Clinical trial NCT01985451: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Central Nervous System Tumors
Keywords: Lymphoma
Lead sponsor: Shandong Cancer Hospital and Institute
Sponsor class: OTHER
Collaborators: name: National Natural Science Foundation of China
First posted: 2013-11-15
Enrollment: 15
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: complete response (CR)
timeFrame: 2 years
Secondary outcomes:
measure: Failure-free survival (PFS)
timeFrame: 2 years
measure: Toxicity
timeFrame: 2 years
measure: Overall response rate (ORR)
timeFrame: 2 years
Other outcomes:
Locations:
Study officials:
affiliation: Study Director
name: Yong Wang, master
role: STUDY_DIRECTOR
References:
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.
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.
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.