Sorafenib and Everolimus in Treating Patients With Relapsed or Refractory Lymphoma or Multiple Myeloma
Condition: Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm
MeSH terms: Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Plasmacytoma
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Sorafenib and everolimus may stop the growth of cancer cells by blocking blood
      flow to the cancer and by blocking some of the enzymes needed for cell growth.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of sorafenib and
      everolimus and to see how well they work in treating patients with relapsed or refractory
      non-Hodgkin's lymphoma, Hodgkin's lymphoma, or multiple myeloma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the maximum tolerated dose (MTD) of sorafenib tosylate and everolimus in
           patients with relapsed or refractory non-Hodgkin's lymphoma, Hodgkin's lymphoma, or
           multiple myeloma.

        -  Determine the toxicity of this regimen in these patients.

        -  Evaluate the therapeutic activity of this regimen in these patients.

        -  Evaluate the pharmacokinetic interaction of this regimen.

        -  Correlate clinical (toxicity and/or tumor response or activity) effects with
           pharmacologic (pharmacokinetic/pharmacodynamic) parameters and/or biologic (correlative
           laboratory) results.

      OUTLINE: This is a multicenter, dose-escalation, phase I study followed by a phase II study.

        -  Phase I (closed to accrual as of 2/10/2009): Patients receive oral sorafenib tosylate
           and oral everolimus on days 1-28. Courses repeat every 28 days in the absence of disease
           progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of sorafenib tosylate and everolimus until
      the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that
      at which at least 2 out of at most 6 patients experience a Dose Limiting Toxicity (DLT).

        -  Phase II: Patients receive oral sorafenib tosylate twice daily and oral everolimus once
           daily at the MTD determined in phase I. Courses repeat every 28 days in the absence of
           disease progression or unacceptable toxicity.

      Blood and bone marrow are collected periodically during the study and analyzed by flow
      cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. Patients enrolled in
      phase I also undergo blood sample collection on days 8 and 15 during course 1 and on day 1 of
      each subsequent course for pharmacokinetic studies.

      After completion of study treatment, patients are followed every 6 months for 3 years.

      PROJECTED ACCRUAL: A total of 103 patients will be accrued for this study.
    

Intervention name(s): RAD001; Sorafenib
Intervention type(s): Drug; Drug
Intervention description(s): Phase I: Dose level 0: RAD001 5mg every other day; Dose level 1: RAD001 5mg every day; Dose level 2: RAD001 5mg every day; Dose level 3: RAD001 10mg every day; Phase II: RAD001 5mg every day;; Phase I: Dose level 0: Sorafenib 200 mg twice daily; Dose level 1: Sorafenib 200 mg twice daily; Dose level 2: Sorafenib 400 mg twice daily; Dose level 3: Sorafenib 400 mg twice daily; Phase II: Sorafenib 200 mg twice daily;
Other intervention name(s): Everolimus; sorafenib tosylate
Intervention MeSH terms: Everolimus; Sorafenib
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent adult Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; stage III multiple myeloma; refractory multiple myeloma; Waldenström macroglobulinemia; recurrent adult Burkitt lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent mantle cell lymphoma; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; cutaneous B-cell non-Hodgkin lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; recurrent mycosis fungoides/Sezary syndrome; recurrent adult grade III lymphomatoid granulomatosis