Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases
Condition: Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Metastatic Cancer; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Secondary Myelofibrosis; Unspecified Adult Solid Tumor, Protocol Specific
MeSH terms: Lymphoma; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasm Metastasis; Preleukemia; Nervous System Neoplasms; Central Nervous System Neoplasms; Plasmacytoma; Precancerous Conditions; Myelodysplastic Syndromes; Primary Myelofibrosis; Lymphoproliferative Disorders; Myeloproliferative Disorders; Syndrome
Study type: Interventional
Phase: Early Phase 1

Summary: 
      RATIONALE: Pemetrexed disodium may stop the growth of cancer cells by blocking some of the
      enzymes needed for cell growth. Studying samples of cerebrospinal fluid and blood from
      patients with cancer in the laboratory may help doctors learn how pemetrexed disodium works
      in the body and identify biomarkers related to cancer.

      PURPOSE: This clinical trial is studying the side effects and how well pemetrexed disodium
      works in treating patients with leptomeningeal metastases.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the cerebrospinal fluid (CSF):plasma ratio of pemetrexed disodium at different
           IV dose levels in patients with leptomeningeal metastases.

        -  Determine the safety of this drug in these patients.

        -  Determine the antitumor activity of this drug in these patients.

        -  Assess the role of CSF vascular endothelial growth factor and YKL 40 as markers of
           response and/or prognosis in these patients.

      OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes on day 1. Treatment repeats
      every 21 days in the absence of disease progression or unacceptable toxicity.

      Patients undergo lumbar puncture and blood collection prior to therapy and 30-60 minutes
      after the first dose of pemetrexed disodium for pharmacological studies. Patients with Ommaya
      reservoirs undergo cerebrospinal fluid (CSF) collection at baseline and 0.25, 0.50, 1, 2, 4,
      6 and 8.0 hours after pemetrexed disodium administration. CSF is then obtained once during
      each subsequent course of study treatment. CSF and blood are also evaluated for YKL 40 and
      vascular endothelial growth factor.

      After completion of study therapy, patients are followed every 2-3 months.

      PROJECTED ACCRUAL: A total of 15 patients will be accrued for this study.
    

Intervention name(s): Pemetrexed
Intervention type(s): Drug
Intervention description(s): Orally beginning at 500 mg/m2 every 3 weeks until disease progression
Other intervention name(s): Alimta; LY231514
Intervention MeSH terms: Pemetrexed
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: unspecified adult solid tumor, protocol specific; tumors metastatic to brain; leptomeningeal metastases; primary central nervous system non-Hodgkin lymphoma; primary central nervous system Hodgkin lymphoma; meningeal chronic myelogenous leukemia; relapsing chronic myelogenous leukemia; chronic eosinophilic leukemia; primary myelofibrosis; chronic neutrophilic leukemia; essential thrombocythemia; polycythemia vera; recurrent adult acute lymphoblastic leukemia; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); recurrent adult acute myeloid leukemia; previously treated myelodysplastic syndromes; secondary acute myeloid leukemia; acute undifferentiated leukemia; mast cell leukemia; recurrent adult T-cell leukemia/lymphoma; stage IV adult T-cell leukemia/lymphoma; T-cell large granular lymphocyte leukemia; atypical chronic myeloid leukemia, BCR-ABL negative; stage IV chronic lymphocytic leukemia; refractory chronic lymphocytic leukemia; chronic myelomonocytic leukemia; refractory hairy cell leukemia; prolymphocytic leukemia; stage IV mycosis fungoides/Sezary syndrome; recurrent mycosis fungoides/Sezary syndrome; stage IV cutaneous T-cell non-Hodgkin lymphoma; recurrent cutaneous T-cell non-Hodgkin lymphoma; adult grade III lymphomatoid granulomatosis; intraocular lymphoma; post-transplant lymphoproliferative disorder; refractory multiple myeloma; stage IV adult Hodgkin lymphoma; recurrent adult Hodgkin lymphoma; anaplastic large cell lymphoma; angioimmunoblastic T-cell lymphoma; Waldenstrom macroglobulinemia; stage IV adult Burkitt lymphoma; recurrent adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone 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; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; stage IV small lymphocytic lymphoma; recurrent small lymphocytic lymphoma; adult nasal type extranodal NK/T-cell lymphoma; accelerated phase chronic myelogenous leukemia; blastic phase chronic myelogenous leukemia; chronic phase chronic myelogenous leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; secondary myelofibrosis; AIDS-related peripheral/systemic lymphoma; AIDS-related primary CNS lymphoma; recurrent adult grade III lymphomatoid granulomatosis; stage III multiple myeloma; primary systemic amyloidosis; extramedullary plasmacytoma; monoclonal gammopathy of undetermined significance; isolated plasmacytoma of bone