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

Phase 2

• Conditions: Central Nervous System Tumors
• Interventions: Drug: Pemetrexe; Drug: Temozolomide

• Registration Number: NCT01985451
• Lead Sponsor: Rongjie Tao

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.

Basic Information
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Recruitment & Eligibility
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Study & Design

Study Timeline

• Study Start: 2013-03
• Status Verified: 2013-11
• Study First Submitted: 2013-11-04
• Study First Submitted QC: 2013-11-08
• Last Update Submitted: 2013-11-08
• Study First Posted: 2013-11-15
• Last Update Posted: 2013-11-15
• Primary Completion: 2015-03
• Study Completion: 2015-03

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 15

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
complete response (CR)	2 years	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

Name	Time	Method
Failure-free survival (PFS)	2 years	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	2 years	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)	2 years	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.