months
Population: Patients treated at the recommended phase II dose
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A Lenalidomide 10 mg/Day | Progression-free Survival | 12.6 Months |
| Group A Lenalidomide 15 mg/Day | Progression-free Survival | 11.4 Months |
| Group A Lenalidomide 25 mg/Day | Progression-free Survival | NA Months |
Secondary
Renal Function Over Time
To describe renal function over time and to evaluate the safety profile of a onetime increase in lenalidomide dose at least 2 cycles after start of treatment due to improved renal function.
Time frame: 56 months
Population: This outcome was not analyzed because the dose increase was not implemented.
Secondary
Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient
The highest degree of any adverse event experienced by each patient, as assessed by NCI CTCAE Version 4, with an attribution of possibly, probably, or definitely related to treatment. Reportable adverse events included those occurring while on treatment or within 30 days of the end of treatment.
Time frame: 56 months
Population: All patients who started treatment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 3 participants |
| Group A Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 1 participants |
| Group A Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 0 participants |
| Group A Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 2 participants |
| Group A Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group A Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group A Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group A Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 1 participants |
| Group A Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 1 participants |
| Group A Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group A Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 0 participants |
| Group A Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 1 participants |
| Group A Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group A Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 1 participants |
| Group A Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 4 participants |
| Group A Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group A Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 1 participants |
| Group A Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group B Lenalidomide 15 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 3 participants |
| Group B Lenalidomide 15 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group B Lenalidomide 15 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group B Lenalidomide 15 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 4 participants |
| Group B Lenalidomide 15 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 6 participants |
| Group B Lenalidomide 15 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 1 participants |
| Group B Lenalidomide 25 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 1 participants |
| Group B Lenalidomide 25 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 1 participants |
| Group B Lenalidomide 25 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 1 participants |
| Group B Lenalidomide 25 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group B Lenalidomide 25 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group B Lenalidomide 25 mg/2 Days | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 0 participants |
| Group B Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 1 participants |
| Group B Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 1 participants |
| Group B Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 0 participants |
| Group B Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group B Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 1 participants |
| Group B Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group B Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group B Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 1 participants |
| Group B Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 0 participants |
| Group B Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 1 participants |
| Group B Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 1 participants |
| Group B Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group C Lenalidomide 15 mg 3x/Week | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 3 participants |
| Group C Lenalidomide 15 mg 3x/Week | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 1 participants |
| Group C Lenalidomide 15 mg 3x/Week | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 1 participants |
| Group C Lenalidomide 15 mg 3x/Week | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group C Lenalidomide 15 mg 3x/Week | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 1 participants |
| Group C Lenalidomide 15 mg 3x/Week | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 2 participants |
| Group C Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group C Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 1 participants |
| Group C Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 0 participants |
| Group C Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 1 participants |
| Group C Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 0 participants |
| Group C Lenalidomide 10 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 3 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 0 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 1 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 1 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 1 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 1 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 2 participants |
| Group C Lenalidomide 15 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 1 | 0 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 4 | 0 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | None | 2 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 3 | 3 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 5 | 0 participants |
| Group C Lenalidomide 25 mg/Day | Worst Degree Treatment-Related Adverse Events Across All Event Types Per Patient | Grade 2 | 0 participants |