Pembrolizumab Cyclophosphamide and Lenalidomide for Patients With Relapsed Multiple Myeloma

Inclusion Criteria: * Be willing and able to provide written informed consent for the trial and willing to follow the trial protocol. * Be 18 years of age or greater on day of signing informed consent. * Measurable disease with at least one of the following: * Paraprotein greater than or equal to 5g/L * Serum free light chains greater than or equal to 100mg/L with abnormal radio for light chain only * myeloma * Bence Jones protein greater than or equal to 200mg/24hr * Have relapsed MM following 1 or more prior lines of therapy. * Have achieved a partial response (PR or better based on investigator's determination of response by the International Myeloma Working Group (IMWG) criteria) to at least one prior regimen * Have a performance status of 0-1 on the ECOG Performance Scale. * Demonstrate adequate organ function as defined below, all screening laboratory tests are to be performed within 10 days prior to registration: Haematological * Absolute neutrophil count greater than or equal to 1.0 x109 /L. Growth factor support is not permitted within 7 days prior to assessment * Platelet count greater than or equal to 75 x 109/L. Platelet support is not permitted within 7 days prior to assessment. * Haemoglobin greater than or equal to 90 g/L. Blood support is not permitted within 7 days prior to assessment. Renal * Serum creatinine or, measured or calculated creatinine clearance less than or equal to 1.5 x local ULN OR Creatinine Clearance greater than or equal to 60 mL/min for participant with creatinine levels greater than 1.5 x local ULN Hepatic * Serum bilirubin less than or equal to 1.5 x local ULN OR direct bilirubin less than or equal to local ULN for participants with total bilirubin levels greater than 1.5 x local ULN * Aspartate transaminase (AST) or Alanine transaminase (ALT) less than or equal to 2.5 x local ULN * Albumin greater than or equal to 2.5 mg/dL (25 g/L) Coagulation * International Normalized Ratio (INR) or Prothrombin Time (PT) less than or equal to1.5 x local ULN, unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants • The standard Celgene Revlimid REMS program must be followed for all participants taking part in the trial and followed accordingly. In addition the following must also be followed: * Female participant of childbearing potential should have a negative urine or serum pregnancy test. Female participants of childbearing potential must be willing to use adequate methods of contraception, from 4 weeks prior to the start of treatment, until 120 days after the last dose of trial medication, and for all interruptions in dosing during the trial. * Male participants of childbearing potential must agree to use adequate methods of contraception from 4 weeks prior to the start of treatment, until 120 days after the last dose of trial medication, and for all interruptions in dosing during the trial. * All participants must agree to refrain from donation blood while on trial drug, including during dose interruptions and for 120 days after discontinuation from this trial Exclusion Criteria * Those with non-measurable disease, solitary bone or solitary extramedullary plasmacytoma, plasma cell leukaemia, POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) * Is currently participating and receiving trial therapy, or has participated in a trial of an investigational agent and received trial therapy or used an investigational device within 28 days prior to the first dose of trial treatment. * Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 14 days prior to the first dose of trial treatment. Steroids for myeloma disease control must be stopped 14 days prior to the first dose of trial treatment. * If previously treated with a lenalidomide-containing regimen, the participant is excluded if: * Discontinued due to any adverse event related to prior lenalidomide (history of thromboembolism due to lenalidomide is allowed if participant is anticoagulated) * If the participant was intolerant to lenalidomide. * If the participant was refractory to any dose of lenalidomide. Refractory to lenalidomide is defined either: Participant had disease progression within 60 days after the last dose of lenalidomide; or Whose disease is non-responsive whilst on lenalidomide. Non-responsive disease is defined as either not achieving at least an minimal response (MR) or progressive disease (PD) whilst on lenalidomide. * Any of the following prior treatments: * Has had a prior allogenic stem cell transplant. Previous autologous stem cell transplantation is permitted greater than or equal to 3 months prior to the first dose of trial treatment. * Previous therapy with pembrolizumab or has received prior therapy with an anti-PD-1, L1 or L2 inhibitor. * Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of trial treatment or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. o Has had prior chemotherapy, targeted small molecule therapy, therapeutic radiation therapy within 2 weeks prior to the first dose of trial treatment or who has not recovered (i.e., less than or equal to Grade 1 or at baseline) from adverse events due to a previously administered agent. Participants with less than ore equal to Grade 2 neuropathy are an exception to this criterion and may participant in the trial. * Treatment with plasmapheresis within 4 weeks prior to the first dose of trial treatment. * Palliative radiotherapy for pain control and bisphosphonates are permitted * A known hypersensitivity or intolerance to cyclophosphamide or lenalidomide or any of its excipients. * If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. * Unable to tolerate thromboembolic prophylaxis including, as clinically indicated, aspirin, warfarin or low-molecular weight heparin. * Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer. * Has known active central nervous system (CNS) myeloma and/or carcinomatous meningitis. Participants with previously treated CNS myeloma may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging CNS disease, and are not using steroids for at least 14 days prior to the first dose of trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. * Has 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). 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. * Significant cardiac disease as determined by the investigator including: * Known or suspected cardiac amyloidosis * Congestive heart failure of Class III or IV of the New York Heart Association (NYHA) classification; * Uncontrolled angina, hypertension or arrhythmia * Myocardial infarction in past 6 months * Any uncontrolled or severe cardiovascular disease * Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial. * Has an active infection requiring systemic therapy. * Has a known history of active TB (Bacillus Tuberculosis) * Has known history of, or any evidence of active, non-infectious pneumonitis. * Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). * Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). * Has received a live vaccine within 28 days prior to the first dose of trial treatment. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed. * Is pregnant or breastfeeding, or expecting to conceive or father children within the duration of their involvement in the trial, starting with the 4 weeks prior to starting trial treatment, during trial treatment including during any treatment interruptions until 120 days after the last dose of trial treatment. * Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.