Sorafenib, Lenalidomide, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma
Condition: Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Intervention: dexamethasone; sorafenib tosylate; Lenalidomide
Intervention description: 20 mg orally Days 1, 8, 15, 22 of 28 day cycle; Phase I - dose escalating: 200mg once daily dose level -2, 200mg once daily dose level -1, 200mg once daily dose level 0, 200mg twice daily dose level 1, 200mg twice daily dose level 2, 400mg AM & 200mg PM daily dose level 2a, 400mg twice daily dose level 3 orally days 1-28 every 28 days until progression; Phase I - dose escalating: 5mg level -2, 10mg level -1, 15mg level 0, 15mg level 1, 25mg level 2, 25mg level 2a, 25mg level 3 orally days 1-21 every 28 days until progression
Intervention MeSH terms: Dexamethasone; Lenalidomide; Sorafenib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Maximum age: 120 Years
Healthy volunteers: No
Keywords: refractory multiple myeloma

Summary:

      RATIONALE: Sorafenib may stop the growth of cancer cells by blocking some of the enzymes
      needed for cell growth. Lenalidomide may stimulate the immune system in different ways and
      stop cancer cells from growing. Drugs used in chemotherapy, such as dexamethasone, work in
      different ways to stop the growth of cancer cells, either by killing the cells or by stopping
      them from dividing. Sorafenib and lenalidomide may also stop the growth of cancer cells by
      blocking blood flow to the cancer. Giving sorafenib together with lenalidomide and
      dexamethasone may kill more cancer cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib when
      given together with lenalidomide and dexamethasone and to see how well they work in treating
      patients with relapsed or refractory multiple myeloma.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosis of multiple myeloma

               -  Relapsed or refractory disease requiring treatment

          -  Measurable disease, as defined by at least 1 of the following:

               -  Serum monoclonal protein ≥ 1.0 g

               -  More than 200 mg of monoclonal protein in the urine on 24-hour electrophoresis

               -  Serum immunoglobulin free light chain ≥ 10 mg/dL AND abnormal serum
                  immunoglobulin kappa to lambda free light chain ratio

               -  Monoclonal bone marrow plasmacytosis ≥ 30% (i.e., evaluable disease)

          -  No known standard therapy that is potentially curative for the patient's disease

        PATIENT CHARACTERISTICS:

          -  ECOG performance status 0-2

          -  Life expectancy ≥ 12 weeks

          -  ANC ≥ 1,000/μL

          -  Platelet count ≥ 75,000/μL

          -  Hemoglobin ≥ 9 g/dL

          -  Direct bilirubin ≤ 1.5 times upper limit of normal (ULN)

          -  AST ≤ 3 times ULN (≤ 5 times ULN if the liver is involved)

          -  Creatinine ≤ 2.5 times ULN

          -  Patients with treated or untreated POEMS (Patient-Oriented Evidence That Matters)
             allowed, provided they satisfy the criteria for measurable disease

          -  No other prior malignancy within the past year except currently treated basal cell or
             squamous cell skin cancer, carcinoma in situ of the cervix or breast, or prostate
             cancer not requiring therapy

          -  No other active malignancy requiring treatment that would interfere with the
             assessments of response of the myeloma to protocol treatment

          -  INR < 1.5 OR PT/PTT ≤ 1.5 times ULN

               -  Patients receiving anticoagulation treatment with an agent such as warfarin or
                  heparin are allowed

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use 2 methods of effective contraception for 28 days prior,
             during, and for 28 days after discontinuation of lenalidomide

          -  Willing to provide research samples according to the test schedule

          -  No uncontrolled infection

          -  No NYHA classification III or IV heart disease

          -  No unstable angina (i.e., anginal symptoms at rest), new-onset angina (i.e., began
             within the past 3 months), or myocardial infarction within the past 6 months

          -  No uncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or
             diastolic pressure > 90 mm Hg, despite optimal medical management

          -  No thrombotic or embolic events within the past 6 months, including cerebrovascular
             accidents and transient ischemic attacks

          -  More than 4 weeks since prior pulmonary hemorrhage or other bleeding event > grade 2

          -  No serious nonhealing wound or ulcer

          -  More than 4 weeks since prior significant traumatic injury

          -  No known positivity for HIV infection or infectious hepatitis, type A, B, or C

          -  No known hypersensitivity to thalidomide or lenalidomide

          -  No prior development of erythema nodosum if characterized by a desquamating rash while
             taking thalidomide or similar drugs

          -  Able to take aspirin (325 mg) daily as prophylactic anticoagulation

        PRIOR CONCURRENT THERAPY:

          -  Recovered from prior chemotherapy, regardless of interval since last treatment

          -  Prior lenalidomide therapy allowed

          -  More than 4 weeks since prior experimental therapy

          -  More than 4 weeks since prior major surgery or open biopsy

          -  No concurrent enrollment in any other study involving a pharmacologic agent or
             investigative therapy (i.e., drug, biologic, immunotherapy approaches, gene therapy)
             whether for symptom control or therapeutic intent

          -  No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary
             therapy considered investigational

          -  No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (i.e., phenytoin,
             carbamazepine, and phenobarbital), rifampin, or Hypericum perforatum (St. John wort)