EPOCH and Rituximab to Treat Non-Hodgkin's Lymphoma in Patients With HIV Infection

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00006436
• Collaborator: (none)
• Enrollment: 68
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 314
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, AIDS-related; Lymphoma, Large B-Cell, Diffuse	Biological: Rituximab; Biological: Filgrastim; Drug: EPOCH	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Short-Course EPOCH - Rituximab in Untreated CD-20+ HIV-Associated Lymphomas
• Actual Study Start Date: Jan 29, 2001
• Actual Primary Completion Date: Nov 30, 2020
• Anticipated Study Completion Date: Mar 30, 2027

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm 1-Combination Chemo and Biological Therapy Combination chemo and biological therapy

Biological: Rituximab; 2 doses of rituximab every cycle: first dose on Day 1 and 2nd dose on Day 5; Other Names: Rituxan ; Biological: Filgrastim; Filgrastim day 6 until absolute neutrophil count (ANC) reaches 5000 after the nadir, every cycle; Other Names: Neupogen ; Drug: EPOCH; combination chemotheray: EPOCH every 3 weeks for minimum of 3 cycles and max of 6 cycles; Other Names: etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin hydrochloride

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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).

Secondary Outcome Measures

1. 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.

2. 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.

3. 1 Year Overall Survival [1 year]

   Overall survival is time from treatment start date until date of death or date last known alive.

4. 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.

5. 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.

6. 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.

7. 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).

8. 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.

9. 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).

10. 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.

11. 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.

12. 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.

13. 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.

Other Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Mark J Roschewski, M.D., National Cancer Institute (NCI)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 17, 2021
• Informed Consent Form - Mar 31, 2021

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

None provided.

• Responsible Party: Mark Roschewski, M.D., Principal Investigator, National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00006436
• Other Study ID Numbers: 010030; 01-C-0030; NCT00020384
• First Posted: Nov 6, 2000
• Last Update Posted: Aug 16, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Mark Roschewski, M.D., Principal Investigator, National Cancer Institute (NCI): AIDS; Malignancy; Antiretroviral; Chemotherapy; Monoclonal
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, AIDS-Related; Prednisone; Cyclophosphamide; Rituximab; Doxorubicin; Etoposide; Vincristine; Liposomal doxorubicin

Study Results

Participant Flow

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Period Title: Overall Study
STARTED	68
COMPLETED	65
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Overall Participants	68
Age (Count of Participants)
<=18 years	2 2.9%
Between 18 and 65 years	66 97.1%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42.36 (10.7)
Sex: Female, Male (Count of Participants)
Female	11 16.2%
Male	57 83.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 8.8%
Not Hispanic or Latino	62 91.2%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 2.9%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	32 47.1%
White	31 45.6%
More than one race	0 0%
Unknown or Not Reported	3 4.4%
Region of Enrollment (Count of Participants)
United States	68 100%

Outcome Measures

1. Primary Outcome

Title	Median Progression Free Survival (PFS)
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Median (95% Confidence Interval) [years]	13.8

2. Primary Outcome

Title	Progression Free Survival at 1 Year
Description	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

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Number (95% Confidence Interval) [percentage of participants]	79.1 116.3%

3. Secondary Outcome

Title	Number of Participants With ≥ Grades 3-5 Non-hematologic Toxicity
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Grade 3	Grade 4	Grade 5
Arm/Group Description	Grade 3 is serious.	Grade 4 is life threatening.	Grade 5 is death related to adverse event.
Measure Participants	67	67	67
Serious infection	17 25%	0 NaN	0 NaN
Neurologic event	0 0%	0 NaN	0 NaN
Syncope	1 1.5%	0 NaN	0 NaN
Confusion	1 1.5%	0 NaN	0 NaN
Motor neuropathy	0 0%	1 NaN	0 NaN
Vision disturbance	1 1.5%	0 NaN	0 NaN
Hyperglycemia	4 5.9%	0 NaN	0 NaN
Hypophosphatemia	2 2.9%	1 NaN	0 NaN
Hypocalcemia	2 2.9%	0 NaN	0 NaN
Hypokalemia	1 1.5%	1 NaN	0 NaN
Hyponatremia	1 1.5%	0 NaN	0 NaN
Dehydration	1 1.5%	0 NaN	0 NaN
Mucositis/Stomatitis	6 8.8%	0 NaN	0 NaN
Liver test abnormalities	6 8.8%	1 NaN	0 NaN
Pancreatitis	1 1.5%	0 NaN	0 NaN
Diarrhea	2 2.9%	0 NaN	0 NaN
Constipation	1 1.5%	0 NaN	0 NaN
Serious hemorrhage	5 7.4%	1 NaN	0 NaN
Fatigue	2 2.9%	0 NaN	0 NaN
Headache	5 7.4%	0 NaN	0 NaN
Bone pain	1 1.5%	0 NaN	0 NaN
Nausea	0 0%	1 NaN	0 NaN
Anorexia	0 0%	1 NaN	0 NaN
Hypoxia	0 0%	4 NaN	1 NaN
Myelodysplastic syndrome	0 0%	0 NaN	1 NaN

4. Secondary Outcome

Title	Median Overall Survival
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Median (95% Confidence Interval) [years]	14.2

5. Secondary Outcome

Title	1 Year Overall Survival
Description	Overall survival is time from treatment start date until date of death or date last known alive.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Number (95% Confidence Interval) [percentage of participants]	83.7 123.1%

6. Secondary Outcome

Title	Median Duration of Complete Response/Complete Response Unconfirmed
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Median (95% Confidence Interval) [years]	13.9

7. Secondary Outcome

Title	Percentage of Participants With CR/CRu Lasting 1 Year
Description	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

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Number (95% Confidence Interval) [percentage of participants]	82.5 121.3%

8. Secondary Outcome

Title	Number of Participants With at Least One Hematologic Toxicity Event of Febrile Neutropenia
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Count of Participants [Participants]	18 26.5%

9. Secondary Outcome

Title	Number of Cycles of Hematologic Toxicity
Description	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)

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Febrile neutropenia	25
Neutropenia with a Nadir <500 cells/mm^3	112
Neutropenia with a Nadir <100 cells/mm^3	77
Thrombocytopenia with a Nadir <50,000 platelets/mm^3	40
Thrombocytopenia with a Nadir <25,000 platelets/mm^3	6
Anemia: hemoglobin <8 g/dL	36

10. Secondary Outcome

Title	Overall Response
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started, and one participant was not evaluable.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	66
Complete Response	53 77.9%
Complete Response Unconfirmed	10 14.7%
Partial Response	1 1.5%
Non-Responder - Stable Disease	1 1.5%
Non-Responder - Progressive Disease	1 1.5%

11. Secondary Outcome

Title	Percentage of Participants With Complete Response
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started, and one participant was not evaluable.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	66
Number [percentage of participants]	95 139.7%

12. Secondary Outcome

Title	Median Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS)
Description	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.

Outcome Measure Data

Analysis Population Description

27 participants had no PET scan.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	41
Interim PET positive participants	10.2
Interim PET negative participants	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1-Combination Chemo and Biological Therapy
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Two-tailed log rank test
	Comments
Other Statistical Analysis		Compared the PFS of interim PET positive participants to the PFS of interim PET negative.

13. Secondary Outcome

Title	1 Year Interim Positron Emission Tomography (PET) Positive Progression Free Survival (PFS)
Description	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

Outcome Measure Data

Analysis Population Description

27 participants had no PET scan.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	41
Interim PET scan positive 1-year PFS	61.5 90.4%
Interim PET scan negative 1 year PFS	89.3 131.3%

14. Secondary Outcome

Title	Recovery of CD4 T Cells (CD4) Counts
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Median (Full Range) [months]	2.5

15. Secondary Outcome

Title	Recovery of Human Immunodeficiency Virus (HIV) Viral Load
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Median (Full Range) [months]	2

16. Other Pre-specified Outcome

Title	Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Toxicity Criteria (CTC v2.0)
Description	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.

Outcome Measure Data

Analysis Population Description

One participant declined to participate before treatment started.

Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
Measure Participants	67
Count of Participants [Participants]	66 97.1%

Adverse Events

Time Frame	Date treatment consent signed to date off study, approximately 209 months and 17 days.
Adverse Event Reporting Description	One participant declined to participate before treatment started.
Arm/Group Title	Arm 1-Combination Chemo and Biological Therapy
Arm/Group Description	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
All Cause Mortality
	Arm 1-Combination Chemo and Biological Therapy
	Affected / at Risk (%)	# Events
Total	12/67 (17.9%)
Serious Adverse Events
	Arm 1-Combination Chemo and Biological Therapy
	Affected / at Risk (%)	# Events
Total	23/67 (34.3%)
Blood and lymphatic system disorders
Platelets	2/67 (3%)	2
Cardiac disorders
Cardiovascular/Arrhythmia-Other (Asystole)	1/67 (1.5%)	1
Edema	1/67 (1.5%)	1
Eye disorders
Vision-blurred vision	2/67 (3%)	2
Vision-photophobia	1/67 (1.5%)	1
Gastrointestinal disorders
Anorexia	1/67 (1.5%)	1
Constipation	2/67 (3%)	2
Dehydration	1/67 (1.5%)	1
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	1/67 (1.5%)	1
Melena/GI bleeding	1/67 (1.5%)	1
Nausea	2/67 (3%)	2
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	1/67 (1.5%)	1
Vomiting	1/67 (1.5%)	1
General disorders
Abdominal pain or cramping	1/67 (1.5%)	1
Constitutional Symptoms-Other (Death- Accident/Overdose)	1/67 (1.5%)	1
Infections and infestations
Febrile neutropenia	6/67 (9%)	9
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)	3/67 (4.5%)	3
Infection without neutropenia	3/67 (4.5%)	3
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)	1/67 (1.5%)	1
Hypophosphatemia	1/67 (1.5%)	1
Musculoskeletal and connective tissue disorders
Bone pain	1/67 (1.5%)	1
Muscle weakness (not due to neuropathy)	1/67 (1.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary Malignancy	1/67 (1.5%)	1
Secondary Malignancy-Other (Myelodysplasia/Leukemia) excludes metastasis from initial primary	2/67 (3%)	2
Nervous system disorders
CNS hemorrhage/bleeding	3/67 (4.5%)	3
Headache	4/67 (6%)	4
Neuropathy - motor	1/67 (1.5%)	1
Seizure(s)	1/67 (1.5%)	1
Renal and urinary disorders
Creatinine	1/67 (1.5%)	2
Respiratory, thoracic and mediastinal disorders
Hemorrhage-Other (alveolar)	1/67 (1.5%)	1
Hypoxia	1/67 (1.5%)	2
Pneumothorax	1/67 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Arm 1-Combination Chemo and Biological Therapy
	Affected / at Risk (%)	# Events
Total	66/67 (98.5%)
Blood and lymphatic system disorders
Hemoglobin	60/67 (89.6%)	157
Leukocytes (total WBC)	61/67 (91%)	193
Lymphopenia	58/67 (86.6%)	169
Neutrophils/granulocytes (ANC/AGC)	62/67 (92.5%)	178
Platelets	56/67 (83.6%)	138
Transfusion: Platelets	12/67 (17.9%)	48
Transfusion: pRBCs	25/67 (37.3%)	69
Cardiac disorders
Cardiovascular/Arrhythmia-Other (Tachycardia)	1/67 (1.5%)	1
Edema	5/67 (7.5%)	5
Hypertension	2/67 (3%)	2
Hypotension	7/67 (10.4%)	9
Palpitations	2/67 (3%)	2
Sinus tachycardia	6/67 (9%)	7
Thrombosis/embolism	5/67 (7.5%)	5
Ear and labyrinth disorders
Earache (otalgia)	1/67 (1.5%)	1
Inner ear/hearing	1/67 (1.5%)	1
Endocrine disorders
Dry eye	1/67 (1.5%)	1
Hypothyroidism	1/67 (1.5%)	1
Eye disorders
Conjunctivitis	1/67 (1.5%)	1
Pain-Other (pain behind eye)	1/67 (1.5%)	1
Tearing (watery eyes)	2/67 (3%)	2
Vision-blurred vision	4/67 (6%)	4
Vision-flashing lights/floaters	1/67 (1.5%)	1
Vision-photophobia	4/67 (6%)	4
Gastrointestinal disorders
Abdominal pain or cramping	10/67 (14.9%)	10
Anorexia	17/67 (25.4%)	23
Constipation	25/67 (37.3%)	38
Dehydration	5/67 (7.5%)	7
Diarrhea patients without colostomy	28/67 (41.8%)	45
Dyspepsia/heartburn	5/67 (7.5%)	6
Dysphagia, esophagitis, odynophagia (painful swallowing)	3/67 (4.5%)	3
Flatulence	5/67 (7.5%)	6
Gastrointestinal-Other (Appendicitis-Appendectomy performed)	1/67 (1.5%)	1
Gastrointestinal-Other (Fecal incontinence)	1/67 (1.5%)	1
Hematemesis	1/67 (1.5%)	1
Hemorrhage/bleeding without grade 3 or 4 thrombocytopenia	2/67 (3%)	2
Hemorrhage-Other (Hemorrhage, GI)	1/67 (1.5%)	1
Ileus (or neuroconstipation)	1/67 (1.5%)	1
Nausea	33/67 (49.3%)	62
Pain-Other (Tooth pain)	1/67 (1.5%)	1
Pain-Other (Epigastric pain)	1/67 (1.5%)	1
Pain-Other (Tooth abscess)	1/67 (1.5%)	1
Proctitis	1/67 (1.5%)	1
Rectal bleeding/hematochezia	3/67 (4.5%)	3
Rectal or perirectal pain (proctalgia)	4/67 (6%)	4
Stomatitis/pharyngitis (oral/pharyngeal mucositis)	36/67 (53.7%)	61
Taste disturbance (dysgeusia)	12/67 (17.9%)	16
Vomiting	28/67 (41.8%)	44
General disorders
Fatigue (lethargy, malaise, asthenia)	32/67 (47.8%)	57
Fever (in the absence of neutropenia, where neutropenia is defined as AGC<1.0 x 10e9/L)	14/67 (20.9%)	18
Pain-Other (bone marrow (BM) biopsy site)	1/67 (1.5%)	1
Pain-Other (Pain at port site)	1/67 (1.5%)	1
Pain-Other (Right hip hematoma)	1/67 (1.5%)	1
Pain-Other (Generalized)	1/67 (1.5%)	1
Rigors, chills	6/67 (9%)	7
Sweating (diaphoresis)	6/67 (9%)	6
Weight gain	1/67 (1.5%)	1
Weight loss	10/67 (14.9%)	11
Hepatobiliary disorders
Alkaline phosphatase	22/67 (32.8%)	34
Bilirubin	16/67 (23.9%)	20
SGOT (AST) (serum glutamic oxaloacetic transaminase)	31/67 (46.3%)	54
SGPT (ALT) (serum glutamic pyruvic transaminase)	33/67 (49.3%)	62
Immune system disorders
Allergic reaction/hypersensitivity (including drug fever)	1/67 (1.5%)	1
Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)	9/67 (13.4%)	9
Infections and infestations
Febrile neutropenia	17/67 (25.4%)	21
Infection	19/67 (28.4%)	26
Infection without neutropenia	21/67 (31.3%)	39
Infection/Febrile Neutropenia-Other (Infection with Grade 2 neutropenia)	1/67 (1.5%)	1
Investigations
Partial thromboplastin time (PTT)	10/67 (14.9%)	11
Prothrombin time (PT)	2/67 (3%)	2
Metabolism and nutrition disorders
Amylase	3/67 (4.5%)	5
Bicarbonate	8/67 (11.9%)	9
CPK (creatine phosphokinase)	3/67 (4.5%)	3
Hypercalcemia	2/67 (3%)	2
Hypercholesterolemia	1/67 (1.5%)	1
Hyperglycemia	29/67 (43.3%)	50
Hyperkalemia	4/67 (6%)	5
Hypermagnesemia	8/67 (11.9%)	9
Hypernatremia	4/67 (6%)	4
Hyperuricemia	5/67 (7.5%)	6
Hypoalbuminemia	25/67 (37.3%)	35
Hypocalcemia	25/67 (37.3%)	31
Hypoglycemia	6/67 (9%)	8
Hypokalemia	16/67 (23.9%)	27
Hypomagnesemia	27/67 (40.3%)	44
Hyponatremia	25/67 (37.3%)	41
Hypophosphatemia	14/67 (20.9%)	17
Lipase	1/67 (1.5%)	2
Musculoskeletal and connective tissue disorders
Arthralgia (joint pain)	4/67 (6%)	5
Bone pain	30/67 (44.8%)	44
Chest pain (non-cardiac and non-pleuritic)	7/67 (10.4%)	8
Muscle weakness (not due to neuropathy)	5/67 (7.5%)	7
Myalgia (muscle pain)	14/67 (20.9%)	15
Pain-Other (Back pain)	3/67 (4.5%)	4
Pain-Other (Neck pain)	1/67 (1.5%)	1
Pain-Other (Pain -Other (sacral))	1/67 (1.5%)	2
Pain-Other (Pain - Other (lower back))	1/67 (1.5%)	1
Pain-Other (Myositis)	1/67 (1.5%)	1
Pain-Other (Left leg pain_)	1/67 (1.5%)	1
Pain-Other (Leg and back pain)	1/67 (1.5%)	1
Pain-Other (Back)	2/67 (3%)	2
Pain-Other (Mild left side plank pain)	1/67 (1.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain (onset or exacerbation of tumor pain due to treatment)	1/67 (1.5%)	1
Nervous system disorders
Confusion	1/67 (1.5%)	1
Dizziness/lightheadedness	9/67 (13.4%)	11
Extrapyramidal/involuntary movement/restlessness	1/67 (1.5%)	1
Hallucinations	1/67 (1.5%)	1
Headache	30/67 (44.8%)	47
Insomnia	10/67 (14.9%)	13
Memory loss	1/67 (1.5%)	1
Mood alteration-anxiety, agitation	3/67 (4.5%)	6
Mood alteration-depression	8/67 (11.9%)	10
Neuropathic pain	2/67 (3%)	4
Neuropathy-sensory	31/67 (46.3%)	54
Seizure(s)	1/67 (1.5%)	1
Syncope (fainting)	2/67 (3%)	2
Renal and urinary disorders
Creatinine	6/67 (9%)	7
Dysuria (painful urination)	1/67 (1.5%)	1
Hematuria (in the absence of vaginal bleeding)	2/67 (3%)	2
Incontinence	2/67 (3%)	2
Proteinuria	1/67 (1.5%)	1
Renal/Genitourinary-Other (Vaginal blisters)	1/67 (1.5%)	1
Tumor lysis syndrome	1/67 (1.5%)	1
Urinary frequency/urgency	5/67 (7.5%)	5
Urinary retention	1/67 (1.5%)	1
Reproductive system and breast disorders
Erectile impotence	1/67 (1.5%)	1
Irregular menses (change from baseline)	1/67 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Cough	16/67 (23.9%)	19
Dyspnea (shortness of breath)	14/67 (20.9%)	17
Epistaxis	5/67 (7.5%)	5
Hiccoughs (hiccups, singultus)	1/67 (1.5%)	1
Pneumonitis/pulmonary infiltrates	1/67 (1.5%)	3
Voice changes/stridor/larynx (e.g., hoarseness, loss of voice, laryngitis)	1/67 (1.5%)	1
Skin and subcutaneous tissue disorders
Alopecia	26/67 (38.8%)	28
Bruising (in absence of grade 3 or 4 thrombocytopenia)	1/67 (1.5%)	1
Dermatology/Skin-Other (BACTBRABAN)	1/67 (1.5%)	1
Dermatology/Skin-Other (Blisters on hands & feet)	1/67 (1.5%)	1
Dermatology/Skin-Other (Left leg erythema)	1/67 (1.5%)	1
Dermatology/Skin-Other (Erythema derm other)	1/67 (1.5%)	1
Dry skin	1/67 (1.5%)	1
Flushing	1/67 (1.5%)	1
Nail changes	5/67 (7.5%)	9
Pigmentation changes (e.g., vitiligo)	3/67 (4.5%)	4
Pruritus	4/67 (6%)	4
Rash/desquamation	9/67 (13.4%)	11

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.