Pomalidomide in Gene Expression Profiling (GEP)-Defined High-risk Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Pomalidomide
Intervention description: Only enough CC-4047 for 1 cycle of therapy may be provided to the patient each cycle. Participants will receive CC-4047 4 mg/day for 21 days, every 28 days. Treatment will continue until disease recurrence or untoward toxicity.
Intervention MeSH terms: Pomalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 71.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Pomalidomide; multiple myeloma; relapsed

Summary:

      This is a phase II study, open-label, single institution trial of pomalidomide in
      GEP-defined, high-risk relapsing/refractory multiple myeloma. Prior therapy must have
      included lenalidomide. Patient accrual is 30 over a 2 year period.

      Primary objective:

        -  To determine progression-free survival (PFS) after initiation of pomalidomide therapy

      Secondary objective:

        -  To determine the response rate (CR, n-CR, VGPR) and duration of response after
           pomalidomide therapy.

        -  To determine gene expression profiling (GEP) changes exerted within 48 hours of
           initiation of daily pomalidomide dosing.

        -  To determine gene expression profiling (GEP) changes exerted within 48 hours of
           initiation 3 concurrent days of exposure to lenalidomide.

        -  To determine MRI- and PET-CT-defined CR in studies obtained at baseline and every 6
           month examinations.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant has multiple myeloma, relapsed or resistant to prior therapy.

          -  Participant has high-risk disease, as defined by any of the following:

               -  GEP risk score of > 0.66 OR

               -  Metaphase based abnormalities of 1q or 1p OR

               -  LDH > 360 U/L

          -  Participant has received prior therapy with lenalidomide-containing regimen and has
             been determined to be refractory, resistant, or relapsed.

          -  Participant has no significant peripheral neuropathy (< grade 3 by the most current
             NCI CTCAE version)

          -  Participant has adequate hematopoietic reserve as defined by platelet count ≥
             50,000/µL and ANC of > 1000/µL.

          -  Participant has adequate renal function as defined by serum creatinine < 2 mg/dL.

          -  Participant has adequate hepatic function, defined by serum Total bilirubin </= 1.5
             mg/dL and AST (SGOT) and ALT (SGPT) </= x ULN.

          -  Participant is 18 years of age or greater.

          -  Participant has not received anti-cancer therapy within 4 weeks prior to treatment on
             this study.

          -  Zubrod ≤ 2, unless solely due to symptoms of MM-related bone disease.

          -  Disease free of prior malignancies for >/= 5 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix or
             breast.

          -  Females of childbearing potential (FCBP)† must have a negative serum or urine
             pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to
             and again within 24 hours prior to starting lenalidomide or CC-4047 and must either
             commit to continued abstinence from heterosexual intercourse or begin TWO acceptable
             methods of birth control, one highly effective method and one additional effective
             method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide or
             CC-4047.

          -  All patients must be informed of the investigational nature of this study and must
             sign and give written voluntary consent in accordance with institutional and federal
             guidelines.

          -  Willing and able to take aspirin or alternate prophylactic anticoagulation.

        Exclusion Criteria:

          -  Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          -  Pregnant or breast feeding females.

          -  Men unwilling to use a condom (even if they have undergone a prior vasectomy) while
             having intercourse with any woman, while taking the drug and for 4 weeks after
             stopping treatment.

          -  Any condition, including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study or confounds
             the ability to interpret data from the study.

          -  Use of any other experimental drug or therapy within 28 days of baseline.

          -  Known hypersensitivity to lenalidomide.

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking lenalidomide, CC-4047 or similar drugs.

          -  Any prior use of CC-4047.

          -  Concurrent use of other anti-cancer agents or treatments.

          -  Known seropositive for or active viral infection with human immunodeficiency virus
             (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are
             seropositive because of hepatitis B virus vaccine are eligible.

          -  Active malignancy (exception of non melanoma skin cancer or in situ cervical or breast
             cancer).

          -  Active DVT or PE that has not been therapeutically anticoagulated.

          -  ≥ grade 3 peripheral neuropathy.