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Pemetrexed and Temozolomide in Treating Patients With Relapsed Primary Central Nervous System Lymphoma （PCNSL）

Primary Purpose

Central Nervous System Tumors

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pemetrexe
Temozolomide
Sponsored by
Rongjie Tao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

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

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Histologically confirmed primary CNS lymphoma.
  • ECOG (Eastern Cooperative Oncology Group) Performance status of 0-1.
  • Positive cerebrospinal fluid (CSF) cytology or immunohistochemical diagnosis of CSF monoclonality with or without measurable intracranial disease.
  • Measurable (greater than 1 cm in diameter) tumor by CT scan or MRI.
  • Progressed during first-line chemotherapy and/or radiotherapy OR relapsed after initial successful treatment.
  • No systemic lymphoma by CT scan of the chest, abdomen, and pelvis with contrast.
  • No leptomeningeal lymphoma by lumbar puncture for CNS cytology/flow cytometry.
  • No ocular lymphoma by slit lamp examination.
  • Must have adequate organ function as defined by the protocol: Adequate renal function: serum creatinine ≤ 1.5 mg/dl and/or calculated creatinine clearance ≥ 60 ml/min; Adequate hepatic function: bilirubin level ≤ 1.5 x ULN, ASAT & ALST ≤ 1.5 x ULN.Adequate bone marrow reserves: neutrophil (ANC) count ≥ 1500 /mm^3, platelet count ≥ 100,000 /mm^3, hemoglobin ≥ 9 g/dl.
  • Age >/= 18 and </= 75 years.
  • Signed written informed consent prior to study entry.

Exclusion Criteria:

  • Patients with human immunodeficiency virus seropositivity and systemic lymphoma manifestation.
  • Serious uncontrolled concurrent illness.
  • Previous brain radiotherapy, systemic chemotherapy.
  • Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol.
  • Any evidence of prior exposure to Hepatitis B virus.
  • Unable to comprehend the study requirements or who are not likely to comply with the study parameters.
  • Pregnant (confirmed by serum or urine β-HCG) or lactating.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Pemetrexed and Temozolomide

    Arm Description

    Patients with relapsed PCNSL patients were treated with high-dose pemetrexed (900mg/m2) and temozolomide (200mg/m² day 1-5, 28 day cycle).

    Outcomes

    Primary Outcome Measures

    complete response (CR)
    Contrast MRI was performed to assess treatment response at 3-month interval for 2 years and thereafter every 6 months for next 3-5 years and then annually. The treatment response was reassessed according to International PCNSL Collaborative Group' criteria[1]. [1] Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. International Primary CNS Lymphoma Collaborative Group. J Clin Oncol 2005;23:5034-43.

    Secondary Outcome Measures

    Failure-free survival (PFS)
    Contrast MRI was performed to assess treatment response. PFS was defined as the time from initial diagnosis until disease progression. PFS and median PFS were analyzed using the Kaplan-Meier product limit curve.
    Toxicity
    Toxicity was graded according to the Word Health Organization (WHO) classification. For example:hematotoxicity,nausea,fatigue, abnormal liver function, alopecia, peripheral nerve damage, and constipation et al.
    Overall response rate (ORR)
    The disease control rate,This is the equivalent to Overall response rate, was (CR+ PR+SD).CR:complete respons; PR:partial response; SD:stable disease.

    Full Information

    First Posted
    November 4, 2013
    Last Updated
    November 8, 2013
    Sponsor
    Rongjie Tao
    Collaborators
    National Natural Science Foundation of China
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01985451
    Brief Title
    Pemetrexed and Temozolomide in Treating Patients With Relapsed Primary Central Nervous System Lymphoma （PCNSL）
    Official Title
    Phase II Trial of Pemetrexed and Temozolomide in Treating Patients With Relapsed PCNSL
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    November 2013
    Overall Recruitment Status
    Unknown status
    Study Start Date
    March 2013 (undefined)
    Primary Completion Date
    March 2015 (Anticipated)
    Study Completion Date
    March 2015 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Rongjie Tao
    Collaborators
    National Natural Science Foundation of China

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    In this trial, we will treat relapsed PCNSL with temozolomide, pemetrexed. Our objective was to assess our treatment strategies' availability based on response rates, progression-free survival (PFS), median PFS, and toxicity.
    Detailed Description
    The best reported outcomes of PCNSL treatment are high-dose methotrexate-based chemotherapy combined with whole-brain radiation therapy (WBRT). Despite aggressive therapy, however, nearly 50% of patients will relapse within 24 months of diagnosis. Furthermore, the application of high-dose methotrexate-based regimen is complex, needing be hydrated, alkalified and detoxified, and treatment-related toxicity mortality is severe. In an attempt to improve upon these poor results and reduce treatment-related side effects, we will treat about 15-20 relapsed PCNSL patients who was fail in high-dose methotrexate-based chemotherapy. Our objective is to assess our treatment strategies' availability based on response rates, progression-free survival (PFS), median PFS, and toxicity.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Central Nervous System Tumors
    Keywords
    Lymphoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    15 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Pemetrexed and Temozolomide
    Arm Type
    Experimental
    Arm Description
    Patients with relapsed PCNSL patients were treated with high-dose pemetrexed (900mg/m2) and temozolomide (200mg/m² day 1-5, 28 day cycle).
    Intervention Type
    Drug
    Intervention Name(s)
    Pemetrexe
    Other Intervention Name(s)
    Alimta
    Intervention Description
    Patients with relapsed PCNSL patients were treated with high-dose pemetrexed (900mg/m²).
    Intervention Type
    Drug
    Intervention Name(s)
    Temozolomide
    Other Intervention Name(s)
    Temodal
    Intervention Description
    Patients with relapsed PCNSL patients were treated with temozolomide (200mg/m² day 1-5,28).
    Primary Outcome Measure Information:
    Title
    complete response (CR)
    Description
    Contrast MRI was performed to assess treatment response at 3-month interval for 2 years and thereafter every 6 months for next 3-5 years and then annually. The treatment response was reassessed according to International PCNSL Collaborative Group' criteria[1]. [1] Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. International Primary CNS Lymphoma Collaborative Group. J Clin Oncol 2005;23:5034-43.
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Failure-free survival (PFS)
    Description
    Contrast MRI was performed to assess treatment response. PFS was defined as the time from initial diagnosis until disease progression. PFS and median PFS were analyzed using the Kaplan-Meier product limit curve.
    Time Frame
    2 years
    Title
    Toxicity
    Description
    Toxicity was graded according to the Word Health Organization (WHO) classification. For example:hematotoxicity,nausea,fatigue, abnormal liver function, alopecia, peripheral nerve damage, and constipation et al.
    Time Frame
    2 years
    Title
    Overall response rate (ORR)
    Description
    The disease control rate,This is the equivalent to Overall response rate, was (CR+ PR+SD).CR:complete respons; PR:partial response; SD:stable disease.
    Time Frame
    2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    20 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Histologically confirmed primary CNS lymphoma. ECOG (Eastern Cooperative Oncology Group) Performance status of 0-1. Positive cerebrospinal fluid (CSF) cytology or immunohistochemical diagnosis of CSF monoclonality with or without measurable intracranial disease. Measurable (greater than 1 cm in diameter) tumor by CT scan or MRI. Progressed during first-line chemotherapy and/or radiotherapy OR relapsed after initial successful treatment. No systemic lymphoma by CT scan of the chest, abdomen, and pelvis with contrast. No leptomeningeal lymphoma by lumbar puncture for CNS cytology/flow cytometry. No ocular lymphoma by slit lamp examination. Must have adequate organ function as defined by the protocol: Adequate renal function: serum creatinine ≤ 1.5 mg/dl and/or calculated creatinine clearance ≥ 60 ml/min; Adequate hepatic function: bilirubin level ≤ 1.5 x ULN, ASAT & ALST ≤ 1.5 x ULN.Adequate bone marrow reserves: neutrophil (ANC) count ≥ 1500 /mm^3, platelet count ≥ 100,000 /mm^3, hemoglobin ≥ 9 g/dl. Age >/= 18 and </= 75 years. Signed written informed consent prior to study entry. Exclusion Criteria: Patients with human immunodeficiency virus seropositivity and systemic lymphoma manifestation. Serious uncontrolled concurrent illness. Previous brain radiotherapy, systemic chemotherapy. Concurrent chronic systemic immune therapy, targeted therapy not indicated in this study protocol. Any evidence of prior exposure to Hepatitis B virus. Unable to comprehend the study requirements or who are not likely to comply with the study parameters. Pregnant (confirmed by serum or urine β-HCG) or lactating.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Yong Wang, master
    Organizational Affiliation
    Study Director
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Citations:
    PubMed Identifier
    22179954
    Citation
    Raizer JJ, Rademaker A, Evens AM, Rice L, Schwartz M, Chandler JP, Getch CC, Tellez C, Grimm SA. Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma. Cancer. 2012 Aug 1;118(15):3743-8. doi: 10.1002/cncr.26709. Epub 2011 Dec 16.
    Results Reference
    result
    PubMed Identifier
    23828279
    Citation
    Zhang JP, Lee EQ, Nayak L, Doherty L, Kesari S, Muzikansky A, Norden AD, Chen H, Wen PY, Drappatz J. Retrospective study of pemetrexed as salvage therapy for central nervous system lymphoma. J Neurooncol. 2013 Oct;115(1):71-7. doi: 10.1007/s11060-013-1196-1. Epub 2013 Jul 5.
    Results Reference
    result
    PubMed Identifier
    24178621
    Citation
    Leshchenko VV, Kuo PY, Jiang Z, Thirukonda VK, Parekh S. Integrative genomic analysis of temozolomide resistance in diffuse large B-cell lymphoma. Clin Cancer Res. 2014 Jan 15;20(2):382-92. doi: 10.1158/1078-0432.CCR-13-0669. Epub 2013 Oct 31.
    Results Reference
    result

    Learn more about this trial

    Pemetrexed and Temozolomide in Treating Patients With Relapsed Primary Central Nervous System Lymphoma （PCNSL）

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