Lymphoma
Conditions
Keywords
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, anaplastic large cell lymphoma
Brief summary
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
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.
Interventions
DRUGcisplatin
DRUGetoposide
DRUGgemcitabine
DRUGmethylprednisolone
Sponsors
National Cancer Institute (NCI)
SWOG Cancer Research Network
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 2-year Overall Survival Rate | 0-2 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 2-year Progression-free Survival Rate | 0-2 years | 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. |
| Response Rate | up to 3 years or time of disease progression | 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. |
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | up to 18 weeks of protocol treatment | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PEGS Patients received IV cisplatin 25 mg/m2 days 1-4, etoposide 40 mg/m2 days 1-4, gemcitabine 1000 mg/m2 day 1 and solumedrol 250 mg days 1-4 of a 21 day cycle for 6 cycles. | 33 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Death | 2 |
| Overall Study | not eligible | 1 |
| Overall Study | not protocol specified | 2 |
| Overall Study | Progression | 6 |
Baseline characteristics
| Characteristic | PEGS |
|---|---|
| Age, Continuous | 60 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 31 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 33 / 33 |
| serious Total, serious adverse events | 5 / 33 |
Outcome results
Primary
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.
Time frame: 0-2 years
Population: All eligible patients who started protocol treatment were included in the analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEGS | 2-year Overall Survival Rate | 31 percentage of participants |
Secondary
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.
Time frame: 0-2 years
Population: All eligible patients who started protocol treatment were included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PEGS | 2-year Progression-free Survival Rate | 12 percentage of participants |
Secondary
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.
Time frame: up to 18 weeks of protocol treatment
Population: Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 3.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Anorexia | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Tinnitus | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Albumin, serum-low (hypoalbuminemia) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Allergic reaction/hypersensitivity | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Ataxia (incoordination) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Auditory/Ear-Other (Specify) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Blood/Bone Marrow-Other (Specify) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Colitis, infectious (e.g., Clostridium difficile) | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Creatinine | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Diarrhea | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Dysphagia (difficulty swallowing) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Dyspnea (shortness of breath) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Fatigue (asthenia, lethargy, malaise) | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Febrile neutropenia | 4 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Gastrointestinal-Other (Specify) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Glucose, serum-high (hyperglycemia) | 4 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Glucose, serum-low (hypoglycemia) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Hemoglobin | 9 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Hemorrhage, CNS | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Hypotension | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Incontinence, anal | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Blood | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Inf (clin/microbio) w/Gr 3-4 neuts - Colon | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Inf w/normal ANC or Gr 1-2 neutrophils - Bladder | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Inf w/normal ANC or Gr 1-2 neutrophils - Lung | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Leukocytes (total WBC) | 8 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Lymphopenia | 7 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Magnesium, serum-low (hypomagnesemia) | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Nausea | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neurology-Other (Specify) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neuropathy: motor | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neuropathy: sensory | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Neutrophils/granulocytes (ANC/AGC) | 16 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Pain - Abdomen NOS | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Platelets | 8 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Potassium, serum-low (hypokalemia) | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Renal failure | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Sodium, serum-low (hyponatremia) | 2 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Thrombotic microangiopathy | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Tumor lysis syndrome | 1 Participants |
| PEGS | Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Uric acid, serum-high (hyperuricemia) | 1 Participants |
Secondary
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.
Time frame: up to 3 years or time of disease progression
Population: All eligible patients who started protocol treatment were included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PEGS | Response Rate | Complete Response | 6 participants |
| PEGS | Response Rate | Unconfirmed Complete Response | 2 participants |
| PEGS | Response Rate | Partial Response | 5 participants |
| PEGS | Response Rate | No Response | 20 participants |