Carfilzomib, Lenalidomide, and Dexamethasone in New Multiple Myeloma Patients

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT01402284
Collaborator
Celgene (Industry), Onyx Therapeutics, Inc. (Industry)
45
1
1
110.2
0.4

Study Details

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Carfilzomib, Lenalidomide, and Dexamethasone in Newly Diagnosed Multiple Myeloma: Clinical and Correlative Phase II Study
Actual Study Start Date :
Jul 21, 2011
Actual Primary Completion Date :
Jul 10, 2016
Actual Study Completion Date :
Sep 24, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Carfilzomib, Lenalidomide, Dexamethasone

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

Drug: Carfilzomib
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
Other Names:
  • Kyprolis
  • Drug: Lenalidomide
    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
    Other Names:
  • Revlimid
  • Drug: Dexamethasone
    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
    Other Names:
  • Ozurdex
  • Drug: Lenalidomide
    After 8 cycles of combination carfilzomib, lenalidomide, and dexamethasone (CRd), patients may continue Lenalidomide for 12 cycles
    Other Names:
  • Revlimid
  • Drug: Lenalidomide
    After 12 cycles of extended dosing of Lenalidomide, patients may continue Lenalidomide for one year
    Other Names:
  • Revlimid
  • Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Serious and Non-serious Adverse Events [4 years and 9 months and 2 days]

      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

    1. Overall Response Rate [48.3 months]

      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.

    2. Progression Free Survival (PFS) at 48 Months [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.

    3. Percentage of Responders With Duration of Response (DOR) at 48 Months [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%.

    4. Overall Survival (OS) Rate [up to 6 months]

      OS is defined as the time of start of treatment to death from any cause.

    5. Cluster of Differentiation 138 (CD138) + Plasma Cells Gene Expression Profiling on Pre and Post Carfilzomib Exposure Bone Marrow Samples [Cycle 1 Day 1, an average of 28 days ± 2 days]

      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.

    6. Rate of Minimal Residual Disease (MRD) by Flow Cytometry [Day 100]

      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.

    7. 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 [up to 2 years]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 99 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    • INCLUSION CRITERIA:

    • Newly diagnosed patients with histologically confirmed multiple myeloma (MM) based on the following criteria:

    1. Clonal plasma cells in the bone marrow

    2. Measurable disease within the past 4 weeks defined by any one of the following:

    3. Serum monoclonal protein greater than or equal to 1.0 g/dL

    4. Urine monoclonal protein greater than 200 mg/24 hour

    5. Serum immunoglobulin free light chain greater than 10 mg/dL AND abnormal kappa/lambda ratio

    6. Evidence of underlying end organ damage attributed to underlying plasma cell proliferative disorder meeting at least one of the following:

    7. Hypercalcemia: serum calcium greater than or equal to 2.65 mmol/L

    8. Renal Insufficiency: serum creatinine greater than 2.0 mg/dL

    9. Anemia: hemoglobin value less than10 g/dL or 2 g/dL less than normal reference

    10. 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda Maryland United States 20892

    Sponsors and Collaborators

    • National Cancer Institute (NCI)
    • Celgene
    • Onyx Therapeutics, Inc.

    Investigators

    • Principal Investigator: Dickran Kazandjian, M.D., National Cancer Institute (NCI)

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Dickran Kazandjian, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01402284
    Other Study ID Numbers:
    • 110221
    • 11-C-0221
    First Posted:
    Jul 26, 2011
    Last Update Posted:
    Mar 2, 2021
    Last Verified:
    Feb 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Dickran Kazandjian, M.D., Principal Investigator, National Cancer Institute (NCI)
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone Therapy
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Period Title: Overall Study
    STARTED 45
    COMPLETED 31
    NOT COMPLETED 14

    Baseline Characteristics

    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Overall Participants 45
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    26
    57.8%
    >=65 years
    19
    42.2%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    60
    Sex: Female, Male (Count of Participants)
    Female
    18
    40%
    Male
    27
    60%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    45
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    2
    4.4%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    6
    13.3%
    White
    37
    82.2%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (Count of Participants)
    United States
    45
    100%
    Isotypes (percentage of participants) [Number]
    IgG kappa
    51
    113.3%
    IgG lambda
    16
    35.6%
    IgA kappa
    9
    20%
    IgA lambda
    9
    20%
    Free kappa
    9
    20%
    Free lambda
    4
    8.9%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 45
    Count of Participants [Participants]
    45
    100%
    2. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 45
    Number (95% Confidence Interval) [percentage of participants]
    97.8
    217.3%
    3. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 45
    Number (95% Confidence Interval) [percentage of participants]
    79.2
    176%
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 45
    Number (95% Confidence Interval) [percentage of participants]
    81.1
    180.2%
    5. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 45
    Number (95% Confidence Interval) [percentage of participants]
    89.5
    198.9%
    6. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Data were not collected due to lack of financial resources.
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 0
    7. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 45
    Number (95% Confidence Interval) [percentage of participants]
    44.4
    98.7%
    8. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    *Six patients withdrew from the study, four due to non-compliance and two to continue treatment at another institution. 'One patient refused to have a bone marrow biopsy procedure and one patient withdrew due to non-compliance. CR (n=0) after 8 cycles.
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    Measure Participants 45
    sCR/CR after 8 cycles
    46.7
    103.8%
    MRDnegCR after 8 cycles
    44.4
    98.7%
    nCR after 8 cycles
    20
    44.4%
    ≥VGPR after 8 cycles
    89
    197.8%
    ORR after 8 cycles
    97.8
    217.3%
    sCR after 8 cycles
    46.7
    103.8%
    sCR/CR after 1 year
    62.2
    138.2%
    sCR after 1 year
    60.0
    133.3%
    CR after 1 year
    2.2
    4.9%
    MRDnegCR after 1 year'
    53.5
    118.9%
    nCR after 1 year
    11.1
    24.7%
    ≥VGPR after 1 year
    89
    197.8%
    ORR after 1 year
    97.8
    217.3%
    sCR/CR after 2 years
    64.4
    143.1%
    sCR after 2 years
    62.2
    138.2%
    CR after 2 years
    2.2
    4.9%
    MRDnegCR after 2 years*
    46.2
    102.7%
    nCR after 2 years
    11.1
    24.7%
    ≥VGPR after 2 years
    91.1
    202.4%
    ORR after 2 years
    97.8
    217.3%

    Adverse Events

    Time Frame 4 years and 9 months and 2 days
    Adverse Event Reporting Description
    Arm/Group Title Carfilzomib, Lenalidomide, and Dexamethasone
    Arm/Group 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 Carfilzomib: 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 Lenalidomide: 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 Dexamethasone: Cycle 1: 20 mg oral or IV on days 2, 8, 9, 15, 16, 22,
    All Cause Mortality
    Carfilzomib, Lenalidomide, and Dexamethasone
    Affected / at Risk (%) # Events
    Total 3/45 (6.7%)
    Serious Adverse Events
    Carfilzomib, Lenalidomide, and Dexamethasone
    Affected / at Risk (%) # Events
    Total 19/45 (42.2%)
    Blood and lymphatic system disorders
    Anemia 4/45 (8.9%) 8
    Cardiac disorders
    Supraventricular tachycardia 1/45 (2.2%) 1
    Endocrine disorders
    Adrenal insufficiency 1/45 (2.2%) 2
    Gastrointestinal disorders
    Diarrhea 1/45 (2.2%) 1
    Enterocolitis infectious 2/45 (4.4%) 2
    General disorders
    Edema limbs 2/45 (4.4%) 2
    Fatigue 1/45 (2.2%) 3
    Fever 3/45 (6.7%) 3
    General disorders and administration site conditions - Other, night sweats/tremors 1/45 (2.2%) 1
    Death 2/45 (4.4%) 45
    Hepatobiliary disorders
    Cholecystitis 1/45 (2.2%) 1
    Immune system disorders
    Cytokine release syndrome 1/45 (2.2%) 1
    Infections and infestations
    Infections and infestations - Other, specify 1/45 (2.2%) 1
    Lung infection 3/45 (6.7%) 3
    Investigations
    Alanine aminotransferase increased 1/45 (2.2%) 1
    CD4 lymphocytes decreased 1/45 (2.2%) 1
    Creatinine increased 2/45 (4.4%) 3
    Lymphocyte count decreased 3/45 (6.7%) 4
    Neutrophil count decreased 1/45 (2.2%) 1
    Platelet count decreased 2/45 (4.4%) 4
    White blood cell decreased 1/45 (2.2%) 1
    Metabolism and nutrition disorders
    Dehydration 2/45 (4.4%) 3
    Hypercalcemia 1/45 (2.2%) 1
    Hyponatremia 2/45 (4.4%) 2
    Musculoskeletal and connective tissue disorders
    Myalgia 1/45 (2.2%) 1
    Nervous system disorders
    Presyncope 1/45 (2.2%) 1
    Psychiatric disorders
    Confusion 1/45 (2.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm 1/45 (2.2%) 1
    Dyspnea 5/45 (11.1%) 10
    Hiccups 1/45 (2.2%) 1
    Hypoxia 1/45 (2.2%) 1
    Pleural effusion 2/45 (4.4%) 2
    Respiratory failure 1/45 (2.2%) 1
    Vascular disorders
    Hypertension 1/45 (2.2%) 1
    Hypotension 2/45 (4.4%) 3
    Thromboembolic event 6/45 (13.3%) 6
    Other (Not Including Serious) Adverse Events
    Carfilzomib, Lenalidomide, and Dexamethasone
    Affected / at Risk (%) # Events
    Total 45/45 (100%)
    Blood and lymphatic system disorders
    Anemia 34/45 (75.6%) 148
    Febrile neutropenia 1/45 (2.2%) 1
    Cardiac disorders
    Atrioventricular block first degree 1/45 (2.2%) 1
    Cardiac disorders - Other, cardiac NOS 1/45 (2.2%) 1
    Electrocardiogram QT corrected interval prolonged 1/45 (2.2%) 1
    Heart failure 2/45 (4.4%) 2
    Palpitations 3/45 (6.7%) 3
    Sinus bradycardia 4/45 (8.9%) 5
    Sinus tachycardia 2/45 (4.4%) 3
    Ventricular arrhythmia 1/45 (2.2%) 1
    Ear and labyrinth disorders
    Otitis media 1/45 (2.2%) 1
    Tinnitus 1/45 (2.2%) 1
    Vertigo 1/45 (2.2%) 1
    Vestibular disorder 1/45 (2.2%) 1
    Endocrine disorders
    Hypothyroidism 2/45 (4.4%) 2
    Eye disorders
    Blurred vision 6/45 (13.3%) 6
    Cataract 1/45 (2.2%) 1
    Conjunctivitis 1/45 (2.2%) 1
    Dry eye 1/45 (2.2%) 1
    Eye disorders - Other, specify 8/45 (17.8%) 9
    Glaucoma 2/45 (4.4%) 2
    Papilledema 1/45 (2.2%) 2
    Gastrointestinal disorders
    Abdominal pain 3/45 (6.7%) 4
    Anal hemorrhage 1/45 (2.2%) 1
    Bloating 2/45 (4.4%) 2
    Constipation 25/45 (55.6%) 34
    Dental caries 1/45 (2.2%) 1
    Diarrhea 30/45 (66.7%) 51
    Dry mouth 6/45 (13.3%) 6
    Dyspepsia 6/45 (13.3%) 6
    Enterocolitis infectious 1/45 (2.2%) 1
    Gastric ulcer 1/45 (2.2%) 1
    Gastritis 3/45 (6.7%) 3
    Gastroesophageal reflux disease 8/45 (17.8%) 8
    Gastrointestinal disorders - Other, specify 1/45 (2.2%) 1
    Gingival pain 1/45 (2.2%) 1
    Lower gastrointestinal hemorrhage 1/45 (2.2%) 1
    Mucositis oral 1/45 (2.2%) 1
    Nausea 8/45 (17.8%) 10
    Rectal hemorrhage 1/45 (2.2%) 1
    Rectal pain 1/45 (2.2%) 1
    Toothache 2/45 (4.4%) 2
    Vomiting 4/45 (8.9%) 7
    General disorders
    Chills 5/45 (11.1%) 6
    Edema face 4/45 (8.9%) 5
    Edema limbs 17/45 (37.8%) 30
    Fatigue 28/45 (62.2%) 43
    Fever 12/45 (26.7%) 18
    Flu like symptoms 5/45 (11.1%) 5
    Gait disturbance 1/45 (2.2%) 1
    General disorders and administration site conditions - Other, Gastrointeritis 1/45 (2.2%) 1
    Generalized muscle weakness 1/45 (2.2%) 1
    Infusion related reaction 3/45 (6.7%) 5
    Injection site reaction 32/45 (71.1%) 51
    Irritability 4/45 (8.9%) 4
    Pain 19/45 (42.2%) 25
    Hepatobiliary disorders
    Gallbladder obstruction 1/45 (2.2%) 1
    Immune system disorders
    Allergic reaction 1/45 (2.2%) 1
    Infections and infestations
    Appendicitis 1/45 (2.2%) 1
    Bronchial infection 1/45 (2.2%) 1
    Infections and infestations - Other, specify 4/45 (8.9%) 4
    Laryngitis 1/45 (2.2%) 1
    Lung infection 2/45 (4.4%) 4
    Peripheral nerve infection 1/45 (2.2%) 1
    Rhinitis infective 1/45 (2.2%) 1
    Sinusitis 5/45 (11.1%) 6
    Skin infection 4/45 (8.9%) 4
    Tooth infection 1/45 (2.2%) 1
    Urinary tract infection 2/45 (4.4%) 3
    Vaginal infection 1/45 (2.2%) 1
    Injury, poisoning and procedural complications
    Bruising 2/45 (4.4%) 2
    Fall 2/45 (4.4%) 2
    Fracture 1/45 (2.2%) 1
    Radiation recall reaction (dermatologic) 1/45 (2.2%) 1
    Vascular access complication 1/45 (2.2%) 1
    Investigations
    Activated partial thromboplastin time prolonged 7/45 (15.6%) 9
    Alanine aminotransferase increased 36/45 (80%) 166
    Alkaline phosphatase increased 29/45 (64.4%) 67
    Aspartate aminotransferase increased 25/45 (55.6%) 71
    Blood bilirubin increased 23/45 (51.1%) 72
    CPK increased 10/45 (22.2%) 19
    Creatinine increased 18/45 (40%) 51
    Lipase increased 1/45 (2.2%) 2
    Lymphocyte count decreased 45/45 (100%) 438
    Lymphocyte count increased 1/45 (2.2%) 1
    Neutrophil count decreased 35/45 (77.8%) 207
    Platelet count decreased 42/45 (93.3%) 214
    Serum amylase increased 1/45 (2.2%) 1
    Weight loss 1/45 (2.2%) 1
    White blood cell decreased 38/45 (84.4%) 284
    Metabolism and nutrition disorders
    Anorexia 5/45 (11.1%) 7
    Dehydration 4/45 (8.9%) 5
    Hypercalcemia 10/45 (22.2%) 18
    Hyperglycemia 3/45 (6.7%) 3
    Hyperkalemia 9/45 (20%) 12
    Hypermagnesemia 23/45 (51.1%) 35
    Hypernatremia 26/45 (57.8%) 52
    Hyperuricemia 12/45 (26.7%) 25
    Hypoalbuminemia 42/45 (93.3%) 136
    Hypocalcemia 20/45 (44.4%) 36
    Hypokalemia 10/45 (22.2%) 19
    Hypomagnesemia 17/45 (37.8%) 40
    Hyponatremia 16/45 (35.6%) 33
    Hypophosphatemia 29/45 (64.4%) 79
    Musculoskeletal and connective tissue disorders
    Arthralgia 10/45 (22.2%) 10
    Back pain 7/45 (15.6%) 8
    Bone pain 2/45 (4.4%) 2
    Chest wall pain 11/45 (24.4%) 14
    Muscle weakness lower limb 1/45 (2.2%) 1
    Muscle weakness trunk 1/45 (2.2%) 1
    Musculoskeletal and connective tissue disorder - Other, specify 6/45 (13.3%) 9
    Myalgia 14/45 (31.1%) 19
    Neck pain 2/45 (4.4%) 2
    Non-cardiac chest pain 1/45 (2.2%) 1
    Pain in extremity 15/45 (33.3%) 17
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify 2/45 (4.4%) 2
    Nervous system disorders
    Cognitive disturbance 4/45 (8.9%) 4
    Concentration impairment 2/45 (4.4%) 2
    Dizziness 4/45 (8.9%) 4
    Dysarthria 1/45 (2.2%) 1
    Dysesthesia 1/45 (2.2%) 1
    Dysgeusia 9/45 (20%) 10
    Headache 15/45 (33.3%) 21
    Memory impairment 2/45 (4.4%) 2
    Nervous system disorders - Other, specify 1/45 (2.2%) 1
    Paresthesia 1/45 (2.2%) 1
    Peripheral motor neuropathy 1/45 (2.2%) 1
    Peripheral sensory neuropathy 22/45 (48.9%) 33
    Presyncope 2/45 (4.4%) 2
    Somnolence 1/45 (2.2%) 1
    Syncope 1/45 (2.2%) 1
    Tremor 9/45 (20%) 11
    Psychiatric disorders
    Agitation 1/45 (2.2%) 1
    Anxiety 3/45 (6.7%) 5
    Confusion 1/45 (2.2%) 1
    Depression 3/45 (6.7%) 3
    Insomnia 26/45 (57.8%) 30
    Libido decreased 1/45 (2.2%) 2
    Personality change 1/45 (2.2%) 1
    Psychiatric disorders - Other, Emotional lability 1/45 (2.2%) 1
    Suicidal ideation 1/45 (2.2%) 1
    Renal and urinary disorders
    Cystitis noninfective 1/45 (2.2%) 1
    Nocturia 1/45 (2.2%) 1
    Urinary frequency 2/45 (4.4%) 2
    Urinary incontinence 1/45 (2.2%) 1
    Urinary retention 1/45 (2.2%) 1
    Reproductive system and breast disorders
    Ejaculation disorder 1/45 (2.2%) 1
    Erectile dysfunction 1/45 (2.2%) 1
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 3/45 (6.7%) 3
    Bronchospasm 1/45 (2.2%) 1
    Cough 9/45 (20%) 12
    Dyspnea 20/45 (44.4%) 37
    Epistaxis 1/45 (2.2%) 1
    Hiccups 2/45 (4.4%) 3
    Hoarseness 6/45 (13.3%) 6
    Nasal congestion 3/45 (6.7%) 3
    Pericardial effusion 1/45 (2.2%) 1
    Pleural effusion 4/45 (8.9%) 4
    Pleuritic pain 1/45 (2.2%) 1
    Postnasal drip 1/45 (2.2%) 1
    Respiratory, thoracic and mediastinal disorders - Other, Rhinorrhea; Rt. Pleural density 2/45 (4.4%) 2
    Sore throat 3/45 (6.7%) 4
    Upper respiratory infection 30/45 (66.7%) 47
    Skin and subcutaneous tissue disorders
    Dry skin 3/45 (6.7%) 3
    Hyperhidrosis 1/45 (2.2%) 1
    Nail discoloration 2/45 (4.4%) 2
    Pruritus 6/45 (13.3%) 8
    Rash acneiform 2/45 (4.4%) 3
    Rash maculo-papular 27/45 (60%) 68
    Skin and subcutaneous tissue disorders - Other, specify 5/45 (11.1%) 5
    Skin hyperpigmentation 1/45 (2.2%) 1
    Skin ulceration 2/45 (4.4%) 2
    Vascular disorders
    Hematoma 2/45 (4.4%) 2
    Hot flashes 6/45 (13.3%) 7
    Hypertension 5/45 (11.1%) 16
    Hypotension 2/45 (4.4%) 3
    Phlebitis 2/45 (4.4%) 2
    Superficial thrombophlebitis 3/45 (6.7%) 3
    Thromboembolic event 5/45 (11.1%) 6
    Vascular disorders - Other, Raynaud's disorder 1/45 (2.2%) 1

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Dickran Kazandijian
    Organization National Cancer Institute
    Phone 301-480-8870
    Email kazandijiandg@mail.nih.gov
    Responsible Party:
    Dickran Kazandjian, M.D., Principal Investigator, National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT01402284
    Other Study ID Numbers:
    • 110221
    • 11-C-0221
    First Posted:
    Jul 26, 2011
    Last Update Posted:
    Mar 2, 2021
    Last Verified:
    Feb 1, 2021