Lymphomatoid Granulomatosis, Granulomatosis, Lymphomatoid, Non-Hodgkins Lymphoma, Lymphoproliferative Disorder
Conditions
Keywords
Epstein-Barr Virus, Lymphoproliferative Disorder, Viral, Immunosuppression, Lymphoma
Brief summary
This study will evaluate the response and long-term effects of alpha-interferon in patients with lymphomatoid granulomatosis (LYG). The disease causes proliferation of destructive cells involving the lungs, skin, kidneys, and central nervous system. Patients ages 12 and older who have LYG and who are not pregnant, or breast feeding may be eligible for this study. Alpha interferon or chemotherapy, or both, will be used. Alpha interferon is a protein the body naturally produces. If patients have grade 3 disease, they will usually receive etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH)-rituximab (EPOCH-R) chemotherapy (each letter representing a drug). If patients have grade 1 or 2 disease, they will usually receive alpha interferon. If patients have LYG after receiving alpha interferon and/or EPOCH-R, they may receive rituximab alone or with alpha interferon. Rituximab is an antibody, binding to a specific molecule cluster of differentiation 20 (CD20) present on most B-cell lymphomas. Doses of several drugs in EPOCH-R may be increased if patients tolerated them in the previous cycle. If patients respond to EPOCH-R but still have low grade LYG, they may receive alpha interferon. Researchers will also try to obtain a biopsy of patient's lesions, to help in understanding the disease. Patients self-administer alpha interferon by injection under the skin three times weekly. They will visit the clinic every 2 to 12 weeks for follow-up. Patients will receive alpha interferon for 1 year after LYG goes away, depending on response. EPOCH-R has these drugs: rituximab by vein on Day 1; prednisone by mouth on Days 1 to 5; etoposide, doxorubicin, and vincristine as a continuous intravenous infusion on Days 1 to 5; and cyclophosphamide by intravenous injection over 1 hour on Day 5. Each cycle lasts 3 weeks: 5 days of chemotherapy and 16 days of no chemotherapy. Etoposide, doxorubicin, and vincristine are infused through a small pump worn by patients. The drugs are given over 5 days through a central intravenous catheter. There are two cycles of EPOCH-R beyond a maximum response, with six cycles maximum. To reduce harm to bone marrow, patients receive granulocyte colony stimulating factor (G-CSF), self-administered by injection under the skin daily for approximately 10 days between chemotherapy cycles. If at the end of therapy, patients have a complete response, treatment will stop. If there is residual low-grade disease, patients may receive alpha interferon. Alpha interferon can have flu-like side effects of headache, fever, chills, and body aches. EPOCH-R drugs can cause gastrointestinal problems, hair loss, and weakness. Granulocyte colony-stimulating factor (G-CSF) can cause bone pain, body aches, and hair thinning. Chemotherapy can cause some patients to develop leukemia. This study may or may not have a direct benefit for participants. It is not certain whether the new therapy will help decrease tumors. However, knowledge gained may improve the understanding of and treatment for LYG. ...
Detailed description
BACKGROUND: * Lymphomatoid granulomatosis (LYG) is an angiocentric destructive proliferation of lymphoid cells predominantly involving the lungs, skin, kidneys, and central nervous system. * It is divided into three grades, depending on the degree of necrosis and cellular atypia. The grades of disease are histologically based and do not necessarily correlate with clinical outcome. However, like other Epstein-Barr virus (EBV) related lymphoproliferative disorders (LPD's), LYG can transform into an aggressive large B-cell lymphoma, which would be included within the grade 3 category. It is important to note that not all grade 3 lesions are a large B-cell lymphoma. * Current evidence shows that LYG is a disease of B cells. OBJECTIVES: * To determine the response and long-term efficacy of alpha-Interferon in patients with lymphomatoid granulomatosis (LYG). * To determine the response and long-term efficacy of dose-adjusted (DA)-etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin rituximab (EPOCH-R) chemotherapy in patients with grade 3 LYG or in patients who have failed interferon. ELIGIBILITY: * Patients must have a tissue diagnosis of grade 1, 2 and/or 3 LYG (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI). * Patients with any stage of disease will be eligible. * Previously untreated and treated patients are eligible. * Patients aged 12 or older will be eligible. DESIGN: * Interferon is used as initial treatment in patients with grades 1 and 2 LYG. Patients will receive interferon for one year past complete remission (CR). * Patients who progress after or during interferon, and patients with grade 3 LYG will receive aggressive combination chemotherapy with DA-EPOCH-R (rituximab, etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone). * Patients who fail one treatment approach may be crossed over to the other. * A total of 105 patients will be enrolled at this single institution.
Interventions
BIOLOGICALInterferon
For lymphomatoid granulomatosis (LYG) Grade 1 and 2: Interferon starting at 7.5 million Units subcutaneous (subQ) 3 times a week and increasing on the following schedule: 10 million U; 15 million U; 20 million U; 25 million U; and increased in 5 million U increments, as tolerated. Patients continue taking interferon for 1 year beyond complete remission (CR).
DRUGRituxan and EPOCH
For lymphomatoid granulomatosis (LYG) Grade 3: EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) every 3 weeks for 6 cycles.
PROCEDURETumor biopsy
Baseline (optional).
PROCEDUREBone marrow biopsy
Baseline.
BIOLOGICALBone marrow aspirate
Baseline.
PROCEDURELumber puncture
Baseline.
DIAGNOSTIC_TESTCT
Arm 1: At baseline, then every 4 weeks until on stable dose of interferon or a maximum of 6 monthly scans, then every 3 months while receiving interferon, and following completion of interferon. In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years. Arm 2: At baseline, following cycle 4, and following cycle 6 of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years.
DIAGNOSTIC_TESTBrain MRI
Arm 1: At baseline, then every 4 weeks until on stable dose of interferon or a maximum of 6 monthly scans, then every 3 months while receiving interferon, and following completion of interferon. In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years (patients with central nervous system (CNS) disease only). Arm 2: At baseline, following cycle 4, and following cycle 6 of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R). In surveillance, every 3 months for 1 year, every 4 months for 1 year, every 6 months for 1 year and yearly thereafter for 2 years (patients with CNS disease only).
DIAGNOSTIC_TESTEchocardiogram
For participants receiving \> 450 mg/m\^2 doxorubicin.
DIAGNOSTIC_TESTFDG-PET
Arm 1: Baseline and following completion of interferon. Arm 2: Baseline and following completion of etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R).
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* INCLUSION CRITERIA: Patients must have a tissue-diagnosis of grade 1, 2 and/or 3 lymphomatoid granulomatosis (LYG) (or a diagnosis consistent with LYG) confirmed by the Laboratory of Pathology, National Cancer Institute (NCI). Final histopathologic classification and pathologic grade will be determined by Stephania Pittaluga, medical doctor (M.D.) or her designee. Patients with any stage of disease will be eligible. Previously untreated and treated patients are eligible. Patients aged 12 or older will be eligible.
Exclusion criteria
Patients with a history of coronary artery disease with angina pectoris, or a history of congestive heart failure will not be eligible to receive. etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) chemotherapy. Patients with significant renal (serum creatinine (Cr.) greater than 1.5 mg/dl or creatinine clearance less than 40 cc/min) or hepatic (bilirubin greater than 2.5 x upper limit of normal (ULN) dysfunction not due to tumor involvement will not be eligible to receive DA-EPOCH-R chemotherapy. Informed consent must be obtained. Patients who in the opinion of the principal investigator are poor psychiatric or medical risk are not eligible. Patients who received \> 450 mg/m\^2 doxorubicin and have a cardiac ejection fraction on echocardiogram less than or equal to 40% on protocol entry are not eligible to received DA-EPOCH-R. Patients with prior hepatitis B exposure may be included in the study provided that they have hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels below the World Health Organizations cutoff of 100 IU/mL prior to starting therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From study enrollment and throughout treatment, up to a maximum of 40 months for the 2 interferon groups and 8 months for the 2 EPOCH-R groups. | Overall response rate will be classified as the following: complete remission (CR), partial remission (PR), disease progression or disease stabilization measured by the Response Criteria. CR is no evidence of active disease on restaging for at least 2 months duration. All lesions must have decreased by \> 75%, be gallium or positron emission tomography (PET) negative (if obtained) and be stable for \> 3 months without new lesions appearing. PR is 50% or greater decrease in the sum of the products of the diameters of all measurable lesions for at least one month. Disease progression is 25% or greater progression in the sum of the products of the diameter of any measurable lesion over one month or the appearance or any new lesion consistent with metastatic disease. Disease stabilization is no change in the sum of the products of the diameters of all measurable lesions over two months and no new lesions consistent with disease. |
| Progression Free Survival (PFS) | Assessed from date of study enrollment until time of disease relapse, disease progression, death, or last follow-up, whichever comes first, up to a maximum of 27 years for the 2 interferon groups and 20 years for the 2 EPOCH-R groups. | PFS is defined as the duration of time from the date of study enrollment until the date of disease relapse, disease progression, death, or last follow-up, whichever occurs first, using the Kaplan-Meier method. Response was assessed by the Lugano Classification Response Criteria for Non-Hodgkin lymphoma (NHL). Disease progression is defined as an increase of ≥ 50% from the product of the perpendicular diameter (PPD) nadir and an increase in longest transverse diameter of a lesion (LDi) or shortest axis perpendicular diameter (SDi) from nadir of \>0.5 cm for lesions \<2 cm or \>1.0 cm for lesions \>2 cm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Assessed from date of study enrollment until time of death or last follow-up, whichever comes first, up to a maximum of 27 years. | OS is defined as the time from treatment start date until date of death or date last known alive. The median OS will be determined and reported along with a 95% confidence interval. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | Adverse Events were monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, up to a maximum of 49 months. | Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Toxicity Criteria (CTC v2.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Participants Treated With Initial Interferon Therapy Interferon starting at 7.5 million Units subcutaneous (subQ) 3 times a week and increasing on the designated schedule, as tolerated. Participants continue taking interferon for 1 year beyond complete remission (CR). Patients who progress may crossover to receive etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R).
Interferon: For lymphomatoid granulomatosis (LYG) Grade 1 and 2: Interferon starting at 7.5 million Units subcutaneous (subQ) 3 times a week and increasing on the following schedule: 10 million U; 15 million U; 20 million U; 25 million U; and increased in 5 million U increments, as tolerated. Participants continue taking interferon for 1 year beyond complete remission (CR). | 60 |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) every 3 weeks for up to 6 cycles, based on response.
Rituxan and EPOCH: For lymphomatoid granulomatosis (LYG) Grade 3: EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, rituximab) every 3 weeks for 6 cycles.
Participants who relapse or progress may crossover to receive interferon. | 28 |
| Participants Enrolled But Not Treated Participants were enrolled and not treated with initial interferon or etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (EPOCH-R) therapy. | 5 |
| Participant Treated With Rituximab and Radiation Only Participant treated with rituximab and radiation only. Did not receive either interferon or etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (EPOCH-R) therapy. | 1 |
| Total | 94 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Cross-Over After Initial Treatment | Complicating disease/intercurrent illness | 1 | 1 | 0 | 0 |
| Cross-Over After Initial Treatment | Disease progression | 4 | 2 | 0 | 0 |
| Cross-Over After Initial Treatment | Received alternative treatment | 4 | 0 | 0 | 0 |
| Cross-Over After Initial Treatment | Refused further treatment | 1 | 0 | 0 | 0 |
| Initial Treatment | Complicating disease/intercurrent illness | 6 | 1 | 0 | 0 |
| Initial Treatment | Did not receive protocol treatment | 0 | 0 | 5 | 0 |
| Initial Treatment | Disease progression | 21 | 3 | 0 | 0 |
| Initial Treatment | Received alternative treatment | 2 | 1 | 0 | 0 |
| Initial Treatment | Received treatment with whole brain radiation therapy (WBRT) + Rituximab | 0 | 0 | 0 | 1 |
| Initial Treatment | Refused further treatment | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Participants Enrolled But Not Treated | Participant Treated With Rituximab and Radiation Only | Total | Participants Treated With Initial Interferon Therapy |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 5 Participants | 1 Participants | 87 Participants | 54 Participants |
| Age, Continuous | 47.42 years STANDARD_DEVIATION 12.76 | 42.64 years STANDARD_DEVIATION 12.47 | 18 years STANDARD_DEVIATION 0 | 46.33 years STANDARD_DEVIATION 13.64 | 46.6 years STANDARD_DEVIATION 13.88 |
| Baseline Histologic Grade of Lymphomatoid Granulomatosis (LYG) Grade 1 | 1 Participants | 0 Participants | 0 Participants | 23 Participants | 22 Participants |
| Baseline Histologic Grade of Lymphomatoid Granulomatosis (LYG) Grade 2 | 2 Participants | 1 Participants | 0 Participants | 22 Participants | 19 Participants |
| Baseline Histologic Grade of Lymphomatoid Granulomatosis (LYG) Grade 3 | 22 Participants | 2 Participants | 0 Participants | 37 Participants | 13 Participants |
| Baseline Histologic Grade of Lymphomatoid Granulomatosis (LYG) NA | 3 Participants | 2 Participants | 1 Participants | 12 Participants | 6 Participants |
| Disease Sites Central nervous system (CNS) | 8 Participants | 0 Participants | 1 Participants | 30 Participants | 21 Participants |
| Disease Sites Kidney | 4 Participants | 0 Participants | 0 Participants | 15 Participants | 11 Participants |
| Disease Sites Liver | 6 Participants | 1 Participants | 0 Participants | 17 Participants | 10 Participants |
| Disease Sites Lung | 28 Participants | 5 Participants | 0 Participants | 93 Participants | 60 Participants |
| Disease Sites Lymph node | 1 Participants | 0 Participants | 0 Participants | 5 Participants | 4 Participants |
| Disease Sites Other | 9 Participants | 2 Participants | 0 Participants | 20 Participants | 9 Participants |
| Disease Sites Skin | 11 Participants | 1 Participants | 0 Participants | 32 Participants | 20 Participants |
| Disease Sites Spleen | 3 Participants | 1 Participants | 0 Participants | 10 Participants | 6 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 | 24 Participants | 5 Participants | 1 Participants | 77 Participants | 47 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ≥2 | 4 Participants | 0 Participants | 0 Participants | 17 Participants | 13 Participants |
| Elevated lactate hydrogenase (LDH) | 12 Participants | 2 Participants | 0 Participants | 45 Participants | 31 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 28 Participants | 5 Participants | 1 Participants | 94 Participants | 60 Participants |
| Prior Therapy Chemotherapy | 4 Participants | 2 Participants | 1 Participants | 29 Participants | 22 Participants |
| Prior Therapy Corticosteroids | 14 Participants | 3 Participants | 1 Participants | 60 Participants | 42 Participants |
| Prior Therapy None | 13 Participants | 1 Participants | 0 Participants | 30 Participants | 16 Participants |
| Prior Therapy Rituximab | 3 Participants | 3 Participants | 0 Participants | 19 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 25 Participants | 5 Participants | 1 Participants | 84 Participants | 53 Participants |
| Region of Enrollment United States | 28 participants | 5 participants | 1 participants | 94 participants | 60 participants |
| Sex: Female, Male Female | 14 Participants | 2 Participants | 1 Participants | 38 Participants | 21 Participants |
| Sex: Female, Male Male | 14 Participants | 3 Participants | 0 Participants | 56 Participants | 39 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 29 / 60 | 15 / 28 | 1 / 5 | 0 / 1 | 14 / 24 | 6 / 10 |
| other Total, other adverse events | 57 / 60 | 28 / 28 | 0 / 5 | 1 / 1 | 24 / 24 | 10 / 10 |
| serious Total, serious adverse events | 21 / 60 | 20 / 28 | 0 / 5 | 0 / 1 | 15 / 24 | 6 / 10 |
Outcome results
Primary
Overall Response Rate (ORR)
Overall response rate will be classified as the following: complete remission (CR), partial remission (PR), disease progression or disease stabilization measured by the Response Criteria. CR is no evidence of active disease on restaging for at least 2 months duration. All lesions must have decreased by \> 75%, be gallium or positron emission tomography (PET) negative (if obtained) and be stable for \> 3 months without new lesions appearing. PR is 50% or greater decrease in the sum of the products of the diameters of all measurable lesions for at least one month. Disease progression is 25% or greater progression in the sum of the products of the diameter of any measurable lesion over one month or the appearance or any new lesion consistent with metastatic disease. Disease stabilization is no change in the sum of the products of the diameters of all measurable lesions over two months and no new lesions consistent with disease.
Time frame: From study enrollment and throughout treatment, up to a maximum of 40 months for the 2 interferon groups and 8 months for the 2 EPOCH-R groups.
Population: 9/94 participants were not analyzed because 5 were enrolled and not treated,3 participants died prior to restaging scans, and 1 was treated with rituximab and radiation only.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants Treated With Initial Interferon Therapy | Overall Response Rate (ORR) | Disease Progression | 32.76 percentage of participants |
| Participants Treated With Initial Interferon Therapy | Overall Response Rate (ORR) | Partial Remission | 5.17 percentage of participants |
| Participants Treated With Initial Interferon Therapy | Overall Response Rate (ORR) | Complete Remission | 53.45 percentage of participants |
| Participants Treated With Initial Interferon Therapy | Overall Response Rate (ORR) | Disease Stabilization | 8.62 percentage of participants |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Overall Response Rate (ORR) | Partial Remission | 25.93 percentage of participants |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Overall Response Rate (ORR) | Disease Progression | 11.11 percentage of participants |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Overall Response Rate (ORR) | Disease Stabilization | 11.11 percentage of participants |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Overall Response Rate (ORR) | Complete Remission | 51.85 percentage of participants |
| Treated With Interferon&Crossed Over - Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab | Overall Response Rate (ORR) | Partial Remission | 14.29 percentage of participants |
| Treated With Interferon&Crossed Over - Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab | Overall Response Rate (ORR) | Disease Stabilization | 14.29 percentage of participants |
| Treated With Interferon&Crossed Over - Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab | Overall Response Rate (ORR) | Disease Progression | 14.29 percentage of participants |
| Treated With Interferon&Crossed Over - Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab | Overall Response Rate (ORR) | Complete Remission | 57.14 percentage of participants |
| Treated With Pednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab&Crossed Over to Interferon | Overall Response Rate (ORR) | Disease Progression | 20.00 percentage of participants |
| Treated With Pednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab&Crossed Over to Interferon | Overall Response Rate (ORR) | Disease Stabilization | 20.00 percentage of participants |
| Treated With Pednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab&Crossed Over to Interferon | Overall Response Rate (ORR) | Complete Remission | 50.00 percentage of participants |
| Treated With Pednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab&Crossed Over to Interferon | Overall Response Rate (ORR) | Partial Remission | 10.00 percentage of participants |
Primary
Progression Free Survival (PFS)
PFS is defined as the duration of time from the date of study enrollment until the date of disease relapse, disease progression, death, or last follow-up, whichever occurs first, using the Kaplan-Meier method. Response was assessed by the Lugano Classification Response Criteria for Non-Hodgkin lymphoma (NHL). Disease progression is defined as an increase of ≥ 50% from the product of the perpendicular diameter (PPD) nadir and an increase in longest transverse diameter of a lesion (LDi) or shortest axis perpendicular diameter (SDi) from nadir of \>0.5 cm for lesions \<2 cm or \>1.0 cm for lesions \>2 cm.
Time frame: Assessed from date of study enrollment until time of disease relapse, disease progression, death, or last follow-up, whichever comes first, up to a maximum of 27 years for the 2 interferon groups and 20 years for the 2 EPOCH-R groups.
Population: 6/94 participants were not analyzed because 5 were enrolled and not treated, and 1 was treated with rituximab and radiation only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Treated With Initial Interferon Therapy | Progression Free Survival (PFS) | 1.01 years |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Progression Free Survival (PFS) | 0.69 years |
| Treated With Interferon&Crossed Over - Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab | Progression Free Survival (PFS) | 0.23 years |
| Treated With Pednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab&Crossed Over to Interferon | Progression Free Survival (PFS) | 0.53 years |
Secondary
Overall Survival (OS)
OS is defined as the time from treatment start date until date of death or date last known alive. The median OS will be determined and reported along with a 95% confidence interval.
Time frame: Assessed from date of study enrollment until time of death or last follow-up, whichever comes first, up to a maximum of 27 years.
Population: 6/94 participants were not analyzed because 5 were enrolled and not treated and 1 was treated with rituximab and radiation only.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Participants Treated With Initial Interferon Therapy | Overall Survival (OS) | 12.22 years |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Overall Survival (OS) | 9.84 years |
| Treated With Interferon&Crossed Over - Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab | Overall Survival (OS) | 8.43 years |
| Treated With Pednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab&Crossed Over to Interferon | Overall Survival (OS) | 12.13 years |
Other Pre-specified
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0)
Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Toxicity Criteria (CTC v2.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Time frame: Adverse Events were monitored/assessed from the first study intervention, Study Day 1 of Cycle 1 through 30 days after the study agent (s) was/were administered, up to a maximum of 49 months.
Population: 5 participants who were followed and not treated on study were followed for survival and mortality.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Participants Treated With Initial Interferon Therapy | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | 57 Participants |
| Treated With Initial Etoposide,Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab Therapy | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | 28 Participants |
| Treated With Interferon&Crossed Over - Prednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | 0 Participants |
| Treated With Pednisone,Vincristine,Cyclophosphamide,Doxorubicin,Rituximab&Crossed Over to Interferon | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | 1 Participants |
| Participants Treated With Cross-over Interferon | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | 10 Participants |
| Participants Treated With Cross-over EPOCH-R | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | 24 Participants |