Idarubicin Based Combined Modality Therapy in Primary CNS Lymphoma

Study Overview
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Brief Summary
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Idarubicin combined with high dose methotrexate and moderate dose radiotherapy will achieve similar survival outcomes but with reduced neurotoxicity compared to regimens using methotrexate with high dose radiotherapy.

Detailed Description
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Combined modality therapy in PCNSL has improved survival outcomes but at the cost of unacceptable rates of neurotoxicity when high dose radiotherapy is used. Idarubicin has activity in systemic lymphomas and crosses the blood brain barrier and may add to the efficacy of methotrexate. By combining these 2 drugs with moderate dose radiotherapy survival outcomes should be optimal but with lower rates of neurotoxicity. Comparison: TROG has previously performed a phase 2 study using methotrexate with high dose radiotherapy and this will allow comparison of survival and neurotoxicity rates.

Official Title
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A Phase 2 Study of Idarubicin Based Combined Modality Therapy in Primary Central Nervous System Lymphoma

Conditions
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Primary Central Nervous System Lymphoma

Intervention / Treatment
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* Drug: Idarubicin, Methotrexate, Filgrastim, intrathecal Ara-C
* Radiation: Radiation Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically proven primary CNS lymphoma. Absence of disease outside the CNS. ECOG performance status 0-3 Negative HIV status. Peripheral blood counts with granulocytes >1.5 x 109L and platelets > 100 x 109L. Serum creatinine <150mmol/L. Serum bilirubin <1.5 times and AST <2 times upper limit of normal. Age >18 and <=70 years. Patients must give written informed consent. Corticosteroids prior to histological diagnosis are allowed. Exclusion Criteria: Previous history of malignancy (other than non-melanomatous skin carcinoma, or carcinoma in situ of cervix completely excised). Patients who are pregnant or lactating. NYHA (New York State Heart Association classification) cardiac failure grade 3 Macroscopic spinal thecal or spinal cord disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Idarubicin, Methotrexate, Filgrastim, intrathecal Ara-C<br>* Idarubicin 15mg/m2 days 1, 22. Filgrastim 5mcg/kg until neutrophil recovery days 2, 23. Methotrexate 1g/m2 days 15, 36 and 50.<br>Radiation: Radiation Therapy<br>* Whole brain Irradiation, 30Gy in 20 fractions over 4 weeks<br>* Other names: Radiation, Radiotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To estimate the median and 2 year overall survival. |  | Estimate of survival at 2 years and at 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess acute toxicity. |  | Interim actute toxicity analyses will be performed at accrual points: 5, 10, 15, 20 and 25 patients. | 
| Assess functional indices of living in patients with PCNSL. |  | Analysis will be at 5 years. | 
| To estimate the risk of late neurotoxicity relative to results achieved in TROG 92.01. |  | Analysis at 3 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphoma, PCNSL, Primary CNS lymphoma