Continuous Versus Intermittent Dosing Regimens for Pomalidomide in Relapsed/Refractory Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Pomalidomide
Intervention description: Comparison of different dosages and schedules of drug
Intervention MeSH terms: Pomalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: myeloma; multiple myeloma; pomalidomide; immunomodulatory

Summary:

      Lenalidomide has clinical activity in myeloma. The closely related compound, Pomalidomide,
      may have clinical activity in patients who have previously been treated with lenalidomide and
      who no longer respond to it. The mechanism of anti-tumor effects of these drugs has been
      attributed to several effects including anti-angiogenesis, immune activation, and
      anti-proliferative effects. Recent studies have suggested that these agents can mediate
      surprisingly rapid biologic effects on human monocytes and T cells. Our hypothesis is that
      the proximate effects of these drugs will be sensitive and quantitative surrogates of
      subsequent effects including activation of tumor antigen specific T cells as well as innate
      immune cells. Understanding the correlation between the pharmacodynamics of these effects
      with downstream activation using quantitative assays will facilitate the rational development
      of pomalidomide as immune-modulatory drug in diverse settings as well as its optimal
      development in myeloma therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Understand and voluntarily sign an informed consent form.

          -  Age ≥18 years at the time of signing the informed consent form.

          -  Able to adhere to the study visit schedule and other protocol requirements.

          -  Relapsed / Refractory Multiple Myeloma following at least two prior standard therapies
             including lenalidomide. Induction therapy followed by autologous stem cell
             transplantation (ASCT) is considered one regimen.

          -  Patients must be refractory to prior lenalidomide therapy. For the purpose of this
             protocol, refractory will be defined as history of progression on a regimen containing
             full or maximally tolerated dose of lenalidomide administered for a minimum of at
             least one complete cycle of therapy.

          -  All patients must have measurable disease defined as one or more of the following
             criteria:

               -  Serum monoclonal protein greater than 10 g/L, serum immunoglobulin free light
                  chain (FLC) more than 10 mg/dL and an abnormal FLC ratio, urine light-chain
                  excretion > 200 mg/24 h, measurable soft tissue plasmacytoma that has not been
                  irradiated, or greater than 30% plasma cells in bone marrow.

          -  All previous cancer therapy, including radiation, hormonal therapy and surgery, must
             have been discontinued at least 2 weeks prior to treatment in this study.

          -  Eastern Cooperative Oncology Group (ECOG ) performance status of ≤ 2 at study entry
             (see Appendix D).

          -  Laboratory test results within these ranges:

               -  Absolute neutrophil count ≥ 1.0 x 1000/microliter (uL)

               -  Platelet count ≥ 75 x 1000/uL

               -  Serum creatinine ≤ 2.5 mg/dL

               -  Total bilirubin ≤ 2 mg/dL

               -  aspartate aminotransferase (AST) (SGOT) and alanine aminotransferase (ALT) (SGPT)
                  ≤ 5 x upper limit of normal (ULN)

          -  Disease free of prior malignancies for ≥ 5 years with exception of currently treated
             basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" 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 milli-international unit (mIU)/mL
             within 10 - 14 days prior to and again within 24 hours of starting pomalidomide 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
             pomalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use
             a latex condom during sexual contact with a FCBP even if they have had a vasectomy.
             All patients must be counseled at a minimum of every 28 days about pregnancy
             precautions and risks of fetal exposure. See Appendix A and B: Risks of Fetal
             Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods, AND also
             Education and Counseling Guidance Document.

          -  Able to take aspirin (ASA) (81 mg) daily as prophylactic anticoagulation (patients
             intolerant to ASA may use warfarin or low molecular weight heparin).

        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. (Lactating females must agree not to breast feed
             while taking pomalidomide).

          -  Women of child-bearing potential who are unwilling to use a dual method of
             contraception; and men who are unwilling to use a condom.

          -  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 thalidomide or lenalidomide.

          -  The development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide, pomalidomide or similar drugs.

          -  Any prior use of pomalidomide.

          -  Concurrent use of other anti-cancer agents or treatments.

          -  Known positive for HIV or active infectious hepatitis, B or C.

          -  Grade 3 or 4 peripheral neuropathy