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

Central Nervous System Tumors Clinical Trial

Official title:

Phase II Trial of Pemetrexed and Temozolomide in Treating Patients With Relapsed PCNSL

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01985451
• Other study ID #: ShandongCHI002
• Secondary ID: ShandongCHI
• Status: Active, not recruiting
• Phase: Phase 2
• First received: November 4, 2013
• Last updated: November 8, 2013
• Start date: March 2013
• Est. completion date: March 2015

Study information

• Verified date: November 2013
• Source: Shandong Cancer Hospital and Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 75 Years

Eligibility

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 ß-HCG) or lactating.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Central Nervous System Neoplasms
• Central Nervous System Tumors
• Nervous System Neoplasms

Intervention

Drug:
• Pemetrexe
Patients with relapsed PCNSL patients were treated with high-dose pemetrexed (900mg/m²).
• Temozolomide
Patients with relapsed PCNSL patients were treated with temozolomide (200mg/m² day 1-5,28).

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Rongjie Tao	National Natural Science Foundation of China

References & Publications (3)

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. — View 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 2 — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 years	No
Secondary	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.	2 years	No
Secondary	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.	2 years	No
Secondary	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.	2 years	No