Back to resultsCarfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Carfilzomib
Lenalidomide
Dexamethasone
Lenalidomide
Lenalidomide
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring Novel Drug Combinations, Protease Inhibitors, Decreased Peripheral Neuropathy, Auto Stem Cell Transplant, Multiple Myeloma
Eligibility Criteria
- INCLUSION CRITERIA:
Newly diagnosed patients with histologically confirmed multiple myeloma (MM) based on the following criteria:
- Clonal plasma cells in the bone marrow
Measurable disease within the past 4 weeks defined by any one of the following:
- Serum monoclonal protein greater than or equal to 1.0 g/dL
- Urine monoclonal protein greater than 200 mg/24 hour
- Serum immunoglobulin free light chain greater than 10 mg/dL AND abnormal kappa/lambda ratio
Evidence of underlying end organ damage attributed to underlying plasma cell proliferative disorder meeting at least one of the following:
- Hypercalcemia: serum calcium greater than or equal to 2.65 mmol/L
- Renal Insufficiency: serum creatinine greater than 2.0 mg/dL
- Anemia: hemoglobin value less than10 g/dL or 2 g/dL less than normal reference
- Bone disease: lytic lesions, severe osteopenia or pathological fractures
- Creatinine Clearance (CrCl) greater than or equal to 60 ml/min. CrCl will be calculated by Cockcroft-Gault method. CrCl (calculated) = (140 Age) x Mass (in kilograms) x [0.85 if Female] 72 times Serum Creatinine (in mg/dL). If calculated CrCl based on Cockcroft-Gault method is <60 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must be also greater than or equal to 60 ml/min.
- Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of carfilzomib in combination with lenalidomide in patients less than18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count (ANC) greater than or equal to 1.0 K/uL, hemoglobin greater than or equal to 8 g/dL (transfusions are permissible), and platelet count greater than or equal to 75 K/uL
- Adequate hepatic function, with bilirubin less than 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3.0 times ULN.
- All study participants must be able to tolerate one of the following thromboprophylactic strategies: aspirin, low molecular weight heparin or warfarin (coumadin).
- All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist .
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 10-14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. Females of child bearing potential (FCBP) must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
- Subjects must be able to give informed consent
EXCLUSION CRITERIA:
Prior or concurrent systemic treatment for MM.
- Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with corticosteroids is permitted.
- Bisphosphonates are permitted.
- Treatment with corticosteroids for indications other than MM is permitted.
- Radiotherapy is permitted.
- Treatment for smoldering myeloma is permitted.
- Plasma cell leukemia
- Pregnant or lactating females. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide, breastfeeding should be discontinued if the mother is treated with carfilzomib and lenalidomide. These potential risks may also apply to other agents used in this study.
- Uncontrolled hypertension or diabetes
- Active hepatitis B or C infection
- Has significant cardiovascular disease with New York Heart Association (NYHA) Class III or IV symptoms, or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination. Echocardiogram will be performed if clinically warranted.
- Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting, inflammatory bowel disease, or bowel resection that would prevent absorption
- Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements
- Significant neuropathy greater than or equal to Grade 3 at baseline
- Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
- Major surgery within 1 month prior to enrollment
Recruitment Strategies:
- Patients that progress from the smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) Natural History Study (NCI Protocol: 10-C-0096) will be potential candidates.
- Other participant sources will be from outside physician referrals.
- Our ongoing natural history study and outside physician referral network has a high representation of minorities.
Sites / Locations
- National Institutes of Health Clinical Center, 9000 Rockville Pike
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Carfilzomib, Lenalidomide, Dexamethasone
Arm Description
Patients will receive 8 cycles of induction combination therapy of carfilzomib, lenalidomide, and dexamethasone (CRd). Patients achieving stable disease or better after 8 cycles of CRd will receive lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will have the option to continue extended dosing (phase II) for one additional year
Outcomes
Primary Outcome Measures
Number of Participants With Serious and Non-serious Adverse Events
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Secondary Outcome Measures
Overall Response Rate
Response is assessed by the International Myeloma Working Group Criteria. Patients who attained a partial response or better (BoR) response by the end of induction. Partial response is ≥50% reduction of serum M-protein and reduction in 24h urinary M-protein.
Progression Free Survival (PFS) at 48 Months
PFS is defined as time of start of treatment to time of progression or death, whichever occurs first. Response is assessed by the International Myeloma Working Group Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from lowest response value in the following on 2 consecutive measurements: serum M-component and/or (the absolute increase must be ≥0.5g/dl). Urine M-component and/or (the absolute increase must be ≥200mg/24h. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder.
Percentage of Responders With Duration of Response (DOR) at 48 Months
Response is assessed by the International Myeloma Working Group Criteria. DOR is measured from the time measurement criteria are met for a partial response or better until first date that recurrent or progressive disease is objectively documented. Partial response is ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24h. Progressive disease requires any one or more of the following: increase of ≥25% from lowest response value in the following on 2 consecutive measurements: serum M-component and/or (the absolute increase must be ≥0.5g/dl). Urine M-component and/or (the absolute increase must be ≥200mg/24h. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%.
Overall Survival (OS) Rate
OS is defined as the time of start of treatment to death from any cause.
Cluster of Differentiation 138 (CD138) + Plasma Cells Gene Expression Profiling on Pre and Post Carfilzomib Exposure Bone Marrow Samples
Cluster of differentiation 138+ (CD138)+ plasma cells purified from bone marrow aspirates to identify potential markers of early progression. Changes in selected genes were confirmed by quantitative polymerase chain reaction (PCR) if suggested to be related to risk of progression to multiple myeloma.
Rate of Minimal Residual Disease (MRD) by Flow Cytometry
Response is assessed by the International Myeloma Working Group Criteria. Complete response is negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. MRD is defined by M-spike, plasma cell burden, and abnormal free light chains. Immunophenotyping is performed by multi-parametric flow cytometry.
Complete Response (CR) and Minimal Residual Disease Neg (MRDneg) CR Rates at Treatment Intervals With Carfilzomib, Lenalidomide & Dexamethasone (CRd) in New Multiple Myeloma Patients After 8 Cycles of Induction, 1 Year Maintenance, and 2 Years Maintenance
Response is assessed by the International Myeloma Working Group Criteria. MRD is defined by M-spike, plasma cell burden, and abnormal free light chains (FLC). Complete response is negative immunofixation on serum, and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. Stringent complete response (sCR) is normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. Near complete response (nCR) is the absence of myeloma protein on electrophoresis, independent of immunofixation status. Very good partial response (VGPR) is serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24h. Overall response rate (ORR) is patients who attained a partial response (PR) (≥50% reduction of serum M-protein and reduction in 24h urinary M-protein) or better (BoR) response.
Full Information
NCT ID
NCT01402284
First Posted
July 23, 2011
Last Updated
February 10, 2021
Sponsor
National Cancer Institute (NCI)
Collaborators
Celgene, Onyx Therapeutics, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01402284
Brief Title
Carfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients
Official Title
Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Clinical and Correlative Phase II Study
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
July 21, 2011 (Actual)
Primary Completion Date
July 10, 2016 (Actual)
Study Completion Date
September 24, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Institute (NCI)
Collaborators
Celgene, Onyx Therapeutics, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Background:
- Carfilzomib is an experimental anti-cancer drug that has not yet been approved for treating multiple myeloma. Lenalidomide is a drug that may stop tumor growth and help the immune system kill cancer cells. Dexamethasone is a drug that helps stop inflammation. It is sometimes used to treat (alone or with other drugs) certain types of cancer, especially multiple myeloma. This combination of drugs has not been tested in people with multiple myeloma. Researchers want to see whether it is safe and effective for this group.
Objectives:
- To test the effectiveness of combined carfilzomib, lenalidomide, and dexamethasone in treating multiple myeloma.
Eligibility:
- People at least 18 years of age who have multiple myeloma that has not been treated.
Design:
Participants will be screened with a medical history and physical exam. They will also have blood and urine tests, a bone marrow sample, and molecular imaging studies.
Participants will have eight 28-day cycles of treatment. The combined study drugs will be given as tablets and injections. Those in the study will be monitored with frequent blood tests, bone marrow samples, and molecular imaging studies. In addition to current standard measures to determine clinical responses, molecular tests will be conducted to define evidence of minimal residual disease.
After the first four cycles of therapy, those who are eligible for a stem cell transplant will have stem cells collected and stored for use if the cancer returns.
After stem cell collection, participants will have the second four treatment cycles.
-, If the disease has improved or is stable at the end of eight cycles, those in the study may have another 12 cycles of low-dose (maintenance) lenalidomide alone.
Participants will have regular follow-up visits after the end of the study chemotherapy.
Detailed Description
Background:
Multiple myeloma (MM) is an incurable plasma cell neoplasm with a median survival of 3-4 years.
Novel agent combinations with proteasome inhibitors demonstrate improved response rates while increasing survival in MM patients.
A common debilitating side effect of the proteasome inhibitor bortezomib is neuropathy.
Carfilzomib is a new proteasome inhibitor with potent anti-MM effects and decreased peripheral neuropathy
Objectives:
-Evaluate toxicity, including peripheral neuropathy, of carfilzomib, lenalidomide, and dexamethasone (CRd) in untreated MM patients
Eligibility:
Newly diagnosed patients with histologically confirmed multiple myeloma
Age greater than or equal to 18 years
Creatinine Clearance (CrCl) greater than or equal to 60 ml/min. CrCl will be calculated using the Cockcroft- Gault method. If the calculated CrCl based on Cockcroft-Gault method is <60 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must also be greater than or equal to 60 ml/min.
Without serious co-morbidity that would interfere with receipt of CRd
Absolute neutrophil count (ANC) greater than or equal to 1.0 K/uL, hemoglobin greater than or equal to 8 g/dL, and platelet count greater than or equal to 75 K/uL
Adequate hepatic function, with bilirubin less than 1.5 x the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3.0 x ULN
Design:
Single arm, single stage phase II trial of combination therapy (carfilzomib, lenalidomide, and dexamethasone) for untreated multiple myeloma patients with an early stopping rule for toxicity
Patients will receive 8 cycles of induction combination therapy of CRd
Each cycle consists of 28-days
After 4 cycles of therapy, transplant eligible patients will undergo stem cell collection
Patients achieving stable disease or better after 8 cycles of CRd will receive lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will have the option to continue extended dosing (phase II) for one additional year.
Patients will have routine blood work with serum protein electrophoresis (SPEP) and free light chains monthly
Pre- and post-treatment bone marrow biopsies will be obtained for confirmation of diagnosis and correlative studies
Patients will also undergo evaluation for minimal residual disease at regular interval time points, using multi-parametric flow cytometry and fludeoxyglucose 18F-positron emission tomography - computed tomography (FDG PET-CT)
A single stage phase II design will be employed, with an early stopping rule. Unless 4 or more patients in the first 20 have Grade 3 or higher neurologic toxicity in the first 2 completed cycles, a total of 45 evaluable patients will be enrolled in this study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
Novel Drug Combinations, Protease Inhibitors, Decreased Peripheral Neuropathy, Auto Stem Cell Transplant, Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carfilzomib, Lenalidomide, Dexamethasone
Arm Type
Experimental
Arm Description
Patients will receive 8 cycles of induction combination therapy of carfilzomib, lenalidomide, and dexamethasone (CRd). Patients achieving stable disease or better after 8 cycles of CRd will receive lenalidomide extended dosing (phase I) for 12 cycles. After 12 cycles, patients will have the option to continue extended dosing (phase II) for one additional year
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis
Intervention Description
Cycle 1: 20 mg/m(2) intravenous (IV) infusion over 30 minutes on days 1 and 2, then 36 mg/m(2) IV on days 8, 9, 15, and 16 Cycle 2-8: 36mg/ m(2) IV infusion over 30 minutes on days 1, 2, 8, 9, 15, and 16
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
Cycle 1: 25 mg oral days 2-21 of 28-day cycle; Cycle 2 - 8: 25 mg oral days 1-21 of 28-day cycle; After 8 cycles of combination carfilzomib, lenalidomide, and dexamethasone (CRd), patients may continue Lenalidomide for 12 cycles; After 12 cycles of extended dosing of Lenalidomide, patients may continue Lenalidomide for one year
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
Ozurdex
Intervention Description
Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22, and 23 Cycle 2-4: 20 mg oral or IV on days 1, 2, 8, 9, 15, 16, 22, and 23 Cycle 5-8: 10 mg oral or IV on days 1, 2, 8, 9, 15, 16, 22, and 23
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
After 8 cycles of combination carfilzomib, lenalidomide, and dexamethasone (CRd), patients may continue Lenalidomide for 12 cycles
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
After 12 cycles of extended dosing of Lenalidomide, patients may continue Lenalidomide for one year
Primary Outcome Measure Information:
Title
Number of Participants With Serious and Non-serious Adverse Events
Description
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time Frame
4 years and 9 months and 2 days
Secondary Outcome Measure Information:
Title
Overall Response Rate
Description
Response is assessed by the International Myeloma Working Group Criteria. Patients who attained a partial response or better (BoR) response by the end of induction. Partial response is ≥50% reduction of serum M-protein and reduction in 24h urinary M-protein.
Time Frame
48.3 months
Title
Progression Free Survival (PFS) at 48 Months
Description
PFS is defined as time of start of treatment to time of progression or death, whichever occurs first. Response is assessed by the International Myeloma Working Group Criteria. Progressive disease requires any one or more of the following: increase of ≥25% from lowest response value in the following on 2 consecutive measurements: serum M-component and/or (the absolute increase must be ≥0.5g/dl). Urine M-component and/or (the absolute increase must be ≥200mg/24h. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%. Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in size of existing bone lesions or soft tissue plasmacytomas. Development of hypercalcemia that can be attributed solely to the plasma cell proliferative disorder.
Time Frame
48 months
Title
Percentage of Responders With Duration of Response (DOR) at 48 Months
Description
Response is assessed by the International Myeloma Working Group Criteria. DOR is measured from the time measurement criteria are met for a partial response or better until first date that recurrent or progressive disease is objectively documented. Partial response is ≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200mg per 24h. Progressive disease requires any one or more of the following: increase of ≥25% from lowest response value in the following on 2 consecutive measurements: serum M-component and/or (the absolute increase must be ≥0.5g/dl). Urine M-component and/or (the absolute increase must be ≥200mg/24h. Only in patients without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain (FLC) levels. The absolute increase must be >10mg/dl. Bone marrow plasma cell percentage: the absolute % must be ≥10%.
Time Frame
48 months
Title
Overall Survival (OS) Rate
Description
OS is defined as the time of start of treatment to death from any cause.
Time Frame
up to 6 months
Title
Cluster of Differentiation 138 (CD138) + Plasma Cells Gene Expression Profiling on Pre and Post Carfilzomib Exposure Bone Marrow Samples
Description
Cluster of differentiation 138+ (CD138)+ plasma cells purified from bone marrow aspirates to identify potential markers of early progression. Changes in selected genes were confirmed by quantitative polymerase chain reaction (PCR) if suggested to be related to risk of progression to multiple myeloma.
Time Frame
Cycle 1 Day 1, an average of 28 days ± 2 days
Title
Rate of Minimal Residual Disease (MRD) by Flow Cytometry
Description
Response is assessed by the International Myeloma Working Group Criteria. Complete response is negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. MRD is defined by M-spike, plasma cell burden, and abnormal free light chains. Immunophenotyping is performed by multi-parametric flow cytometry.
Time Frame
Day 100
Title
Complete Response (CR) and Minimal Residual Disease Neg (MRDneg) CR Rates at Treatment Intervals With Carfilzomib, Lenalidomide & Dexamethasone (CRd) in New Multiple Myeloma Patients After 8 Cycles of Induction, 1 Year Maintenance, and 2 Years Maintenance
Description
Response is assessed by the International Myeloma Working Group Criteria. MRD is defined by M-spike, plasma cell burden, and abnormal free light chains (FLC). Complete response is negative immunofixation on serum, and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in bone marrow. Stringent complete response (sCR) is normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence. Near complete response (nCR) is the absence of myeloma protein on electrophoresis, independent of immunofixation status. Very good partial response (VGPR) is serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24h. Overall response rate (ORR) is patients who attained a partial response (PR) (≥50% reduction of serum M-protein and reduction in 24h urinary M-protein) or better (BoR) response.
Time Frame
up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
INCLUSION CRITERIA:
Newly diagnosed patients with histologically confirmed multiple myeloma (MM) based on the following criteria:
Clonal plasma cells in the bone marrow
Measurable disease within the past 4 weeks defined by any one of the following:
Serum monoclonal protein greater than or equal to 1.0 g/dL
Urine monoclonal protein greater than 200 mg/24 hour
Serum immunoglobulin free light chain greater than 10 mg/dL AND abnormal kappa/lambda ratio
Evidence of underlying end organ damage attributed to underlying plasma cell proliferative disorder meeting at least one of the following:
Hypercalcemia: serum calcium greater than or equal to 2.65 mmol/L
Renal Insufficiency: serum creatinine greater than 2.0 mg/dL
Anemia: hemoglobin value less than10 g/dL or 2 g/dL less than normal reference
Bone disease: lytic lesions, severe osteopenia or pathological fractures
Creatinine Clearance (CrCl) greater than or equal to 60 ml/min. CrCl will be calculated by Cockcroft-Gault method. CrCl (calculated) = (140 Age) x Mass (in kilograms) x [0.85 if Female] 72 times Serum Creatinine (in mg/dL). If calculated CrCl based on Cockcroft-Gault method is <60 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured CrCl must be also greater than or equal to 60 ml/min.
Age greater than or equal to 18 years. Because no dosing or adverse event data are currently available on the use of carfilzomib in combination with lenalidomide in patients less than18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Absolute neutrophil count (ANC) greater than or equal to 1.0 K/uL, hemoglobin greater than or equal to 8 g/dL (transfusions are permissible), and platelet count greater than or equal to 75 K/uL
Adequate hepatic function, with bilirubin less than 1.5 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 3.0 times ULN.
All study participants must be able to tolerate one of the following thromboprophylactic strategies: aspirin, low molecular weight heparin or warfarin (coumadin).
All study participants must be registered into the mandatory RevAssist program, and be willing and able to comply with the requirements of RevAssist .
Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test within 10-14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. Females of child bearing potential (FCBP) must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
Subjects must be able to give informed consent
EXCLUSION CRITERIA:
Prior or concurrent systemic treatment for MM.
Treatment of hypercalcemia or spinal cord compression or aggressively progressing myeloma with corticosteroids is permitted.
Bisphosphonates are permitted.
Treatment with corticosteroids for indications other than MM is permitted.
Radiotherapy is permitted.
Treatment for smoldering myeloma is permitted.
Plasma cell leukemia
Pregnant or lactating females. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with carfilzomib in combination with lenalidomide, breastfeeding should be discontinued if the mother is treated with carfilzomib and lenalidomide. These potential risks may also apply to other agents used in this study.
Uncontrolled hypertension or diabetes
Active hepatitis B or C infection
Has significant cardiovascular disease with New York Heart Association (NYHA) Class III or IV symptoms, or hypertrophic cardiomyopathy, or restrictive cardiomyopathy, or myocardial infarction within 3 months prior to enrollment, or unstable angina, or unstable arrhythmia as determined by history and physical examination. Echocardiogram will be performed if clinically warranted.
Has refractory gastrointestinal (GI) disease with refractory nausea/vomiting, inflammatory bowel disease, or bowel resection that would prevent absorption
Uncontrolled intercurrent illness including but not limited to active infection or psychiatric illness/social situations that would compromise compliance with study requirements
Significant neuropathy greater than or equal to Grade 3 at baseline
Contraindication to any concomitant medication, including antivirals, anticoagulation prophylaxis, tumor lysis prophylaxis, or hydration given prior to therapy
Major surgery within 1 month prior to enrollment
Recruitment Strategies:
Patients that progress from the smoldering multiple myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) Natural History Study (NCI Protocol: 10-C-0096) will be potential candidates.
Other participant sources will be from outside physician referrals.
Our ongoing natural history study and outside physician referral network has a high representation of minorities.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dickran Kazandjian, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
12780789
Citation
International Myeloma Working Group. Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group. Br J Haematol. 2003 Jun;121(5):749-57.
Results Reference
background
PubMed Identifier
17420512
Citation
Kristinsson SY, Landgren O, Dickman PW, Derolf AR, Bjorkholm M. Patterns of survival in multiple myeloma: a population-based study of patients diagnosed in Sweden from 1973 to 2003. J Clin Oncol. 2007 May 20;25(15):1993-9. doi: 10.1200/JCO.2006.09.0100. Epub 2007 Apr 9.
Results Reference
background
PubMed Identifier
17975015
Citation
Kumar SK, Rajkumar SV, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Zeldenrust SR, Dingli D, Russell SJ, Lust JA, Greipp PR, Kyle RA, Gertz MA. Improved survival in multiple myeloma and the impact of novel therapies. Blood. 2008 Mar 1;111(5):2516-20. doi: 10.1182/blood-2007-10-116129. Epub 2007 Nov 1.
Results Reference
background
PubMed Identifier
31619706
Citation
Huang PA, Beedie SL, Chau CH, Venzon DJ, Gere S, Kazandjian D, Korde N, Mailankody S, Landgren O, Figg WD. Cereblon gene variants and clinical outcome in multiple myeloma patients treated with lenalidomide. Sci Rep. 2019 Oct 16;9(1):14884. doi: 10.1038/s41598-019-51446-9.
Results Reference
derived
PubMed Identifier
26327694
Citation
Acosta-Alvear D, Cho MY, Wild T, Buchholz TJ, Lerner AG, Simakova O, Hahn J, Korde N, Landgren O, Maric I, Choudhary C, Walter P, Weissman JS, Kampmann M. Paradoxical resistance of multiple myeloma to proteasome inhibitors by decreased levels of 19S proteasomal subunits. Elife. 2015 Sep 1;4:e08153. doi: 10.7554/eLife.08153.
Results Reference
derived
PubMed Identifier
26181891
Citation
Korde N, Roschewski M, Zingone A, Kwok M, Manasanch EE, Bhutani M, Tageja N, Kazandjian D, Mailankody S, Wu P, Morrison C, Costello R, Zhang Y, Burton D, Mulquin M, Zuchlinski D, Lamping L, Carpenter A, Wall Y, Carter G, Cunningham SC, Gounden V, Sissung TM, Peer C, Maric I, Calvo KR, Braylan R, Yuan C, Stetler-Stevenson M, Arthur DC, Kong KA, Weng L, Faham M, Lindenberg L, Kurdziel K, Choyke P, Steinberg SM, Figg W, Landgren O. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol. 2015 Sep;1(6):746-54. doi: 10.1001/jamaoncol.2015.2010.
Results Reference
derived
Links:
URL
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2011-C-0221.html
Description
NIH Clinical Center Detailed Web Page
Learn more about this trial
Carfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients
We'll reach out to this number within 24 hrs