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Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

Primary Purpose

Brain and Central Nervous System Tumors, Chronic Myeloproliferative Disorders, Leukemia

Status

Completed

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Pemetrexed

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Escalating doses of Pemetrexed

Arm Description

Escalating doses of Pemetrexed beginning at 500 mg/m2

Outcomes

Primary Outcome Measures

Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium

Patients will have CSF collected approximately every 6 weeks for assessment while on study.

To determine whether there is any anti-tumor activity against LM with Pemetrexed.

Patients will have a scan every six weeks to assess tumor response.

To determine the safety of Pemetrexed in patients with LM.

Adverse events will be collected every six weeks during patient visits.

To assess the role of serum biomarkers in patients with LM.

Patients will have a one time blood draw to look at serum biomarkers prior to dose one.

Secondary Outcome Measures

Full Information

NCT ID

NCT00424242

First Posted

January 16, 2007

Last Updated

September 3, 2021

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00424242

Brief Title

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

2. Study Status

Record Verification Date

September 2021

Overall Recruitment Status

Completed

Study Start Date

January 2007 (undefined)

Primary Completion Date

January 2010 (Actual)

Study Completion Date

September 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Escalating doses of Pemetrexed

Arm Type

Experimental

Arm Description

Escalating doses of Pemetrexed beginning at 500 mg/m2

Intervention Type

Drug

Intervention Name(s)

Pemetrexed

Other Intervention Name(s)

Alimta, LY231514

Intervention Description

Orally beginning at 500 mg/m2 every 3 weeks until disease progression

Primary Outcome Measure Information:

Title

Correlation of cerebrospinal fluid levels with plasma levels of different doses of pemetrexed disodium

Description

Patients will have CSF collected approximately every 6 weeks for assessment while on study.

Time Frame

Every 6 weeks for assessment while on study.

Title

To determine whether there is any anti-tumor activity against LM with Pemetrexed.

Description

Patients will have a scan every six weeks to assess tumor response.

Time Frame

Every six weeks.

Title

To determine the safety of Pemetrexed in patients with LM.

Description

Adverse events will be collected every six weeks during patient visits.

Time Frame

After every 2 doses approximately 6 weeks

Title

To assess the role of serum biomarkers in patients with LM.

Description

Patients will have a one time blood draw to look at serum biomarkers prior to dose one.

Time Frame

Prior to dose one

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey J. Raizer, MD

Organizational Affiliation

Robert H. Lurie Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611-3013

Country

United States

12. IPD Sharing Statement

Learn more about this trial

Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

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