Pembrolizumab, Lenalidomide, and Dexamethasone in Treating Patients With Newly Diagnosed Multiple Myeloma Eligible for Stem Cell Transplant
Condition: Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Dexamethasone; Laboratory Biomarker Analysis; Lenalidomide; Pembrolizumab
Intervention description: Given PO; Correlative studies; Given PO; Given IV
Intervention MeSH terms: Dexamethasone; Dexamethasone acetate; Pembrolizumab; Lenalidomide; Ichthammol; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well pembrolizumab, lenalidomide, and dexamethasone work in
      treating patients with newly diagnosed multiple myeloma that are eligible for stem cell
      transplant. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of
      cancer cells to grow and spread. Drugs used in chemotherapy, such as lenalidomide and
      dexamethasone, 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. Giving
      pembrolizumab, lenalidomide, and dexamethasone may work better in treating patients with
      multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis and previously untreated active multiple myeloma by International Myeloma
             Working Group (IMWG) diagnostic criteria for multiple myeloma

          -  Calculated creatinine clearance (using Cockcroft-Gault equation) >= 30 mL/min

          -  Absolute neutrophil count (ANC) >= 1000/mm^3

          -  Platelet count >= 75000/mm^3

          -  Hemoglobin >= 8.0 g/dL

          -  Total bilirubin =< 1.5 x upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

          -  Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 7 days
             should have elapsed from the last day of radiation

               -  NOTE: Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra,
                  pamidronate, or zoledronic acid is permitted; any additional agents not listed
                  must be approved by the principal investigator

          -  Measurable disease of multiple myeloma as defined by at least ONE of the following:

               -  Serum monoclonal protein >= 1.0 g/dL

               -  > 200 mg of monoclonal protein in the urine on 24 hour electrophoresis

               -  Serum immunoglobulin free light chain >= 10 mg/dL AND abnormal serum
                  immunoglobulin kappa to lambda free light chain ratio

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Provide written informed consent

          -  Negative pregnancy test done =< 7 days prior to registration, for women of
             childbearing potential only

          -  Willing to follow strict birth control measures as suggested by the study

               -  Female patients: If they are of childbearing potential, must agree to one of the
                  following:

                    -  Practice 2 effective methods of contraception, at the same time, from the
                       time of signing the informed consent form through 90 days after the last
                       dose of study drug, AND must also adhere to the guidelines of any
                       treatment-specific pregnancy prevention program, if applicable, OR

                    -  Agree to practice true abstinence when this is in line with the preferred
                       and usual lifestyle of the subject (periodic abstinence [e.g., calendar,
                       ovulation, symptothermal, post-ovulation methods] and withdrawal are not
                       acceptable methods of contraception)

               -  Male patients: even if surgically sterilized (i.e., status post-vasectomy), must
                  agree to one of the following:

                    -  Agree to practice effective barrier contraception during the entire study
                       treatment period and through 120 days after the last dose of study drug, OR

                    -  Must also adhere to the guidelines of any treatment-specific pregnancy
                       prevention program, if applicable, OR

                    -  Agree to practice true abstinence when this is in line with the preferred
                       and usual lifestyle of the subject (periodic abstinence [e.g., calendar,
                       ovulation, symptothermal, post-ovulation methods] and withdrawal are not
                       acceptable methods of contraception)

          -  Willing to return to enrolling institution for follow-up (during the active monitoring
             phase of the study)

          -  Willing to provide consent to Institutional Review Board (IRB) number (#) 521-93 and
             provide research tissue and blood specimens

        Exclusion Criteria:

          -  Monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma

          -  Prior cytotoxic chemotherapy or corticosteroids for the treatment of multiple myeloma

               -  NOTE: Prior corticosteroid use for the treatment of non-malignant disorders is
                  permitted

          -  Diagnosed or treated for another malignancy =< 2 years before study enrollment or
             previously diagnosed with another malignancy and have any evidence of residual
             disease.

               -  NOTE: Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
                  not excluded if they have undergone complete resection

          -  Any of the following:

               -  Pregnant women

               -  Nursing women

               -  Men or women of childbearing potential who are unwilling to employ adequate
                  contraception

          -  Other co-morbidity which would interfere with patient's ability to participate in
             trial, e.g. uncontrolled infection, uncompensated heart or lung disease

          -  Other concurrent chemotherapy or any ancillary therapy considered investigational

               -  NOTE: Bisphosphonates are considered to be supportive care rather than therapy,
                  and are thus allowed while on protocol treatment

          -  Peripheral neuropathy >= grade 3 on clinical examination or grade 2 with pain during
             the screening period

          -  Major surgery =< 14 days prior to study registration

          -  Radiotherapy =< 14 days prior to registration

               -  NOTE: If the involved field is small, 7 days will be considered a sufficient
                  interval between treatment and administration of study drugs

          -  Participation in any other clinical trials with other investigational agents not
             included in this trial, =< 21 days prior to registration

          -  Active autoimmune disease that has required systemic treatment in the past 2 years
             (i.e. with use of disease modifying agents, corticosteroids, or immunosuppressive
             drugs)

               -  NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic
                  corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.)
                  is not considered a form of systemic treatment

          -  Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis

          -  Active infection requiring systemic therapy

          -  History or current evidence of any condition, therapy, or laboratory abnormality that
             might confound the results of the trial, interfere with the subject's participation
             for the full duration of the trial, or is not in the best interest of the subject to
             participate, in the opinion of the treating investigator

          -  Known psychiatric or substance abuse disorders that would interfere with cooperation
             with the requirements of the trial

          -  Is pregnant or breastfeeding, or expecting to conceive or father children within the
             projected duration of the trial, starting with the pre-screening or screening visit
             through 120 days after the last dose of trial treatment

          -  Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent

          -  Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

          -  Known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
             hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
             detected)

          -  Received a live vaccine =< 30 days of planned start of study therapy