Phase 2 Multi-center Study of Anti-PD-1 During Lymphopenic State After HDT/ASCT for Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Autologous Stem Cell Transplant; Melphalan; Lenalidomide; MK-3475
Intervention description: 140-200 mg/m^2; 5-15 mg/day starting 45-90 days post-transplant; 200 mg/day every 3 weeks starting day +14 post-transplant for a total of 9 doses.
Intervention MeSH terms: Pembrolizumab; Lenalidomide; Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Multiple Myeloma; Anti-PD-1; Pembrolizumab; Post-transplant; Maintenance

Summary:

      Multiple myeloma (MM) is a common incurable blood cancer causing debilitating symptoms-bone
      pain, kidney failure, low blood counts and infection. Chemotherapy outcomes are disappointing
      due to short-term response and long-term toxicities.

        1. Studies showed these patients have weak immune against MM due to the immune checkpoint
           mediated by the PD1/PD-L1 interaction between immune cells and MM. Anti-PD-1 antibody
           (anti-PD1) disrupts this interaction, thus unleashing immune cell function and leading
           to killing of MM cells.

        2. Studies further showed enhancement of this "unleash" after autologous transplant and
           better MM control by anti-PD1 when used after transplant.

        3. Anti-PD1 has been extensively studied in patients with other cancers. It is very safe
           and effective and has been FDA-approved. Complications are of mild degree and easy to
           manage successfully in out-patient setting. Severe complications are rare.

      Thus, investigators proposed an efficacy study of anti-PD1 treatment after transplant to
      improve MM treatment outcomes. This was a collaborative study with Medical College of
      Wisconsin (headquarter of Center for International blood and Marrow Transplant Research).
      Investigators hypothesized that anti-PD1 treatment would increase the MM response and the MM
      control duration when added to the standard MM treatment after transplant. Anti-PD1 was given
      at the dose and interval, which had been studied previously (200 mg intravenous injection
      every 3 weeks) between 2 weeks until 6 months after transplant. Subjects were monitored
      closely during and after anti-PD1 therapy until at least 1 year post transplant. Late
      complications were followed for 3 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects with MM (Multiple Myeloma) of any stage

          -  Has no Progressive Disease (PD) AND has suboptimal response with primary therapy

          -  Has measurable disease

          -  Has no prior hematopoietic stem cell transplant of any type

          -  Has performance status of 0 or 1 (Eastern Cooperative Oncology, ECOG, Performance
             Scale)

          -  Has had a successful peripheral blood stem cell collection with G-CSF (Filgrastim) +/-
             Plerixafor (Mozobil) only

          -  Be willing and able to provide written informed consent

          -  Female subjects of child bearing age should have negative urine or serum pregnancy
             test

          -  Female subjects of child bearing age must be willing to use 2 methods of birth control
             or be surgically sterile or abstain from heterosexual activity

          -  Male subjects must agree to use an adequate method of contraception

          -  Subject must be able to swallow capsules

          -  Must demonstrate adequate organ function

        Exclusion Criteria:

          -  Has history of repeat infections, amyloidosis, hyperviscosity, plasma cell leukemia,
             POEMS syndrome, Waldenstrom's macroglobulinemia, non-secretory multiple myeloma, or
             IgM myeloma

          -  Has known CNS (Central Nervous System) involvement or history of resolved CNS
             involvement

          -  Has an active autoimmune disease or history of autoimmune disease that requires
             systemic treatment with steroids of immunosuppressive agents.

          -  Has active, non-infectious pneumonitis

          -  Has diagnosis of immunosuppressive disorder or on immunosuppressive therapy within 7
             days of transplant admission

          -  Is currently participating in or has previously participated in the study of an
             investigational drug/device within 4 weeks of transplant admission

          -  Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or CTLA-4

          -  Has had prior monoclonal antibody, chemotherapy, small molecule therapy, or radiation
             within 2 weeks of transplant admission

          -  Has not recovered from adverse events due to previously administered agent

          -  Must be free of additional malignancy for at least 5 years

          -  Has an active infection requiring systemic therapy

          -  Has known psychiatric or substance abuse disorders that would interfere with
             requirements of the study

          -  Is pregnant or breastfeeding or expecting to conceive

          -  Has known HIV, Hepatitis B, or Hepatitis C infection

          -  Has clinically significant coagulopathy

          -  Has known symptomatic heart failure, unstable angina pectoris, or cardiac arrhythmia

          -  Has received any type of hematopoietic cell transplant

          -  Has received a live vaccine within 30 days of transplant admission

          -  Is or has an immediate family member whos is investigational site or sponsor staff
             directly involved with this study