S0350 Combination Chemotherapy in Treating Patients With Newly Diagnosed Stage II, Stage III, or Stage IV Peripheral T-Cell Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cisplatin, etoposide, gemcitabine, and methylprednisolone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase II trial is studying how well combination chemotherapy works in treating patients with newly diagnosed stage II, stage III, or stage IV T-cell non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine 2-year overall survival of patients with newly diagnosed, bulky stage II or stage III or IV peripheral T-cell non-Hodgkin's lymphoma treated with cisplatin, etoposide, gemcitabine, and methylprednisolone. Secondary Determine the toxicity of this regimen in these patients. Determine the response rate (complete unconfirmed response, complete response, and partial response) in patients treated with this regimen. Determine progression-free survival of patients treated with this regimen. OUTLINE: This is a pilot, multicenter study. Patients receive cisplatin IV over 30-60 minutes, etoposide IV over 30-60 minutes, and methylprednisolone IV over 5 minutes on days 1-4. Patients also receive gemcitabine IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed at 3-6 weeks, 3 months, and then every 6 months for up to 3 years. PROJECTED ACCRUAL: A total of 55 patients will be accrued for this study within 3 years.

Official Title
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Phase II Trial of Cisplatin Plus Etoposide Plus Gemcitabine Plus Solumedrol (PEGS) in Peripheral T-Cell Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: cisplatin
* Drug: etoposide
* Drug: gemcitabine
* Drug: methylprednisolone


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of peripheral T-cell non-Hodgkin's lymphoma Newly diagnosed, relapsed or progressing disease after 1 prior treatment with a non-platinum based chemotherapy (e.g., CHOP) Bulky stage II or stage III or IV disease The following histologies are not eligible: T-cell prolymphocytic leukemia T-cell large granular lymphocytic leukemia Any NK-cell leukemia Adult T-cell leukemia/lymphoma Mycosis fungoides/Sézary syndrome Lymphomatoid papulosis Nasal-type extranodal NK/T-cell lymphoma Enteropathy-type T-cell lymphoma Hepatosplenic T-cell lymphoma Subcutaneous panniculitis-like T-cell lymphoma Angioimmunoblastic T-cell lymphoma Primary cutaneous anaplastic large cell lymphoma (ALCL) ALCL with CD30, ALK, and EMA expression ALCL morphology that fails to express ALK or EMA allowed provided T-cell lineage is confirmed by immunotyping or genetic testing Bidimensionally measurable disease Adequate samples (e.g., core biopsies, especially multiple core biopsies) from the original diagnostic specimen available Needle aspiration or cytology is not considered adequate samples No clinical evidence of Central nervous system (CNS) involvement by lymphoma PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic Bilirubin ≤ 2 times upper limit of normal Renal Creatinine clearance ≥ 30 mL/min Cardiovascular No history of congestive heart failure No history of myocardial infarction No history of unstable angina No history of asymptomatic arrhythmias Ejection fraction normal by multigated acquisition (MUGA) scan (for patients with questionable cardiac history) No other history of impaired cardiac status Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No known HIV positivity Mild clinical hearing loss allowed provided patient is willing to accept the potential for worsening of hearing loss No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix Must have had a chest x-ray or CT scan of the chest and a CT scan of the abdomen and pelvis within the past 28 days PRIOR CONCURRENT THERAPY: Biologic therapy At least 3 weeks since prior biologic therapy No concurrent routine use of bone marrow colony-stimulating factors Chemotherapy No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy No prior radiotherapy for this cancer No concurrent radiotherapy Surgery Not specified Other No prior cytotoxic therapy for this cancer Concurrent enrollment in SWOG-8819 or SWOG-8947 allowed

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: PEGS Treatment<br>VP-16 (Etoposide) 40 mg/m2 IV Days 1-4 Methyl Prednisolone 250 mg IV Days 1-4 Cisplatin 25 mg/m2 IV Days 1-4 Gemcitabine 1,000 mg/m2 IV Day 1 | Drug: cisplatin<br> <br> Drug: etoposide<br> <br> Drug: gemcitabine<br> <br> Drug: methylprednisolone<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Overall Survival Rate | The overall survival rate is the percentage of patients who are alive 2 years after registration to the study. Overall survival is defined as the time between study registration and death due to any cause. | 0-2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Progression-free Survival Rate | Progression-free survival rate is the percentage of patients who do not show signs of progression at 2 years after registration to the study, including those whose disease has either completely or partially responded to treatment, or those whose disease is stable. Progression-free survival is defined as the time between study registration and documented progression, or death if no progression was observed. | 0-2 years | 
| Response Rate | Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. | up to 3 years or time of disease progression | 
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. | up to 18 weeks of protocol treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anaplastic large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage IV adult diffuse mixed cell lymphoma, contiguous stage II adult diffuse mixed cell lymphoma, noncontiguous stage II adult diffuse mixed cell lymphoma, contiguous stage II adult diffuse large cell lymphoma, noncontiguous stage II adult diffuse large cell lymphoma, stage III adult diffuse large cell lymphoma, stage IV adult diffuse large cell lymphoma