Etoposide, Methylprednisolone, High-dose Cytarabine and Oxaliplatin as 2nd Line Therapy for Non-Hodgkin's Lymphoma (NHL)

Study Overview
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Brief Summary
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Oxaliplatin will be used instead of cisplatin in well-known salvage regimen of etoposide, methylprednisolone, cytarabine and cisplatin (ESHAP). Clinical efficacy and toxicity of this ESHAOX salvage regimen will be evaluated in refractory or relapsed non-Hodgkin's lymphoma patients.

Detailed Description
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Patients with aggressive non-Hodgkin's lymphoma (NHL) are known to have a malignancy considered curable in many cases. However, diagnosis of refractory or relapsed disease is devastating and the treatment is difficult because regimens of chemotherapy used as salvage therapy are available only in limited numbers. ESHAP, consisting of etoposide, methylprednisolone, high-dose cytarabine and cisplatin, is one of commonly used salvage regimen, and showed its efficacy and feasibility. But it often requires discontinuation of the treatment due to its myelosuppression, neuropathy and renal toxicity, which can also impede further treatment. Oxaliplatin, a platinum coordination complex with an oxalato-ligand as the leaving group and a 1,2-diaminocyclohexane carrier, possesses higher cytotoxic potency on molar basis than cisplatin and carboplatin, and was reported to be active in patients with NHL as a single agent. In addition, the substitution of cisplatin by oxaliplatin in the DHAP regimen, another commonly used one in relapsed or refractory NHL, showed meaningful anti-tumor activity with favorable toxicity profile. Based on preclinical and clinical findings, we will conduct a multi-center phase II study of ESHAOX, which substitutes oxaliplatin with cisplatin in the ESHAP regimen, to evaluate the efficacy and toxicity profile in patients with recurrent or refractory NHL.

Official Title
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Phase II Study of Etoposide, Methylprednisolone, High-dose Cytarabine and Oxaliplatin (ESHAOX) for Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma

Conditions
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Non-Hodgkin's Lymphoma

Intervention / Treatment
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* Drug: Oxaliplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously histologically confirmed aggressive lymphomas, defined according to WHO classification (except Burkitt's lymphoma, lymphoblastic lymphoma) Failure to achieve a complete remission with the initial induction chemotherapy, or recurrent disease Performance status (ECOG) ≤3 Age ≤ 75 Treated with at least one CHOP or CHOP-derived doxorubicin containing regimen At least one or more uni-dimensionally measurable lesion(s) defined as; ≥2 cm by conventional CT or ≥ 1 cm by spiral CT or skin lesion (photographs should be taken) or measurable lesion by physical examination Adequate organ functions defined as; ANC > 1,500/ul, platelet > 75,000/ul, transaminases < 3 X upper normal values; bilirubin < 2 mg% Written informed consent approved by Institutional Review Board Exclusion Criteria: Any other malignancies within the past 5 years except skin basal cell ca or CIS of cervix Serious co-morbid diseases Pregnancy or breast-feeding

Ages Eligible for Study
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Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxaliplatin, response<br>relapsed or refractory non-Hodgkin's lymphoma | Drug: Oxaliplatin<br>* Oxaliplatin, 130 mg per square meter, on day 1<br>* Other names: cytarabine, 2 g per square meter on day 5;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | The Overall Response Rate was measured by the number of patients per the total treatment population who partially or completely responded to treatment. Response was evaluated according to the International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas. | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Worst Toxicity Grade by Patient | graded by National Cancer Institute Common Toxicity Criteria of Adverse Event version 3.0 | up to 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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oxaliplatin, ESHAOX, refractory, relapsed, non-hodgkin's lymphoma