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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: etoposide; Drug: methylprednisolone; Drug: cisplatin; Drug: gemcitabine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tucson, Arizona, United States, 85724-5024
      • Arizona Cancer Center at University of Arizona Health Sciences Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Fremont, California, United States, 94538
      • Kaiser Permanente - Fremont
    • Hayward, California, United States, 94545
      • Kaiser Permanente Medical Center - Hayward
    • Oakland, California, United States, 94611
      • Kaiser Permanente Medical Center - Oakland
    • Sacramento, California, United States, 95823
      • South Sacramento Kaiser-Permanente Medical Center
    • San Francisco, California, United States, 94115
      • Kaiser Permanente Medical Center - San Francisco Geary Campus
    • San Jose, California, United States, 95119
      • Kaiser Permanente Medical Center - Santa Teresa
    • San Rafael, California, United States, 94903
      • Kaiser Foundation Hospital - San Rafael
    • Santa Clara, California, United States, 95051
      • Kaiser Permanente Medical Center - Santa Clara Kiely Campus
    • Santa Rosa, California, United States, 95403
      • Kaiser Permanente Medical Center - Santa Rosa
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Medical Center - South San Francisco
    • Stockton, California, United States, 95210
      • Kaiser Permanente Medical Facility - Stockton
    • Vallejo, California, United States, 94589
      • Kaiser Permanente Medical Center - Vallejo
    • Walnut Creek, California, United States, 94596
      • Kaiser Permanente Medical Center - Walnut Creek
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
  • Florida
    • Orlando, Florida, United States, 32806
      • M.D. Anderson Cancer Center at Orlando
  • Illinois
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital Cancer Care Institute
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Springfield, Illinois, United States, 62781-0001
      • Regional Cancer Center at Memorial Medical Center
  • Kansas
    • Salina, Kansas, United States, 67401
      • Tammy Walker Cancer Center at Salina Regional Health Center
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0093
      • Lucille P. Markey Cancer Center at University of Kentucky
  • Louisiana
    • Monroe, Louisiana, United States, 71210
      • Louisiana State University Health Sciences Center - Monroe
    • Shreveport, Louisiana, United States, 71105
      • Highland Clinic
    • Shreveport, Louisiana, United States, 71130-3932
      • Feist-Weiller Cancer Center at Louisiana State University Health Sciences
  • Michigan
    • Ann Arbor, Michigan, United States, 48106-0995
      • Saint Joseph Mercy Cancer Center
    • Ann Arbor, Michigan, United States, 48106
      • CCOP - Michigan Cancer Research Consortium
    • Dearborn, Michigan, United States, 48123-2500
      • Oakwood Cancer Center at Oakwood Hospital and Medical Center
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Flint, Michigan, United States, 48503
      • Genesys Hurley Cancer Institute
    • Grosse Pointe Woods, Michigan, United States, 48236
      • Van Elslander Cancer Center at St. John Hospital and Medical Center
    • Jackson, Michigan, United States, 49201
      • Foote Memorial Hospital
    • Lansing, Michigan, United States, 48912-1811
      • Sparrow Regional Cancer Center
    • Livonia, Michigan, United States, 48154
      • St. Mary Mercy Hospital
    • Pontiac, Michigan, United States, 48341-2985
      • St. Joseph Mercy Oakland
    • Port Huron, Michigan, United States, 48060
      • Mercy Regional Cancer Center at Mercy Hospital
    • Saginaw, Michigan, United States, 48601
      • Seton Cancer Institute at Saint Mary's - Saginaw
    • Warren, Michigan, United States, 48093
      • St. John Macomb Hospital
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Cancer Center
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • New York
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14623
      • Interlakes Oncology/Hematology PC
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
  • Washington
    • Bellingham, Washington, United States, 98225
      • St. Joseph Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Kennewick, Washington, United States, 99336
      • Columbia Basin Hematology
    • Mt. Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Cancer Care Center
    • Poulsbo, Washington, United States, 98370
      • Harrison Poulsbo Hematology and Onocology
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Minor and James Medical, PLLC
    • Seattle, Washington, United States, 98112
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98122-4307
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Seattle, Washington, United States, 98122
      • Polyclinic First Hill
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Spokane, Washington, United States, 99218
      • Evergreen Hematology and Oncology, PS
    • Wenatchee, Washington, United States, 98801-2028
      • Wenatchee Valley Medical Center
  • Wyoming
    • Casper, Wyoming, United States, 82609
      • Rocky Mountain Oncology
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEGS Treatment; 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: etoposide; Drug: methylprednisolone; Drug: cisplatin; Drug: gemcitabine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Daruka Mahadevan, MD, PhD, University of Arizona

Publications and helpful links

General Publications

• Mahadevan D, Unger JM, Spier CM, Persky DO, Young F, LeBlanc M, Fisher RI, Miller TP. Phase 2 trial of combined cisplatin, etoposide, gemcitabine, and methylprednisolone (PEGS) in peripheral T-cell non-Hodgkin lymphoma: Southwest Oncology Group Study S0350. Cancer. 2013 Jan 15;119(2):371-9. doi: 10.1002/cncr.27733. Epub 2012 Jul 25.

Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: May 3, 2005
• First Submitted That Met QC Criteria: May 3, 2005
• First Posted (Estimate): May 4, 2005

Study Record Updates

• Last Update Posted (Estimate): October 1, 2014
• Last Update Submitted That Met QC Criteria: September 18, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage IV adult diffuse mixed cell lymphoma; anaplastic large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse mixed cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult diffuse mixed cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Antiviral Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Gemcitabine; Methylprednisolone; Etoposide
• Other Study ID Numbers: CDR0000425643; U10CA032102 (U.S. NIH Grant/Contract); S0350 (Other Identifier: SWOG)