Treatment of POEMS Syndrome With Daratumumab
Condition: POEMS Syndrome
MeSH terms: POEMS Syndrome; Syndrome
Intervention: Daratumumab Injection
Intervention description: DARA is a human monoclonal antibody that specifically recognizes the CD38 molecule that is expressed at a high level in a variety of hematological malignancies, including myeloma cells.
DARA injection will be given with oral lenalidomide for up to 12 four week cycles.
Intervention MeSH terms: Daratumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This trial investigates the use of Daratumumab (DARA), an antibody directed at the human
      cluster of differentiation 38 (CD38) molecule, for the treatment of patients with
      Polyneuropathy, Organomegaly, Endocrinopathy, m Protein Component, Skin Changes (POEMS)
      syndrome. This trial will enroll ten subjects, who will complete 12 four-week cycles of DARA,
      in combination with the immunomodulatory drug (IMiD) lenalidomide. Objectives of this study
      include improvement in neuropathy and performance status, as well as improvement in
      laboratory values and survival.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have POEMS syndrome and meet the diagnostic criteria for POEMS syndrome
             as described in Appendix I.

          -  Both newly-diagnosed and relapsed POEMS syndrome will be eligible for inclusion.

          -  Patients must have a platelet count of ≥ 50,000/μL.

          -  Patients must be at least 18 years of age.

          -  Participants must have preserved renal function as defined by a serum creatinine level
             of < 3 mg/dL.

          -  Participants must have an ejection fraction by echocardiogram (ECHO) or multigated
             acquisition (MUGA) scan ≥ 40 percent.

          -  Eastern Cooperative Oncology Group ≥ 1,

          -  Overall Neuropathy Limitations Scale (ONLS) ≥ 1.

          -  Patients must have signed an institutional review board (IRB)-approved informed
             consent indicating their understanding of the proposed treatment and understanding
             that the protocol has been approved by the IRB.

        Exclusion Criteria:

          -  Documented allergy to lenalidomide, DARA, mannitol, other monoclonal antibodies or
             human proteins and mammalian-derived products.

          -  Prior treatment with DARA or other CD38 monoclonal antibodies

          -  Patients with central nervous system (CNS) Multiple Myeloma (MM) involvement.

          -  Patients who have received an investigational drug or device within 4 weeks prior to
             enrollment or received live attenuated vaccine within 4 weeks prior to enrollment.

          -  Poorly controlled hypertension, diabetes mellitus, or other serious medical illness or
             psychiatric illness that could potentially interfere with the completion of treatment
             according to this protocol.

          -  Poor performance status will not be an exclusion criterion since POEMS patients can be
             expected to have significant limitations.

          -  Patients must not have prior malignancy, except for adequately treated basal cell or
             squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
             patient has not received treatment for one year prior to enrollment. Other cancers
             will only be accepted if the patient's life expectancy exceeds five years.

          -  Male and Female subjects and their partners of reproductive potential may not
             participate unless they have agreed to use an effective contraceptive while on study
             and for 3 months after cessation of DARA.

          -  Males who are unwilling to abstain from sperm donation while on study and for 3 months
             after cessation of DARA.

          -  Females of childbearing potential must have a negative pregnancy test documented
             within one week of registration.

          -  Females who are pregnant or nursing women may not participate.

          -  Patients with POEMS syndrome, who do not have disseminated bone marrow (BM)
             involvement and have an isolated plasmacytoma; these patients should be considered for
             irradiation.

          -  Subjects has had major surgery within 2 weeks prior to enrollment.

          -  Clinically significant cardiac disease, including myocardial infarction within the
             past 6 months or unstable or uncontrolled conditions (e.g., unstable angina or
             congestive heart failure) or other cardiac disease which in the opinion of the
             investigator would constitute a hazard for participating in the study. Some cardiac
             dysfunction is expected in this population.

          -  Participant has known chronic obstructive pulmonary disease (COPD) [defined as a
             forced expiratory volume in 1 second (FEV1) <50% of predicted normal, forced vital
             capacity (FVC), etc.] and diffusion capacity (DLCO) < 40% of predicted.), known
             moderate or severe persistent asthma within the last 2 years or currently has
             uncontrolled asthma of any classification (controlled intermittent asthma or
             controlled mild persistent asthma is allowed). Exception may be granted if the
             principal investigator documents that the patient is a candidate for therapy since
             alternative therapies will at least have similar or not more toxicity.

          -  Participant with known or suspected COPD must have an FEV1 test during screening.

          -  Subjects who are seropositive for human immunodeficiency virus (HIV).

          -  Subjects who are seropositive for hepatitis B [defined by a positive test for
             hepatitis B surface antigen (HBsAg)]. Subjects with resolved infection [i.e., subjects
             who are HBsAg negative but positive for antibodies to hepatitis B core antigen
             (anti-HBc)] and/or antibodies to hepatitis B surface antigen (anti-HBs) must be
             screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B
             virus (HBV) DNA levels. Those who are PCR positive will be excluded. EXCEPTION:
             Subjects with serologic findings suggestive of HBV vaccination (anti-HBs positivity as
             the only serologic marker) AND a known history of prior HBV vaccination, do not need
             to be tested for HBV DNA by PCR.

          -  Subjects who are seropositive for hepatitis C except in the setting of a sustained
             virologic response (SVR), defined as aviremia at least 12 weeks after completion of
             antiviral therapy).