Lymphoma, AIDS-related, Lymphoma, Large B-Cell, Diffuse
Conditions
Keywords
AIDS, Malignancy, Antiretroviral, Chemotherapy, Monoclonal
Brief summary
Background: * Human immunodeficiency virus (HIV)-infected patients have a weakened immune system, and chemotherapy, which is used to treat lymphoma, probably causes further damage to the immune system. * Limiting the amount of immune damage due to chemotherapy might decrease the number of infections and the risk of developing cancer in the future in HIV-infected patients with non-Hodgkin's lymphoma. Objectives: * To determine whether reducing the total amount of chemotherapy using a specific combination of drugs called EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide and rituximab) will rid the body of lymphoma quickly while decreasing the risk of infections and future cancers. * To determine whether the lymphoma will remain undetectable for at least one year if treatment is stopped one cycle after the patient enters remission. Eligibility: -Patients with non-Hodgkin's lymphoma and HIV infection 4 years of age and older who have not been treated previously with rituximab or cytotoxic chemotherapy. Design: * Patients receive EPOCH-R in 3-week treatment cycles for at least three and no more than six cycles. * The lymphoma is evaluated using computed tomography (CT) and positron emission tomography (PET) scans at the end of treatment cycles 2 and 3. A bone marrow biopsy is repeated after cycle 2 if a biopsy was initially positive on screening for participation in the study. * Anti-HIV therapy is stopped before chemotherapy begins and is restarted when EPOCH-R treatment ends. * Patients are monitored for treatment response with blood tests and imaging scans at baseline, when treatment ends, 2 months after treatment ends and then every 3 to 6 months for a total of 24 months following chemotherapy.
Detailed description
Background: This is a study to investigate in a preliminary fashion the feasibility of short course chemotherapy to participants with HIV-associated non-Hodgkin's lymphoma (HIV-NHL). This study will investigate if the paradigm for treatment can be successfully changed from a standard of 6 cycles to one cycle beyond complete remission with 6 total allowable cycles. Objective: To assess with 90 percent probability that at least 50 percent of participants treated with short-course EPOCH-R (etoposide, doxorubicin, vincristine, cyclophosphamide and rituximab) will be progression free at one year. Eligibility: Aggressive B-lymphocyte antigen CD20 (CD20) positive Diffuse large B cell lymphoma (DLBCL). HIV+ serology. All stages (I-IV) of disease. Eastern Cooperative Oncology Group (ECOG) Performance status 0-4. Non-Hodgkin's Lymphoma (NHL) previously untreated with cytotoxic chemotherapy. Age greater than or equal to 18 years. May not be pregnant or nursing. May not have received previous rituximab. Design: Participants will be treated every three weeks with a combination of EPOCH and rituximab for one cycle beyond complete remission (CR)/complete response unconfirmed (CRu) by computed tomography (CT) scan of all detectable tumors for a minimum of three and maximum of six cycles. Following cycle 2, CT, positron emission tomography scans (PET), and bone marrow biopsies (if initially positive) will be performed. At the conclusion of the study, we will estimate whether the number of cycles can be reduced using the paradigm. If the cumulative number of participants to relapse exceeds 25 percent by 6 months, the study will be closed. Following the completion of chemotherapy, restaging will be performed 2 months following the end of treatment, then every 3 months for one year, every 6 months for one year, then every 12 months until relapse, death, or loss to follow up. Antiretroviral therapy (ART) will be given concurrently with treatment regimen. To study the effects of treatment approach on parameters of HIV disease, measurements of cluster of differentiation 4 (CD4) cells and viral loads will be made at baseline and at the completion of therapy, and then 2 months following the end of treatment, and then every 3-6 months for a total of 24 months following chemotherapy.
Interventions
BIOLOGICALRituximab
2 doses of rituximab every cycle: first dose on Day 1 and 2nd dose on Day 5
BIOLOGICALFilgrastim
Filgrastim day 6 until absolute neutrophil count (ANC) reaches 5000 after the nadir, every cycle
DRUGEPOCH
combination chemotheray: EPOCH every 3 weeks for minimum of 3 cycles and max of 6 cycles
Sponsors
National Cancer Institute (NCI)
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
* INCLUSION CRITERIA: Aggressive B-lymphocyte antigen CD20 (CD20) positive Diffuse Large B-cell lymphoma confirmed by Laboratory of Pathology, National Cancer Institute (NCI). Note: Participants with aggressive B-cell lymphoma of the plasmablastic lymphoma sub-type who do not have surface CD20 expression, are also eligible. Human immunodeficiency virus (HIV) + serology. All stages (I-IV) of disease. Eastern Cooperative Oncology Group (ECOG) Performance status 0-4 Non-Hodgkin's Lymphoma (NHL) previously untreated with cytotoxic chemotherapy; however, participants may be entered if they have had prior cyclophosphamide for an urgent problem at diagnosis (e.g., epidural cord compression, superior vena cava syndrome) and/or a single dose of intrathecal methotrexate (MTX) at the time of the pre-treatment diagnostic lumbar puncture Age greater than or equal to 18 years Laboratory tests (unless impairment due to respective organ involvement by tumor): * Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than or equal to 50 ml/min * Bilirubin less than 2.0 mg/dl, or total bilirubin less than or equal to 4.5 mg/dl with direct fraction less than or equal to 0.3 mg/dl in participants for whom these abnormalities are felt to be due to protease inhibitor therapy * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3x upper limit of normal (ULN) (AST and ALT less than or equal to 6x ULN for participants on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation) * Absolute neutrophil count (ANC) greater than or equal to 1000/mm(3) * Platelet greater than or equal to 75,000/mm(3) (unless impairment due to Immune thrombocytopenic purpura (ITP) Ability of participant to provide informed consent.
Exclusion criteria
Previous rituximab Pregnancy or nursing. \- Doxorubicin, etoposide, vincristine and cyclophosphamide are teratogenic and may be excreted in milk. Current clinical heart failure or symptomatic ischemic heart disease. Serious underlying medical condition or infection other than HIV that would contraindicate subcutaneous (SC)-rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (hydroxydaunorubicin (EPOCH-R). * Examples include, but are not limited to: * Severe Acquired immunodeficiency syndrome (AIDS)-related wasting * Sever intractable diarrhea * Active inadequately treated opportunistic infection of the central nervous system (CNS) * Primary CNS lymphoma Primary CNS lymphoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival at 1 Year | 1 year | PFS is the time interval from start of treatment to documented evidence of disease progression. Progression is defined according to the Cheson response criteria. Disease progression as indicated by imaging scans at one year following therapy. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s). |
| Median Progression Free Survival (PFS) | The participants were followed for a median of 15.4 years. | PFS is the time interval from study entry to documented evidence of disease progression or death due to any cause. Progression is defined according to the Cheson response criteria. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s). Confidence intervals were made, and a Kaplan-Meier curve of progression free survival was constructed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Median Overall Survival | The participants were followed for survival for a median of 15.4 years. | Overall survival is time from treatment start date until date of death or date last known alive. |
| 1 Year Overall Survival | 1 year | Overall survival is time from treatment start date until date of death or date last known alive. |
| Median Duration of Complete Response/Complete Response Unconfirmed | The participants were followed for duration of complete response or complete response unconfirmed for a median of 15.4 years. | Complete response (CR) was assessed by the Cheson response criteria. Complete response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size (1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy). Complete response unconfirmed (CRu) is when a residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by \> 75% in sum of the products of the greatest diameters, does not change over the last two treatments, and any biopsies obtained are negative will be considered to be in CR. In organs involved by disease, any residual lesions that have decreased by \> 75% in sum of the products of the greatest diameters or are \< 1 cm, are consistent with scar, and stable over the last two treatments will be considered to fulfill criteria for CR. |
| Percentage of Participants With CR/CRu Lasting 1 Year | 1 year | Complete response (CR) was assessed by the Cheson response criteria. Complete response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size (1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy). Complete response unconfirmed (CRu) is when a residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by \> 75% in sum of the products of the greatest diameters, does not change over the last two treatments, and any biopsies obtained are negative will be considered to be in CR. In organs involved by disease, any residual lesions that have decreased by \> 75% in sum of the products of the greatest diameters or are \< 1 cm, are consistent with scar, and stable over the last two treatments will be considered to fulfill criteria for CR. |
| Number of Participants With at Least One Hematologic Toxicity Event of Febrile Neutropenia | Date treatment consent signed to date off study, approximately 209 months and 17 days. | Toxicity was assessed by the Common Toxicity Criteria (CTC v2.0). Febrile neutropenia is defined as a life-threatening complication requiring hospitalization and urgent broad-spectrum antibiotics. |
| Number of Cycles of Hematologic Toxicity | Up to 112 cycles (each cycle is 21 days + 7 days window) | Cumulative number of cycles of hematologic toxicity. Hematologic (i.e., decrease in bone marrow and blood cells) toxicity was assessed by the Common Toxicity Criteria (CTC v2.0). |
| Percentage of Participants With Complete Response | The participants were followed for an average of 6 months to determine response to therapy. | Complete response was assessed by the Cheson Response Criteria. Complete response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size (1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy). |
| Median Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS) | Participants were followed for up to 10.2 years to determine their response on interim PET scans. | PFS is the time interval from start of treatment to documented evidence of disease progression or death from any cause. Disease progression was assessed by positron emission tomography scans after 2 cycles (each cycle is 21 days + 7 days window) of therapy using the Deauville criteria. Deauville score of 4 or 5 is considered positive on interim PET scan while a Deauville score of 1 or 2 or 3 is considered negative. The outcomes of the Deauville score was compared to determine PET positive progression free survival. |
| 1 Year Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS) | 1 year | 1-year PFS is defined as participants who remain free of disease progression or death at one year from study entry. We compared the 1-year PFS of participants with negative results on interim positron emission tomography (PET) scans to those with positive results on interim PET scans. PFS is defined as the time interval from start of treatment to documented evidence of disease progression or death from any cause. Disease progression was assessed by positron emission tomography scans after 2 cycles of therapy using the Deauville criteria. Deauville score of 4 or 5 is considered positive on interim PET scan while a Deauville score of 1 or 2 or 3 is considered negative. The outcomes of the Deauville score was compared to determine PET positive progression free survival. |
| Recovery of CD4 T Cells (CD4) Counts | From the end of chemotherapy every 3 months for the first 2 years | Participants with human immunodeficiency virus (HIV) who undergo chemotherapy may have a delay in the recovery of their normal CD4+ T-cells. This delay could result in an increased risk of infection. Recovery of CD4 cells counts is the time from end of therapy until the time that the CD4 counts first reached above 200 cells/uL. |
| Recovery of Human Immunodeficiency Virus (HIV) Viral Load | Either following or concurrently with combination chemo and biological therapy, approximately every 6 to 8 weeks after therapy was completed up to 16 months | The HIV viral load is a measure of actively replicating virus in the blood. If no anti-retroviral therapy is given, then reduction of this HIV viral load to manageable levels might risk infection. In our study, the recovery of HIV viral load was measured the time from the initiation of antiretroviral therapy until the viral load was undetectable or \< 50 copies. |
| Overall Response | The participants were followed for an average of 6 months to determine response to therapy. | Overall response was determined by the Cheson Response Criteria. Participants with either a complete response (CR), complete response unconfirmed or partial response were considered responders. Less than a partial response was considered a non-response to therapy (i.e., Stable Disease and/or Progressive Disease). Complete response was defined as the disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size. Complete response unconfirmed is a residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by \> 75% in sum of the products of the greatest diameters, does not change over the last two treatments, and any biopsies obtained are negative will be considered to be in CR. Partial response is defined as a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting for a period of at least one month. |
| Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Date treatment consent signed to date off study, approximately 209 months and 17 days. | Non-hematologic (i.e., not begin in bone marrow or blood) toxicity was assessed by the Common Toxicity Criteria (CTC v2.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event. |
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) | Date treatment consent signed to date off study, approximately 209 months and 17 days. | 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 |
|---|---|
| Arm 1-Combination Chemo and Biological Therapy Combination chemo and biological therapy
Rituximab: 2 doses of rituximab every cycle: first dose on Day 1 and 2nd dose on Day 5
Filgrastim: Filgrastim day 6 until absolute neutrophil count (ANC) reaches 5000 after the nadir, every cycle
Etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride (EPOCH): combination chemotherapy: EPOCH every 3 weeks for minimum of 3 cycles and max of 6 cycles | 68 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Declined to participate (before treatment started) | 1 |
| Overall Study | Refused further treatment | 2 |
Baseline characteristics
| Characteristic | Arm 1-Combination Chemo and Biological Therapy |
|---|---|
| Age, Categorical <=18 years | 2 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 66 Participants |
| Age, Continuous | 42.36 years STANDARD_DEVIATION 10.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 32 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 | 3 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Region of Enrollment United States | 68 Participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 57 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 67 |
| other Total, other adverse events | 66 / 67 |
| serious Total, serious adverse events | 23 / 67 |
Outcome results
Primary
Median Progression Free Survival (PFS)
PFS is the time interval from study entry to documented evidence of disease progression or death due to any cause. Progression is defined according to the Cheson response criteria. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s). Confidence intervals were made, and a Kaplan-Meier curve of progression free survival was constructed.
Time frame: The participants were followed for a median of 15.4 years.
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Median Progression Free Survival (PFS) | 13.8 years |
Primary
Progression Free Survival at 1 Year
PFS is the time interval from start of treatment to documented evidence of disease progression. Progression is defined according to the Cheson response criteria. Disease progression as indicated by imaging scans at one year following therapy. Disease progression is defined as increase of 25% or more in the sum of the products of the longest perpendicular diameters of all measured lesions compared to the smallest previous measurements, or the appearance of any new lesion(s).
Time frame: 1 year
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Progression Free Survival at 1 Year | 79.1 percentage of participants |
Secondary
1 Year Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS)
1-year PFS is defined as participants who remain free of disease progression or death at one year from study entry. We compared the 1-year PFS of participants with negative results on interim positron emission tomography (PET) scans to those with positive results on interim PET scans. PFS is defined as the time interval from start of treatment to documented evidence of disease progression or death from any cause. Disease progression was assessed by positron emission tomography scans after 2 cycles of therapy using the Deauville criteria. Deauville score of 4 or 5 is considered positive on interim PET scan while a Deauville score of 1 or 2 or 3 is considered negative. The outcomes of the Deauville score was compared to determine PET positive progression free survival.
Time frame: 1 year
Population: 27 participants had no PET scan.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | 1 Year Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS) | Interim PET scan positive 1-year PFS | 61.5 percentage of participants |
| Arm 1-Combination Chemo and Biological Therapy | 1 Year Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS) | Interim PET scan negative 1 year PFS | 89.3 percentage of participants |
Secondary
1 Year Overall Survival
Overall survival is time from treatment start date until date of death or date last known alive.
Time frame: 1 year
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | 1 Year Overall Survival | 83.7 percentage of participants |
Secondary
Median Duration of Complete Response/Complete Response Unconfirmed
Complete response (CR) was assessed by the Cheson response criteria. Complete response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size (1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy). Complete response unconfirmed (CRu) is when a residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by \> 75% in sum of the products of the greatest diameters, does not change over the last two treatments, and any biopsies obtained are negative will be considered to be in CR. In organs involved by disease, any residual lesions that have decreased by \> 75% in sum of the products of the greatest diameters or are \< 1 cm, are consistent with scar, and stable over the last two treatments will be considered to fulfill criteria for CR.
Time frame: The participants were followed for duration of complete response or complete response unconfirmed for a median of 15.4 years.
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Median Duration of Complete Response/Complete Response Unconfirmed | 13.9 years |
Secondary
Median Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS)
PFS is the time interval from start of treatment to documented evidence of disease progression or death from any cause. Disease progression was assessed by positron emission tomography scans after 2 cycles (each cycle is 21 days + 7 days window) of therapy using the Deauville criteria. Deauville score of 4 or 5 is considered positive on interim PET scan while a Deauville score of 1 or 2 or 3 is considered negative. The outcomes of the Deauville score was compared to determine PET positive progression free survival.
Time frame: Participants were followed for up to 10.2 years to determine their response on interim PET scans.
Population: 27 participants had no PET scan.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Median Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS) | Interim PET positive participants | 10.2 years |
| Arm 1-Combination Chemo and Biological Therapy | Median Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS) | Interim PET negative participants | NA years |
p-value: 0.1Two-tailed log rank test
Secondary
Median Overall Survival
Overall survival is time from treatment start date until date of death or date last known alive.
Time frame: The participants were followed for survival for a median of 15.4 years.
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Median Overall Survival | 14.2 years |
Secondary
Number of Cycles of Hematologic Toxicity
Cumulative number of cycles of hematologic toxicity. Hematologic (i.e., decrease in bone marrow and blood cells) toxicity was assessed by the Common Toxicity Criteria (CTC v2.0).
Time frame: Up to 112 cycles (each cycle is 21 days + 7 days window)
Population: One participant declined to participate before treatment started.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Number of Cycles of Hematologic Toxicity | Neutropenia with a Nadir <500 cells/mm^3 | 112 cycles |
| Arm 1-Combination Chemo and Biological Therapy | Number of Cycles of Hematologic Toxicity | Febrile neutropenia | 25 cycles |
| Arm 1-Combination Chemo and Biological Therapy | Number of Cycles of Hematologic Toxicity | Neutropenia with a Nadir <100 cells/mm^3 | 77 cycles |
| Arm 1-Combination Chemo and Biological Therapy | Number of Cycles of Hematologic Toxicity | Thrombocytopenia with a Nadir <50,000 platelets/mm^3 | 40 cycles |
| Arm 1-Combination Chemo and Biological Therapy | Number of Cycles of Hematologic Toxicity | Thrombocytopenia with a Nadir <25,000 platelets/mm^3 | 6 cycles |
| Arm 1-Combination Chemo and Biological Therapy | Number of Cycles of Hematologic Toxicity | Anemia: hemoglobin <8 g/dL | 36 cycles |
Secondary
Number of Participants With at Least One Hematologic Toxicity Event of Febrile Neutropenia
Toxicity was assessed by the Common Toxicity Criteria (CTC v2.0). Febrile neutropenia is defined as a life-threatening complication requiring hospitalization and urgent broad-spectrum antibiotics.
Time frame: Date treatment consent signed to date off study, approximately 209 months and 17 days.
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With at Least One Hematologic Toxicity Event of Febrile Neutropenia | 18 Participants |
Secondary
Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity
Non-hematologic (i.e., not begin in bone marrow or blood) toxicity was assessed by the Common Toxicity Criteria (CTC v2.0). Grade 3 is severe. Grade 4 is life-threatening. Grade 5 is death related to adverse event.
Time frame: Date treatment consent signed to date off study, approximately 209 months and 17 days.
Population: One participant declined to participate before treatment started.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Confusion | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Constipation | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypokalemia | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Myelodysplastic syndrome | 0 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Serious infection | 17 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hyponatremia | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Nausea | 0 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Diarrhea | 2 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Dehydration | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Motor neuropathy | 0 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Pancreatitis | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Mucositis/Stomatitis | 6 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypoxia | 0 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Liver test abnormalities | 6 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Bone pain | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Vision disturbance | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Syncope | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Headache | 5 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hyperglycemia | 4 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Neurologic event | 0 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Fatigue | 2 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypophosphatemia | 2 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Anorexia | 0 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Serious hemorrhage | 5 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypocalcemia | 2 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Diarrhea | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Serious infection | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Neurologic event | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Syncope | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Confusion | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Motor neuropathy | 1 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Vision disturbance | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hyperglycemia | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypophosphatemia | 1 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypocalcemia | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypokalemia | 1 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hyponatremia | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Dehydration | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Mucositis/Stomatitis | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Liver test abnormalities | 1 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Pancreatitis | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Constipation | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Serious hemorrhage | 1 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Fatigue | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Headache | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Bone pain | 0 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Nausea | 1 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Anorexia | 1 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypoxia | 4 Participants |
| Grade 4 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Myelodysplastic syndrome | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Constipation | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypophosphatemia | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Serious infection | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Serious hemorrhage | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hyperglycemia | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Anorexia | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Fatigue | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Vision disturbance | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Neurologic event | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Headache | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Motor neuropathy | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Myelodysplastic syndrome | 1 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Bone pain | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Confusion | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Mucositis/Stomatitis | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypoxia | 1 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Liver test abnormalities | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Dehydration | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Nausea | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Pancreatitis | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hyponatremia | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypokalemia | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Diarrhea | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Hypocalcemia | 0 Participants |
| Grade 5 | Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity | Syncope | 0 Participants |
Secondary
Overall Response
Overall response was determined by the Cheson Response Criteria. Participants with either a complete response (CR), complete response unconfirmed or partial response were considered responders. Less than a partial response was considered a non-response to therapy (i.e., Stable Disease and/or Progressive Disease). Complete response was defined as the disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size. Complete response unconfirmed is a residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by \> 75% in sum of the products of the greatest diameters, does not change over the last two treatments, and any biopsies obtained are negative will be considered to be in CR. Partial response is defined as a 50% or greater decrease in the sum of the products of the longest perpendicular diameters of all measured lesions lasting for a period of at least one month.
Time frame: The participants were followed for an average of 6 months to determine response to therapy.
Population: One participant declined to participate before treatment started, and one participant was not evaluable.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Overall Response | Complete Response | 53 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Overall Response | Complete Response Unconfirmed | 10 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Overall Response | Partial Response | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Overall Response | Non-Responder - Stable Disease | 1 Participants |
| Arm 1-Combination Chemo and Biological Therapy | Overall Response | Non-Responder - Progressive Disease | 1 Participants |
Secondary
Percentage of Participants With Complete Response
Complete response was assessed by the Cheson Response Criteria. Complete response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size (1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy).
Time frame: The participants were followed for an average of 6 months to determine response to therapy.
Population: One participant declined to participate before treatment started, and one participant was not evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Percentage of Participants With Complete Response | 95 percentage of participants |
Secondary
Percentage of Participants With CR/CRu Lasting 1 Year
Complete response (CR) was assessed by the Cheson response criteria. Complete response is disappearance of all signs and symptoms of lymphoma for a period of at least one month. All lymph nodes and nodal masses must have regressed to normal size (1.5 cm in their greatest transverse diameter for nodes \> 1.5 cm before therapy). Complete response unconfirmed (CRu) is when a residual lymph node mass \> 1.5 cm in greatest transverse diameter that has regressed by \> 75% in sum of the products of the greatest diameters, does not change over the last two treatments, and any biopsies obtained are negative will be considered to be in CR. In organs involved by disease, any residual lesions that have decreased by \> 75% in sum of the products of the greatest diameters or are \< 1 cm, are consistent with scar, and stable over the last two treatments will be considered to fulfill criteria for CR.
Time frame: 1 year
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Percentage of Participants With CR/CRu Lasting 1 Year | 82.5 percentage of participants |
Secondary
Recovery of CD4 T Cells (CD4) Counts
Participants with human immunodeficiency virus (HIV) who undergo chemotherapy may have a delay in the recovery of their normal CD4+ T-cells. This delay could result in an increased risk of infection. Recovery of CD4 cells counts is the time from end of therapy until the time that the CD4 counts first reached above 200 cells/uL.
Time frame: From the end of chemotherapy every 3 months for the first 2 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Recovery of CD4 T Cells (CD4) Counts | 2.5 months |
Secondary
Recovery of Human Immunodeficiency Virus (HIV) Viral Load
The HIV viral load is a measure of actively replicating virus in the blood. If no anti-retroviral therapy is given, then reduction of this HIV viral load to manageable levels might risk infection. In our study, the recovery of HIV viral load was measured the time from the initiation of antiretroviral therapy until the viral load was undetectable or \< 50 copies.
Time frame: Either following or concurrently with combination chemo and biological therapy, approximately every 6 to 8 weeks after therapy was completed up to 16 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Recovery of Human Immunodeficiency Virus (HIV) Viral Load | 2 months |
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: Date treatment consent signed to date off study, approximately 209 months and 17 days.
Population: One participant declined to participate before treatment started.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Combination Chemo and Biological Therapy | Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0) | 66 Participants |