Lenalidomide and Nivolumab in Treating Patients With Relapsed or Refractory Multiple Myeloma

Sponsor
Yvonne Efebera (Other)
Overall Status
Terminated
CT.gov ID
NCT03333746
Collaborator
National Cancer Institute (NCI) (NIH), American Cancer Society, Inc. (Other), Bristol-Myers Squibb (Industry)
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Study Details

Study Description

Brief Summary

This phase II trial studies how well lenalidomide and nivolumab work in treating patients with multiple myeloma that has come back or does not respond to treatment. Drugs used in chemotherapy, such as lenalidomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as nivolumab, may interfere with the ability of cancer cells to grow and spread. Giving lenalidomide and nivolumab may work better in treating patients with multiple myeloma.

Condition or Disease Intervention/Treatment Phase
  • Other: Laboratory Biomarker Analysis
  • Drug: Lenalidomide
  • Biological: Nivolumab
  • Other: Pharmacological Study
Phase 2

Detailed Description

PRIMARY OBJECTIVES:
  1. To determine the efficacy of nivolumab in combination with lenalidomide (Revlimid) in terms of overall response rate in patients with relapse/refractory multiple myeloma (MM).
OUTLINE:

Patients receive lenalidomide orally (PO) on days 1-21 and nivolumab intravenously (IV) over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Study Design

Study Type:
Interventional
Actual Enrollment :
1 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Lenalidomide in Combination With Nivolumab In Patients With Relapsed/Refractory Multiple Myeloma
Actual Study Start Date :
Mar 21, 2018
Actual Primary Completion Date :
Aug 13, 2018
Actual Study Completion Date :
Nov 16, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (lenalidomide, nivolumab)

Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: Lenalidomide
Given PO
Other Names:
  • CC-5013
  • CC5013
  • CDC 501
  • Revlimid
  • Biological: Nivolumab
    Given IV
    Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo
  • Other: Pharmacological Study
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. ORR (Overall Response Rate) [Up to 12 months]

      Will be assessed by IMWG response criteria. 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Up to 3 years]

      Will evaluate other clinical outcomes using the methods of Kaplan-Meier.

    2. Progression Free Survival (PFS) [Time from study entry until disease progression or death at trial closure for the per protocol population, assessed up to 3 years]

      Will evaluate other clinical outcomes using the methods of Kaplan-Meier.

    3. Time to Progression (TTP) [Time from start of treatment until the date he or she has progression or dies, assessed up to 3 years]

      Will be assessed.

    Other Outcome Measures

    1. Immunomonitoring of Lymphocytes Subsets Including Natural Killer (NK) Cell [Up to 3 years]

      Will be explored using graphical analyses as well as summarized quantitatively.

    2. Immunomonitoring of Lymphocytes Subsets Including T Cell [Up to 3 years]

      Will be explored using graphical analyses as well as summarized quantitatively.

    3. Pharmacokinetics: The Maximum Plasma Concentration (Cmax) [Screening, days 1 and 14 of each cycle]

      Will be assessed using Cmax for Nivolumab in combination with lenalidomide

    4. Pharmacodynamics Profiles:Time to Maximum Plasma Concentration (Tmax) [Screening, days 1 and 14 of each cycle]

      Will be assessed using Tmax for Nivolumab in combination with lenalidomide

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients with evidence of relapse or refractory disease as defined by International Myeloma Working Group (IMWG) criteria and measurable disease as defined by any of the following:

    • Serum m-protein >= 0.5 g/dl (>= 10 g/l)

    • Urine monoclonal protein >= 200 mg/24 hour(h)

    • Involved free light chain (FLC) level >= 10mg/dl (>= 100mg/l) and an abnormal serum free light chain ratio (< 0.26, or > 1.65)

    • Measurable biopsy proven plasmacytoma (should be measured within 28 days of initial investigational agent dosing)

    • Patients must have had at least 2 prior line of therapy

    • Patients must not have had progression of disease on lenalidomide 25 mg; stable disease on lenalidomide is permitted

    • Patient may be enrolled at any time from last line of therapy

    • Patients must have absolute neutrophil count (ANC) > 1000/uL

    • Platelets >= 75,000/uL, if plasma cell percentage on bone marrow biopsy aspirate or core is > 30%, platelet eligibility requirement will be adjusted to 60,000/ul

    • Total bilirubin =< 1.5 mg/dL

    • Alkaline phosphatase =< 3 X the upper limit of normal (ULN)

    • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2 X the ULN

    • Patients must have adequate renal function as evidenced by serum creatinine =< 2 mg/dL or calculated creatinine clearance of >= 40 ml/min within 14 days of registration using Modification of Diet in Renal Disease (MDRD) formula

    • Patient must be able to swallow capsule or tablet

    • Patients must provide informed consent

    • Patients must have a left ventricular ejection fraction > 30%, no uncontrolled arrhythmias or New York Heart Association class III-IV heart failure

    • Patients must have a Karnofsky performance status >= 70

    • A negative pregnancy test will be required for all women of child bearing potential; breast feeding is not permitted

    • Fertility requirements

    • Female patients with child bearing potential must have a negative pregnancy test at least 7 days before starting treatment drugs

    • Male patients must agree to use an adequate method of contraception for the duration of the study and for 7 months afterwards

    • Female patients must be either posy-menopausal, free from menses >= 2 years (yrs), surgically sterilized, willing to use two adequate barrier methods of contraception to prevent pregnancy, or agree to abstain from sexual activity starting from screening and for 5 months afterwards

    • Female patients of child bearing potential must agree to comply with the fertility and pregnancy test requirements dictated by the Rev-Assist program

    Exclusion Criteria:
    • Patients with peripheral neuropathy > Common Terminology Criteria for Adverse Events (CTCAE) grade 2

    • Patients receiving concurrent corticosteroids at the time protocol therapy is initiated other than for physiologic maintenance treatment

    • History of allergic reaction (including erythema nodosum) to lenalidomide

    • Concurrent use of complementary or alternative medicines that would confound the interpretation of toxicities and antitumor activity of the study drugs

    • Patients with contraindication to thromboprophylaxis

    • Unacceptable cardiac risk factors defined by any of the following criteria: patients with congenital long QT syndrome, any history of ventricular fibrillation or torsade de pointes, bradycardia defined as heart rate (HR) < 50 bpm, left ventricular ejection fraction < 30%

    • Patients who have received targeted or investigational agents within 2 weeks or within 5 half-lives of the agent and active metabolites (whichever is longer) and who have not recovered from side effects of those therapies

    • Patients who have undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from the side-effects of surgery

    • Patients with known positivity for human immunodeficiency virus (HIV), or hepatitis C; baseline testing for HIV and hepatitis C is not required

    • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention, other than non-melanoma skin cancer and carcinoma in situ of the cervix should not be enrolled; patients are not considered to have a ?currently active? malignancy if they have completed therapy for a prior malignancy, are disease free from a prior malignancy for >= 5 yrs and are considered by their physician to be less than 30% risk of relapse

    • Patients with active (untreated or relapsed) central nervous system (CNS) metastasis of the patient?s myeloma

    • Patients with a history of gastrointestinal surgery or other procedure that might, in the opinion of the investigator(s), interfere with the absorption or swallowing of the study drugs

    • Patients with any significant history of non-compliance to medical regimens or unwilling or unable to comply with the instructions given to them by the study staff

    • Any other medical condition, including mental illness or substance abuse, deemed by the investigator(s) to likely interfere with the patient?s ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210

    Sponsors and Collaborators

    • Yvonne Efebera
    • National Cancer Institute (NCI)
    • American Cancer Society, Inc.
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Yvonne Efebera, MD, Ohio State University Comprehensive Cancer Center

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Yvonne Efebera, Principal Investigator, Ohio State University Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03333746
    Other Study ID Numbers:
    • OSU-17160
    • NCI-2017-01653
    • P30CA016058
    First Posted:
    Nov 7, 2017
    Last Update Posted:
    May 30, 2019
    Last Verified:
    May 1, 2019
    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
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Period Title: Overall Study
    STARTED 1
    COMPLETED 0
    NOT COMPLETED 1

    Baseline Characteristics

    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Overall Participants 1
    Age (Count of Participants)
    <=18 years
    0
    0%
    Between 18 and 65 years
    0
    0%
    >=65 years
    1
    100%
    Sex: Female, Male (Count of Participants)
    Female
    0
    0%
    Male
    1
    100%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    Not Hispanic or Latino
    1
    100%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    0
    0%
    White
    1
    100%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    1
    100%

    Outcome Measures

    1. Primary Outcome
    Title ORR (Overall Response Rate)
    Description Will be assessed by IMWG response criteria. 95% binomial confidence intervals will also be calculated for the estimate of the proportion of responses.
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    data was not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0
    2. Secondary Outcome
    Title Overall Survival (OS)
    Description Will evaluate other clinical outcomes using the methods of Kaplan-Meier.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    data was not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0
    3. Secondary Outcome
    Title Progression Free Survival (PFS)
    Description Will evaluate other clinical outcomes using the methods of Kaplan-Meier.
    Time Frame Time from study entry until disease progression or death at trial closure for the per protocol population, assessed up to 3 years

    Outcome Measure Data

    Analysis Population Description
    data was not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0
    4. Secondary Outcome
    Title Time to Progression (TTP)
    Description Will be assessed.
    Time Frame Time from start of treatment until the date he or she has progression or dies, assessed up to 3 years

    Outcome Measure Data

    Analysis Population Description
    data was not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0
    5. Other Pre-specified Outcome
    Title Immunomonitoring of Lymphocytes Subsets Including Natural Killer (NK) Cell
    Description Will be explored using graphical analyses as well as summarized quantitatively.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    data not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0
    6. Other Pre-specified Outcome
    Title Immunomonitoring of Lymphocytes Subsets Including T Cell
    Description Will be explored using graphical analyses as well as summarized quantitatively.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    data not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0
    7. Other Pre-specified Outcome
    Title Pharmacokinetics: The Maximum Plasma Concentration (Cmax)
    Description Will be assessed using Cmax for Nivolumab in combination with lenalidomide
    Time Frame Screening, days 1 and 14 of each cycle

    Outcome Measure Data

    Analysis Population Description
    data not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0
    8. Other Pre-specified Outcome
    Title Pharmacodynamics Profiles:Time to Maximum Plasma Concentration (Tmax)
    Description Will be assessed using Tmax for Nivolumab in combination with lenalidomide
    Time Frame Screening, days 1 and 14 of each cycle

    Outcome Measure Data

    Analysis Population Description
    data not collected and analyzed
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    Measure Participants 0

    Adverse Events

    Time Frame Adverse Events were collected up to 8 months during the study was conducted.
    Adverse Event Reporting Description Toxicities were assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0.
    Arm/Group Title Treatment (Lenalidomide, Nivolumab)
    Arm/Group Description Patients receive lenalidomide PO on days 1-21 and nivolumab IV over 1 hour on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Lenalidomide: Given PO Nivolumab: Given IV Pharmacological Study: Correlative studies
    All Cause Mortality
    Treatment (Lenalidomide, Nivolumab)
    Affected / at Risk (%) # Events
    Total 0/1 (0%)
    Serious Adverse Events
    Treatment (Lenalidomide, Nivolumab)
    Affected / at Risk (%) # Events
    Total 0/1 (0%)
    Other (Not Including Serious) Adverse Events
    Treatment (Lenalidomide, Nivolumab)
    Affected / at Risk (%) # Events
    Total 1/1 (100%)
    Blood and lymphatic system disorders
    Anemia 1/1 (100%) 6
    Eye disorders
    Eye Hemorrhage 1/1 (100%) 1
    Gastrointestinal disorders
    Diarrhea-intermittent 1/1 (100%) 1
    Nausea 1/1 (100%) 1
    General disorders
    Fatigue 1/1 (100%) 4
    Hip Pain- Bilateral 1/1 (100%) 1
    Localized Edema (Bilateral Ankles) 1/1 (100%) 1
    Investigations
    Aspartate Aminotransferasae Increased 1/1 (100%) 2
    Blood Bilirubin Increased 1/1 (100%) 2
    Lymphocyte Count Decreased 1/1 (100%) 1
    Neutrophil Count Decreased 1/1 (100%) 1
    Platelet Count Decreased 1/1 (100%) 5
    White Blood Cell Decreased 1/1 (100%) 5
    Metabolism and nutrition disorders
    Anorexia 1/1 (100%) 1
    Hyperglycemia 1/1 (100%) 1
    Hypoalbuminemia 1/1 (100%) 1
    Hypocalcemia 1/1 (100%) 1
    Hypokalemia 1/1 (100%) 1
    Hypomagnesemia 1/1 (100%) 2
    Hyponatremia 1/1 (100%) 2
    Musculoskeletal and connective tissue disorders
    Generlized Weakness 1/1 (100%) 3
    Myalgia- Left Rib 1/1 (100%) 1
    Nervous system disorders
    Cognitive Disturbance 1/1 (100%) 1
    Psychiatric disorders
    Insomnia 1/1 (100%) 1
    Respiratory, thoracic and mediastinal disorders
    Cough (non-productive) 1/1 (100%) 1
    Dyspnea 1/1 (100%) 1
    Skin and subcutaneous tissue disorders
    Dry Skin- Bilateral Lower Extremities 1/1 (100%) 1

    Limitations/Caveats

    Study was discontinued due to FDA recommendations of the potential toxities of the combination of nivolumab with an immunemodulator(lenalidomide, pomalidomde)

    More Information

    Certain Agreements

    All Principal Investigators ARE 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. Yvonne Efebera
    Organization The Ohio State University Comprehensive Cancer Center
    Phone 614-293-7243 ext 1278
    Email Yvonne.Efebera@osumc.edu
    Responsible Party:
    Yvonne Efebera, Principal Investigator, Ohio State University Comprehensive Cancer Center
    ClinicalTrials.gov Identifier:
    NCT03333746
    Other Study ID Numbers:
    • OSU-17160
    • NCI-2017-01653
    • P30CA016058
    First Posted:
    Nov 7, 2017
    Last Update Posted:
    May 30, 2019
    Last Verified:
    May 1, 2019