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Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00424242
Recruitment Status : Completed
First Posted : January 18, 2007
Last Update Posted : September 8, 2021
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Brief 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.

Condition or disease Intervention/treatment Phase
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 Drug: Pemetrexed Early Phase 1

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases
Study Start Date : January 2007
Actual Primary Completion Date : January 2010
Actual Study Completion Date : September 2011

Resource links provided by the National Library of Medicine

Genetic and Rare Diseases Information Center resources: Multiple Myeloma Primary Myelofibrosis Myelodysplastic Syndromes B-cell Lymphoma Diffuse Large B-Cell Lymphoma Lymphosarcoma Primary Central Nervous System Lymphoma Burkitt Lymphoma Plasmablastic Lymphoma Lymphoma, Large-cell, Immunoblastic Follicular Lymphoma Hairy Cell Leukemia Chronic Lymphocytic Leukemia Myeloid Leukemia Chronic Myeloid Leukemia Acute Lymphoblastic Leukemia Lymphoblastic Lymphoma Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Mycosis Fungoides Cutaneous T-cell Lymphoma Sezary Syndrome Adult T-cell Leukemia/lymphoma Anaplastic Large Cell Lymphoma Extranodal Nasal NK/T Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Angioimmunoblastic Lymphadenopathy With Dysproteinemia Mantle Cell Lymphoma Chronic Myelomonocytic Leukemia Juvenile Myelomonocytic Leukemia Chronic Myeloproliferative Disorders Hodgkin Lymphoma Monoclonal Gammopathy of Undetermined Significance Waldenstrom Macroglobulinemia Plasmacytoma Polycythemia Vera Essential Thrombocythemia Aggressive NK Cell Leukemia T-cell Large Granular Lymphocyte Leukemia Marginal Zone Lymphoma AL Amyloidosis Chronic Neutrophilic Leukemia Post-transplant Lymphoproliferative Disease Leukemia, T-cell, Chronic Lymphomatoid Granulomatosis

Arm Intervention/treatment
Experimental: Escalating doses of Pemetrexed
Escalating doses of Pemetrexed beginning at 500 mg/m2
Drug: Pemetrexed
Orally beginning at 500 mg/m2 every 3 weeks until disease progression
Other Names:
  • Alimta
  • LY231514

Primary Outcome Measures :
  1. Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium [ Time Frame: Every 6 weeks for assessment while on study. ]
    Patients will have CSF collected approximately every 6 weeks for assessment while on study.

  2. To determine whether there is any anti-tumor activity against LM with Pemetrexed. [ Time Frame: Every six weeks. ]
    Patients will have a scan every six weeks to assess tumor response.

  3. To determine the safety of Pemetrexed in patients with LM. [ Time Frame: After every 2 doses approximately 6 weeks ]
    Adverse events will be collected every six weeks during patient visits.

  4. To assess the role of serum biomarkers in patients with LM. [ Time Frame: Prior to dose one ]
    Patients will have a one time blood draw to look at serum biomarkers prior to dose one.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 120 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of systemic malignancy (solid tumor or hematologic malignancy) or primary CNS lymphoma with leptomeningeal metastases (LM) as documented by MRI, cerebrospinal fluid, or both
  • Patients may have brain metastases in addition to LM
  • Patients with clinically significant interstitial fluid with effusion controlled by drainage are eligible


  • Karnofsky performance status 60-100%
  • Life expectancy > 2 months
  • Creatinine clearance ≥ 45 mL/min
  • Bilirubin < 1.5 times upper limit of normal (ULN)
  • Transaminases < 3.0 times ULN (5 times ULN for hepatic metastasis)
  • WBC > 3,000/mm³
  • Neutrophil count > 1,500/mm³
  • Platelet count > 100,000/mm³
  • Hemoglobin > 10 g/dL
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 3 months after completion of study treatment
  • Able to undergo lumbar puncture (i.e., no noncommunicating hydrocephalus or spinal block) or has an Ommaya reservoir in place
  • Able to take steroids, cyanocobalamin (vitamin B12), and folic acid
  • No other active cancer except nonmelanoma skin cancer or carcinoma in situ of the cervix
  • Patients with prior malignancies who are in complete remission and are off all therapy for that malignancy for ≥ 3 years are eligible
  • No significant medical or psychiatric illness that would interfere with study compliance


  • More than 2 weeks since prior radiotherapy and recovered
  • No concurrent radiotherapy
  • No nonsteroidal anti-inflammatory drugs (NSAIDs) or acetylsalicylic acid within 2 days before or after study treatment (5 days for long-acting NSAIDs)
  • No other concurrent cytotoxic chemotherapy
  • Concurrent hormonal or biological therapy allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00424242

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United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
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Principal Investigator: Jeffrey J. Raizer, MD Robert H. Lurie Cancer Center
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Responsible Party: Northwestern University Identifier: NCT00424242    
Other Study ID Numbers: NU 06C2
STU00004482 ( Other Identifier: Northwestern University IRB )
First Posted: January 18, 2007    Key Record Dates
Last Update Posted: September 8, 2021
Last Verified: September 2021
Keywords provided by Northwestern University:
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
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasm Metastasis
Nervous System Neoplasms
Central Nervous System Neoplasms
Precancerous Conditions
Myelodysplastic Syndromes
Primary Myelofibrosis
Lymphoproliferative Disorders
Myeloproliferative Disorders
Pathologic Processes
Neoplasms by Histologic Type
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Neoplastic Processes