Lymphoma
Conditions
Keywords
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
Brief summary
RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating older patients with diffuse large B-cell lymphoma.
Detailed description
OBJECTIVES: Primary * Determine the clinical response rate in older patients with previously untreated aggressive diffuse large B-cell stage II-IV lymphoma treated with rituximab, cyclophosphamide, pegylated doxorubicin hydrochloride liposome (HCl), vincristine, and prednisone. * Determine the cardiotoxicity and myelosuppression of this regimen in these patients. Secondary * Determine disease-free survival and overall survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive rituximab intravenous (IV), cyclophosphamide IV over 1-1½ hours, pegylated doxorubicin HCl liposome IV over 1 hour, and vincristine IV on day 1, and oral prednisone on days 1-5. Patients also receive filgrastim (G-CSF) subcutaneously (SC) once daily beginning on day 6 and continuing until blood counts recover OR pegfilgrastim SC once on day 6 (24 hours after the completion of chemotherapy). Treatment repeats every 21 days for up to 8 courses in the absence of unacceptable toxicity, disease progression, active hepatitis B virus infection, or hepatitis. Patients with no response OR who achieve less than a partial response after 4 courses are removed from the study. Patients are followed at 1 month, every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter. PROJECTED ACCRUAL: A maximum of 80 patients will be accrued for this study within 27 months.
Interventions
BIOLOGICALFilgrastim
5 mcg/kg, SC daily, start 24 hours after chemotherapy
BIOLOGICALPegfilgrastim
6 mg SC one time (24 hours after chemotherapy)
BIOLOGICALRituximab
375 mg/m\^2 intravenous piggy back (IVPB) on day 1, administered 1st
DRUGCyclophosphamide
750 mg/m\^2 IVPB on day 1
DRUGPegylated liposomal doxorubicin hydrochloride
40 mg/m\^2 IV (maximum dose 90 mg) infusion over 1 hour on day 1
DRUGPrednisone
40 mg/m\^2 oral days 1 - 5.
DRUGVincristine Sulfate
2 mg IV, day 1
Sponsors
National Cancer Institute (NCI)
Ortho Biotech, Inc.
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
61 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed diffuse large B-cell lymphoma * Stage II, III, or IV disease * Previously untreated disease * Measurable or evaluable disease * No primary central nervous system (CNS) lymphoma or follicular B-cell lymphoma PATIENT CHARACTERISTICS: Age * 61 and over Performance status * Zubrod 0-2 Life expectancy * Not specified Hematopoietic * Absolute neutrophil count \> 1,000/mm\^3\* * Platelet count \> 100,000/mm\^3\* NOTE: \* Unless due to lymphoma-related hypersplenism or bone marrow infiltration Hepatic * Bilirubin \< 2 mg/dL * Hepatitis B surface antigen negative * Hepatitis B core antibody negative * Hepatitis C Virus antibody negative Renal * Creatinine \< 2 mg/dL Cardiovascular * left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram or ple gated acquisition (MUGA) scan * No uncontrolled hypertension or cardiac symptoms * Cardiologist consultation required for patients with stage A cardiac failure or any of the following known heart diseases: * Diastolic dysfunction * Prior coronary artery bypass graft * Prior percutaneous transluminal coronary angioplasty * Prior stent insertion * Prior radiotherapy to the chest * No myocardial infarction within the past 6 months * No New York Heart Association class II-IV heart failure * No uncontrolled angina * No severe uncontrolled ventricular arrhythmias * No clinically significant pericardial disease * No acute ischemic or active conduction system abnormality by electrocardiogram (EKG) Other * Not pregnant or nursing * Fertile patients must use effective contraception * No psychiatric illness that would preclude study compliance or giving informed consent * No other major life-threatening illness that would preclude study treatment PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * Not specified Radiotherapy * See Cardiovascular Surgery * See Cardiovascular
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses | Evaluation after 12 weeks (4 cycles of 21 days) | Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on International Workshop Criteria (IWG) for Tumor Response Criteria assessed with CT & FDG-PET scans at 4 cycles (12 weeks). CR defined as disappearance of all target and non-target lesions in liver & spleen, & all lymph node masses regressed to normal size. PR defined as ≥50% reduction in sum of product of diameters (SPD) for measured lymph nodes, splenic & liver lesions separately compared to baseline SPD. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow. |
| Number of Participants Experienced Grade 3 or Higher Cardiac Toxicity After Treatment: Cardiac Toxicity as Measured by Left Ventricular Ejection Fraction (LVEF) on Echocardiogram (ECHO) After 8 Courses | Up to 24 weeks (8 cycles of 21 days) | Ejection fraction ( EF) refers to the amount, or percentage, of blood that is pumped (or ejected) out of the ventricles with each contraction. Cardiology evaluation performed before second dose of pegylated liposomal doxorubicin or before entry onto trial, re-evaluation by cardiologist obtained in asymptomatic patients after chemotherapy cycle 4 and again after completion of therapy, and more often if symptomatic. Severe cardiac toxicity considered to be both Grade 3 and 4, and are graded according to NCI common toxicity criteria, CTCAE version 3.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival Rate | Up to 5 years | The percentage of participants still alive after treatment. Survival information obtained 1 month after completion of treatment, then every 3 months for 1 year, every 4 months for one year and every 6 months thereafter. |
| Disease-free Survival | Up to 5 years or until disease progression | The percentage of participants with no disease progression for period of time after treatment. Survival assessed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 3 years, and then yearly thereafter up to 5 years. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab - Combination Chemotherapy Rituximab 375 mg/m\^2 intravenous (IV), Cyclophosphamide IV over 1-1½ hours, Pegylated doxorubicin HCl liposome 40 mg/m\^2 IV over 1 hour, Vincristine 2 mg IV, day 1, & oral Prednisone 40 mg/m\^2 days 1 - 5; Filgrastim (G-CSF) 5 mcg/kg subcutaneously (SC) once daily beginning day 6 continuing until blood counts recover OR Pegfilgrastim 6 mg SC once on day 6 (24 hours after chemotherapy). Treatment repeats every 21 days for up to 8 courses. | 80 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Rituximab - Combination Chemotherapy |
|---|---|
| Age, Customized 60 to 69 | 40 participants |
| Age, Customized 70 to 79 | 27 participants |
| Age, Customized 80 to 89 | 12 participants |
| Age, Customized 90 to 99 | 1 participants |
| Region of Enrollment United States | 80 participants |
| Sex: Female, Male Female | 42 Participants |
| Sex: Female, Male Male | 38 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 80 |
| serious Total, serious adverse events | 1 / 80 |
Outcome results
Primary
Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses
Response was defined as participants with a complete response (CR), unconfirmed complete response (CRu) or partial response (PR), based on International Workshop Criteria (IWG) for Tumor Response Criteria assessed with CT & FDG-PET scans at 4 cycles (12 weeks). CR defined as disappearance of all target and non-target lesions in liver & spleen, & all lymph node masses regressed to normal size. PR defined as ≥50% reduction in sum of product of diameters (SPD) for measured lymph nodes, splenic & liver lesions separately compared to baseline SPD. CRu does not qualify for CR above, due to a residual nodal mass or an indeterminate bone marrow.
Time frame: Evaluation after 12 weeks (4 cycles of 21 days)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab - Combination Chemotherapy | Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses | Complete Response (CR) | 47 Participants |
| Rituximab - Combination Chemotherapy | Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses | Uncomfirmed Complete Response (CRu) | 8 Participants |
| Rituximab - Combination Chemotherapy | Disease Response (Complete, Complete Unconfirmed, and Partial Responses) After 4 Courses | Partial Response (PD) | 14 Participants |
Primary
Number of Participants Experienced Grade 3 or Higher Cardiac Toxicity After Treatment: Cardiac Toxicity as Measured by Left Ventricular Ejection Fraction (LVEF) on Echocardiogram (ECHO) After 8 Courses
Ejection fraction ( EF) refers to the amount, or percentage, of blood that is pumped (or ejected) out of the ventricles with each contraction. Cardiology evaluation performed before second dose of pegylated liposomal doxorubicin or before entry onto trial, re-evaluation by cardiologist obtained in asymptomatic patients after chemotherapy cycle 4 and again after completion of therapy, and more often if symptomatic. Severe cardiac toxicity considered to be both Grade 3 and 4, and are graded according to NCI common toxicity criteria, CTCAE version 3.0.
Time frame: Up to 24 weeks (8 cycles of 21 days)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab - Combination Chemotherapy | Number of Participants Experienced Grade 3 or Higher Cardiac Toxicity After Treatment: Cardiac Toxicity as Measured by Left Ventricular Ejection Fraction (LVEF) on Echocardiogram (ECHO) After 8 Courses | 10 participants |
Secondary
Disease-free Survival
The percentage of participants with no disease progression for period of time after treatment. Survival assessed every 3 months for 1 year, every 4 months for 2 years, every 6 months for 3 years, and then yearly thereafter up to 5 years.
Time frame: Up to 5 years or until disease progression
Secondary
Survival Rate
The percentage of participants still alive after treatment. Survival information obtained 1 month after completion of treatment, then every 3 months for 1 year, every 4 months for one year and every 6 months thereafter.
Time frame: Up to 5 years