Clinical trial NCT00424242: Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases
Official title: A Pharmacokinetic Study of Pemetrexed in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: 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
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
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-01-18
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

* 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

PRIOR CONCURRENT THERAPY:

* 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

Primary outcomes:
measure: Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium
timeFrame: Every 6 weeks for assessment while on study.
measure: To determine whether there is any anti-tumor activity against LM with Pemetrexed.
timeFrame: Every six weeks.
measure: To determine the safety of Pemetrexed in patients with LM.
timeFrame: After every 2 doses approximately 6 weeks
measure: To assess the role of serum biomarkers in patients with LM.
timeFrame: Prior to dose one
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Robert H. Lurie Comprehensive Cancer Center at Northwestern University
state: Illinois
Study officials:
affiliation: Robert H. Lurie Cancer Center
name: Jeffrey J. Raizer, MD
role: PRINCIPAL_INVESTIGATOR
References: