Lenalidomide and Nivolumab in Treating Patients With Relapsed or Refractory Multiple Myeloma
Condition: Recurrent Plasma Cell Myeloma; Refractory Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Laboratory Biomarker Analysis; Lenalidomide; Nivolumab; Pharmacological Study
Intervention description: Correlative studies; Given PO; Given IV; Correlative studies
Intervention MeSH terms: Nivolumab; Lenalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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