Clincosm LogoSign in Get a demo

Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Completed
CT.gov ID
NCT00118209
Collaborator
National Cancer Institute (NCI) (NIH)
524
Enrollment
47
Locations
2
Arms
198.5
Actual Duration (Months)
11.1
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

PRIMARY OBJECTIVES:

  1. To compare the event-free survival of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone (R-CHOP) versus dose-adjusted (DA-) etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, and rituximab (EPOCH-R) chemotherapy in untreated cluster of differentiation (CD)20 positive (+) diffuse large B-cell lymphomas.

  2. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling.

SECONDARY OBJECTIVES:

  1. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R.

  2. To define the pharmacogenomics of untreated diffuse large B-cell lymphoma (DLBCL) and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling.

  3. To assess the use of molecular profiling for pathological diagnosis. IV. To identify new therapeutic targets using molecular profiling. V. To perform a comprehensive analysis of somatic alterations to the tumor genome and to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.

  4. To identify biomarkers of response to chemotherapy by fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL.

  5. To evaluate the use of semiquantitative measurements of FDG uptake in defining FDG-PET/CT based biomarkers of response to chemotherapy in patients with DLBCL.

  6. To determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response.

  7. To establish a standardized protocol for FDG-PET/CT image acquisition. X. To determine additional FDG-PET/CT parameters (e.g., the ratio of tumor maximum standard uptake value [SUVmax] to liver SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine physician's assessment) and evaluate their utility in refining FDG-PET/CT based biomarkers of response to therapy.

  8. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Study Design

Study Type:
Interventional
Actual Enrollment :
524 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas
Actual Study Start Date :
May 1, 2005
Actual Primary Completion Date :
Oct 1, 2017
Actual Study Completion Date :
Nov 15, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Arm A - R-CHOP

Patients receive the following treatment: Rituximab 375 mg/m^2 IV infusion on Day 1 prior to CHOP chemotherapy Cyclophosphamide 750 mg/m^2 IV on Day 1 Doxorubicin 50 mg/m^2 IV on Day 1 Vincristine 1.4 mg/m^2 IV (2 mg cap) on Day 1 Prednisone 40 mg/m^2/day PO on Days 1-5 filgrastim or pegfilgrastim as defined in the protocol Required ancillary medications is administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.

Biological: rituximab
IV

Drug: cyclophosphamide
IV

Drug: doxorubicin
IV or CIVI

Drug: vincristine
IV or CIVI

Drug: prednisone
oral

Drug: filgrastim
IV

Drug: pegfilgrastim
IV
Experimental: Arm B - DA-EPOCH-R

Patients receive the following treatment: Cycle 1 Doses: Rituximab 375 mg/m^2 IV infusion on Day 1 prior to EPOCH chemotherapy Doxorubicin 10 mg/m^2/day CIVI on Days 1-4 Etoposide 50 mg/m^2/day CIVI on Days 1-4 Vincristine 0.4 mg/m^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours) Cyclophosphamide 750 mg/m^2 IV on Day 5 (following completion of 96 hour infusions) Prednisone 60 mg/m^2 PO BID on Days 1-5 Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC > 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle. Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle. Required ancillary medications are administered during all cycles as defined in the protocol. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.

Biological: rituximab
IV

Drug: cyclophosphamide
IV

Drug: doxorubicin
IV or CIVI

Drug: vincristine
IV or CIVI

Drug: prednisone
oral

Drug: etoposide
CIVI

Drug: filgrastim
IV

Outcome Measures

Primary Outcome Measures

  1. Progression-Free Survival Rate at 2 and 5 Years [Up to 5 years post-registration]

    Progression-free survival (PFS) is defined as the time from randomization to progression, relapse, or death from any cause, whichever occurred first. Progression (PD) or Relapse> ≥ 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders.> Appearance of any new lesion during or after completion of therapy.> PET+ is not a criterion for progressive disease. Patients only with PET+ findings must have evidence of progression on CT or biopsy proven.> The PFS rate (percentage of participants who are alive and progression-free) at 2 and 5 years Kaplan Meier estimates and 95% Confidence Intervals are reported below.

Secondary Outcome Measures

  1. Response Rate [Up to 5 years post-registration]

    The overall response rate is defined as the percentage of participants with a response (Complete Response or Partial Response)

  2. Overall Survival Rate at 2 and 5 Years [Up to 5 years post-registration]

    Overall survival is defined as the time from randomization to death due to any cause. The overall survival (OS) rate (percentage of participants who are still alive) at 2 and 5 years Kaplan Meier estimates and 95% confidence intervals are reported below.

Other Outcome Measures

  1. Whether the Gene Expression Signatures That Were Previously Associated With Survival Following CHOP Therapy Are Associated With Survival in Either of the Treatment Arms of the Prospective Trial [Up to 5 years post-registration]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
  1. Histologically documented de novo CD20+ DLBCL with stage II, III or IV disease.

  • Stage I primary mediastinal (thymic) DLBCL is also eligible.

  • Patients with an underlying low-grade lymphoma, such as a transformed lymphoma or low-grade lymphoma in the bone marrow, are not eligible.

  • Diagnosis should be based on an adequate tissue sample, including open biopsy or core needle biopsy.

  • Needle aspiration for primary diagnosis is unacceptable.

  • Patients must have one of the following WHO classification subtypes:

  • Diffuse large B-cell lymphoma (includes morphological variants: centroblastic, immunoblastic, T-cell/histiocyte rich, and anaplastic)

  • Mediastinal (thymic) large B-cell lymphoma

  • Intravascular large B-cell lymphoma

  • Note: Failure to submit a pathology block within 60 days of patient registration will be considered a major protocol violation.

  • Fresh (frozen) tumor biopsy must be available or attempted. A frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study.

  • Patients without adequate frozen material should have a biopsy performed to obtain material.

  • If a biopsy is performed and does not yield adequate material, the patient is still eligible for the study. If a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted.

  • Note: This study does not allow concurrent radiation unless a patient has a documented CNS treatment failure with no systemic failure.

  1. No prior cytotoxic chemotherapy or rituximab. Patients may be entered if they have received prior limited field radiation therapy or a short course of glucocorticoids (< 10 days) for an urgent local disease complication at diagnosis (e.g., cord compression, SVC syndrome). Patients who have received chemotherapy for prior malignancies are not eligible.

  2. Age ≥ 18 years

  3. ECOG Performance Status 0-2

  4. No active ischemic heart disease or congestive heart failure. If there is suspicion of cardiac disease, a cardiac ejection fraction must show LVEF > 45%, but the study is not required

  5. No known lymphomatous involvement of the CNS. A lumbar puncture prior to study is not required in the absence of neurological symptoms

  6. No known HIV disease. Patients with a history of intravenous drug abuse or any other behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Patients who test positive or who are known to be infected are not eligible.

  7. Non pregnant and non-nursing. Treatment would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective form of contraception.

  8. Patients with active medical processes (e.g., uncontrolled bacterial or viral infection, bleeding) not related to their lymphoma should be excluded.

  9. Required Initial Laboratory Values (unless non-Hodgkin lymphoma):

  • ANC ≥ 1000/μL

  • Platelets ≥ 100,000/μL

  • Creatinine≤ 1.5 mg/dL or creatinine clearance ≥ 50 cc/min

  • Total Bilirubin ≤ 2 mg/dL (unless a history of Gilbert's Disease)

Contacts and Locations

Locations

Site City State Country Postal Code
1 Rebecca and John Moores UCSD Cancer Center La Jolla California United States 92093-0658
2 Camino Medical Group - Treatment Center Mountain View California United States 94040
3 Palo Alto Medical Foundation Palo Alto California United States 94301
4 Saint Helena Hospital Saint Helena California United States 94574
5 Naval Medical Center - San Diego San Diego California United States 92134
6 Eastern Connecticut Hematology and Oncology Associates Norwich Connecticut United States 06360
7 CCOP - Christiana Care Health Services Newark Delaware United States 19713
8 Robert H. Lurie Comprehensive Cancer Center at Northwestern University Chicago Illinois United States 60611-3013
9 University of Illinois Cancer Center Chicago Illinois United States 60612-7243
10 Creticos Cancer Center at Advocate Illinois Masonic Medical Center Chicago Illinois United States 60657
11 Cardinal Bernardin Cancer Center at Loyola University Medical Center Maywood Illinois United States 60153
12 Alvin and Lois Lapidus Cancer Institute at Sinai Hospital Baltimore Maryland United States 21215
13 National Naval Medical Center Bethesda Maryland United States 20889-5600
14 NIH - Warren Grant Magnuson Clinical Center Bethesda Maryland United States 20892-1182
15 Providence Cancer Institute at Providence Hospital - Southfield Campus Southfield Michigan United States 48075
16 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis Saint Louis Missouri United States 63110
17 Christian Hospital Northeast-Northwest Saint Louis Missouri United States 63136
18 New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care Concord New Hampshire United States 03301
19 New Hampshire Oncology - Hematology, PA - Hooksett Hooksett New Hampshire United States 03106
20 Charles R. Wood Cancer Center at Glens Falls Hospital Glens Falls New York United States 12801
21 New York Weill Cornell Cancer Center at Cornell University New York New York United States 10021
22 James P. Wilmot Cancer Center at University of Rochester Medical Center Rochester New York United States 14642
23 Presbyterian Cancer Center at Presbyterian Hospital Charlotte North Carolina United States 28233-3549
24 Kinston Medical Specialists Kinston North Carolina United States 28501
25 Iredell Memorial Hospital Statesville North Carolina United States 28677
26 Wake Forest University Comprehensive Cancer Center Winston-Salem North Carolina United States 27157-1096
27 Altru Cancer Center at Altru Hospital Grand Forks North Dakota United States 58201
28 Mercy Cancer Center at Mercy Medical Center Canton Ohio United States 44708
29 Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Columbus Ohio United States 43210-1240
30 Geisinger Cancer Institute at Geisinger Health Danville Pennsylvania United States 17822-0001
31 Easton Regional Cancer Center at Easton Hospital Easton Pennsylvania United States 18042
32 Geisinger Hazleton Cancer Center Hazleton Pennsylvania United States 18201
33 Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center Hershey Pennsylvania United States 17033-0850
34 Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital Pittsburgh Pennsylvania United States 15224-1791
35 Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center Wilkes-Barre Pennsylvania United States 18711
36 Mountainview Medical Berlin Vermont United States 05602
37 Virginia Commonwealth University Massey Cancer Center Richmond Virginia United States 23298-0037
38 Madigan Army Medical Center - Tacoma Tacoma Washington United States 98431
39 Mary Babb Randolph Cancer Center at West Virginia University Hospitals Morgantown West Virginia United States 26506
40 Marshfield Clinic - Marshfield Center Marshfield Wisconsin United States 54449
41 Saint Joseph's Hospital Marshfield Wisconsin United States 54449
42 Marshfield Clinic - Lakeland Center Minocqua Wisconsin United States 54548
43 Ministry Medical Group at Saint Mary's Hospital Rhinelander Wisconsin United States 54501
44 Marshfield Clinic - Indianhead Center Rice Lake Wisconsin United States 54868
45 Marshfield Clinic at Saint Michael's Hospital Stevens Point Wisconsin United States 54481
46 Saint Michael's Hospital Cancer Center Stevens Point Wisconsin United States 54481
47 Marshfield Clinic - Weston Center Weston Wisconsin United States 54476

Sponsors and Collaborators

  • Alliance for Clinical Trials in Oncology
  • National Cancer Institute (NCI)

Investigators

  • Study Chair: Wyndham H. Wilson, MD, PhD, National Cancer Institute (NCI)
  • Study Chair: Andrew D. Zelenetz, MD, PhD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00118209
Other Study ID Numbers:
  • CALGB-50303
  • CDR0000433265
  • NCI-2009-00480
  • U10CA031946
  • U10CA180821
  • NCT00234351
First Posted:
Jul 11, 2005
Last Update Posted:
Nov 17, 2021
Last Verified:
Nov 1, 2021
Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Prednisone
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Vincristine

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Arm A - R-CHOP Arm B - DA-EPOCH-R
Arm/Group Description Patients receive the following treatment:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to CHOP chemotherapy> Cyclophosphamide 750 mg/m^2 IV on Day 1> Doxorubicin 50 mg/m^2 IV on Day 1> Vincristine 1.4 mg/m^2 IV (2 mg cap) on Day 1> Prednisone 40 mg/m^2/day PO on Days 1-5> filgrastim or pegfilgrastim as defined in the protocol> Required ancillary medications is administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Patients receive the following treatment:> Cycle 1 Doses:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to EPOCH chemotherapy> Doxorubicin 10 mg/m^2/day CIVI on Days 1-4> Etoposide 50 mg/m^2/day CIVI on Days 1-4> Vincristine 0.4 mg/m^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)> Cyclophosphamide 750 mg/m^2 IV on Day 5 (following completion of 96 hour infusions)> Prednisone 60 mg/m^2 PO BID on Days 1-5> Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC > 5000 after the > nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not > being monitored, during every cycle.> Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.> Required ancillary medications are administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.
Period Title: Overall Study
STARTED 262 262
Evaluable for Primary Endpoint 250 241
Evaluable for Safety Analysis 243 237
COMPLETED 250 241
NOT COMPLETED 12 21

Baseline Characteristics

Arm/Group Title Arm A - R-CHOP Arm B - DA-EPOCH-R Total
Arm/Group Description Patients receive the following treatment:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to CHOP chemotherapy> Cyclophosphamide 750 mg/m^2 IV on Day 1> Doxorubicin 50 mg/m^2 IV on Day 1> Vincristine 1.4 mg/m^2 IV (2 mg cap) on Day 1> Prednisone 40 mg/m^2/day PO on Days 1-5> filgrastim or pegfilgrastim as defined in the protocol> Required ancillary medications is administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Patients receive the following treatment:> Cycle 1 Doses:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to EPOCH chemotherapy> Doxorubicin 10 mg/m^2/day CIVI on Days 1-4> Etoposide 50 mg/m^2/day CIVI on Days 1-4> Vincristine 0.4 mg/m^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)> Cyclophosphamide 750 mg/m^2 IV on Day 5 (following completion of 96 hour infusions)> Prednisone 60 mg/m^2 PO BID on Days 1-5> Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC > 5000 after the > nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not > being monitored, during every cycle.> Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.> Required ancillary medications are administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Total of all reporting groups
Overall Participants 250 241 491
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
58.0
58.0
58.0
Sex: Female, Male (Count of Participants)
Female
116
46.4%
109
45.2%
225
45.8%
Male
133
53.2%
132
54.8%
265
54%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
16
6.4%
15
6.2%
31
6.3%
Not Hispanic or Latino
220
88%
214
88.8%
434
88.4%
Unknown or Not Reported
14
5.6%
12
5%
26
5.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
2
0.8%
2
0.8%
4
0.8%
Asian
9
3.6%
8
3.3%
17
3.5%
Native Hawaiian or Other Pacific Islander
1
0.4%
0
0%
1
0.2%
Black or African American
29
11.6%
31
12.9%
60
12.2%
White
196
78.4%
189
78.4%
385
78.4%
More than one race
2
0.8%
3
1.2%
5
1%
Unknown or Not Reported
11
4.4%
8
3.3%
19
3.9%
ECOG Performance Status (Count of Participants)
0
101
40.4%
113
46.9%
214
43.6%
1
119
47.6%
96
39.8%
215
43.8%
2
29
11.6%
32
13.3%
61
12.4%

Outcome Measures

1. Primary Outcome
Title Progression-Free Survival Rate at 2 and 5 Years
Description Progression-free survival (PFS) is defined as the time from randomization to progression, relapse, or death from any cause, whichever occurred first. Progression (PD) or Relapse> ≥ 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders.> Appearance of any new lesion during or after completion of therapy.> PET+ is not a criterion for progressive disease. Patients only with PET+ findings must have evidence of progression on CT or biopsy proven.> The PFS rate (percentage of participants who are alive and progression-free) at 2 and 5 years Kaplan Meier estimates and 95% Confidence Intervals are reported below.
Time Frame Up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Arm B - DA-EPOCH-R Arm A - R-CHOP
Arm/Group Description Patients receive the following treatment:> Cycle 1 Doses:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to EPOCH chemotherapy> Doxorubicin 10 mg/m^2/day CIVI on Days 1-4> Etoposide 50 mg/m^2/day CIVI on Days 1-4> Vincristine 0.4 mg/m^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)> Cyclophosphamide 750 mg/m^2 IV on Day 5 (following completion of 96 hour infusions)> Prednisone 60 mg/m^2 PO BID on Days 1-5> Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC > 5000 after the > nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not > being monitored, during every cycle.> Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.> Required ancillary medications are administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Patients receive the following treatment:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to CHOP chemotherapy> Cyclophosphamide 750 mg/m^2 IV on Day 1> Doxorubicin 50 mg/m^2 IV on Day 1> Vincristine 1.4 mg/m^2 IV (2 mg cap) on Day 1> Prednisone 40 mg/m^2/day PO on Days 1-5> filgrastim or pegfilgrastim as defined in the protocol> Required ancillary medications is administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.
Measure Participants 241 250
2-year PFS
78.9
31.6%
75.5
31.3%
5-year PFS
68.0
27.2%
66.0
27.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm B - DA-EPOCH-R, Arm A - R-CHOP
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6519
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.68 to 1.27
Parameter Dispersion Type:
Value:
Estimation Comments
2. Secondary Outcome
Title Response Rate
Description The overall response rate is defined as the percentage of participants with a response (Complete Response or Partial Response)
Time Frame Up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Arm B - DA-EPOCH-R Arm A - R-CHOP
Arm/Group Description Patients receive the following treatment:> Cycle 1 Doses:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to EPOCH chemotherapy> Doxorubicin 10 mg/m^2/day CIVI on Days 1-4> Etoposide 50 mg/m^2/day CIVI on Days 1-4> Vincristine 0.4 mg/m^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)> Cyclophosphamide 750 mg/m^2 IV on Day 5 (following completion of 96 hour infusions)> Prednisone 60 mg/m^2 PO BID on Days 1-5> Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC > 5000 after the > nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not > being monitored, during every cycle.> Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.> Required ancillary medications are administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Patients receive the following treatment:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to CHOP chemotherapy> Cyclophosphamide 750 mg/m^2 IV on Day 1> Doxorubicin 50 mg/m^2 IV on Day 1> Vincristine 1.4 mg/m^2 IV (2 mg cap) on Day 1> Prednisone 40 mg/m^2/day PO on Days 1-5> filgrastim or pegfilgrastim as defined in the protocol> Required ancillary medications is administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.
Measure Participants 241 250
Number [percentage of participants]
86.7
34.7%
88.0
36.5%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm B - DA-EPOCH-R, Arm A - R-CHOP
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.67
Comments
Method t-test, 2 sided
Comments
3. Secondary Outcome
Title Overall Survival Rate at 2 and 5 Years
Description Overall survival is defined as the time from randomization to death due to any cause. The overall survival (OS) rate (percentage of participants who are still alive) at 2 and 5 years Kaplan Meier estimates and 95% confidence intervals are reported below.
Time Frame Up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Arm B - DA-EPOCH-R Arm A - R-CHOP
Arm/Group Description Patients receive the following treatment:> Cycle 1 Doses:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to EPOCH chemotherapy> Doxorubicin 10 mg/m^2/day CIVI on Days 1-4> Etoposide 50 mg/m^2/day CIVI on Days 1-4> Vincristine 0.4 mg/m^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)> Cyclophosphamide 750 mg/m^2 IV on Day 5 (following completion of 96 hour infusions)> Prednisone 60 mg/m^2 PO BID on Days 1-5> Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC > 5000 after the > nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not > being monitored, during every cycle.> Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.> Required ancillary medications are administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6. Patients receive the following treatment:> Rituximab 375 mg/m^2 IV infusion on Day 1 prior to CHOP chemotherapy> Cyclophosphamide 750 mg/m^2 IV on Day 1> Doxorubicin 50 mg/m^2 IV on Day 1> Vincristine 1.4 mg/m^2 IV (2 mg cap) on Day 1> Prednisone 40 mg/m^2/day PO on Days 1-5> filgrastim or pegfilgrastim as defined in the protocol> Required ancillary medications is administered during all cycles as defined in the protocol.> Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.
Measure Participants 241 250
2-year OS rate
86.5
34.6%
85.7
35.6%
5-year OS rate
77.5
31%
78.5
32.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm B - DA-EPOCH-R, Arm A - R-CHOP
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.6414
Comments
Method Log Rank
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.75 to 1.59
Parameter Dispersion Type:
Value:
Estimation Comments
4. Other Pre-specified Outcome
Title Whether the Gene Expression Signatures That Were Previously Associated With Survival Following CHOP Therapy Are Associated With Survival in Either of the Treatment Arms of the Prospective Trial
Description
Time Frame Up to 5 years post-registration

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title
Arm/Group Description

Adverse Events

Time Frame Up to 5 years
Adverse Event Reporting Description All participants are followed for survival (i.e. included in the All-cause mortality table). Participants who received at least one dose of treatment are evaluable for adverse events (i.e. included in the Serious AE and Other (Not Including Serious) AE tables).
Arm/Group Title Arm A - R-CHOP Arm B - DA-EPOCH-R
Arm/Group Description Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6. Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.
All Cause Mortality
Arm A - R-CHOP Arm B - DA-EPOCH-R
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 53/250 (21.2%) 56/241 (23.2%)
Serious Adverse Events
Arm A - R-CHOP Arm B - DA-EPOCH-R
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 232/243 (95.5%) 214/237 (90.3%)
Blood and lymphatic system disorders
Febrile neutropenia 23/243 (9.5%) 26 43/237 (18.1%) 64
Hemoglobin decreased 193/243 (79.4%) 488 201/237 (84.8%) 564
Spleen disorder 1/243 (0.4%) 1 0/237 (0%) 0
Cardiac disorders
Atrial fibrillation 0/243 (0%) 0 2/237 (0.8%) 2
Cardiac disorder 0/243 (0%) 0 1/237 (0.4%) 1
Left ventricular failure 1/243 (0.4%) 1 0/237 (0%) 0
Myocardial ischemia 0/243 (0%) 0 1/237 (0.4%) 1
Palpitations 1/243 (0.4%) 1 0/237 (0%) 0
Sinus bradycardia 0/243 (0%) 0 2/237 (0.8%) 5
Sinus tachycardia 1/243 (0.4%) 2 2/237 (0.8%) 2
Ear and labyrinth disorders
Ear disorder 0/243 (0%) 0 1/237 (0.4%) 1
Hearing impaired 1/243 (0.4%) 1 0/237 (0%) 0
Eye disorders
Extraocular muscle paresis 1/243 (0.4%) 1 0/237 (0%) 0
Eye disorder 1/243 (0.4%) 1 0/237 (0%) 0
Photophobia 0/243 (0%) 0 1/237 (0.4%) 1
Vision blurred 2/243 (0.8%) 2 3/237 (1.3%) 4
Gastrointestinal disorders
Abdominal pain 8/243 (3.3%) 8 11/237 (4.6%) 17
Anal mucositis (clin exam) 0/243 (0%) 0 1/237 (0.4%) 1
Ascites 1/243 (0.4%) 2 0/237 (0%) 0
Colonic hemorrhage 0/243 (0%) 0 1/237 (0.4%) 2
Constipation 84/243 (34.6%) 128 81/237 (34.2%) 119
Diarrhea 13/243 (5.3%) 19 14/237 (5.9%) 14
Dry mouth 3/243 (1.2%) 3 1/237 (0.4%) 1
Dyspepsia 4/243 (1.6%) 4 4/237 (1.7%) 5
Esophageal mucositis (clin exam) 2/243 (0.8%) 2 0/237 (0%) 0
Esophageal pain 0/243 (0%) 0 1/237 (0.4%) 1
Gastritis 1/243 (0.4%) 2 3/237 (1.3%) 7
Gastrointestinal disorder 2/243 (0.8%) 2 0/237 (0%) 0
Hemorrhoids 1/243 (0.4%) 1 2/237 (0.8%) 2
Ileus 1/243 (0.4%) 1 2/237 (0.8%) 2
Mucositis oral (clin exam) 13/243 (5.3%) 18 23/237 (9.7%) 28
Mucositis oral (funct/sympt) 18/243 (7.4%) 31 32/237 (13.5%) 55
Nausea 21/243 (8.6%) 33 15/237 (6.3%) 25
Oral hemorrhage 1/243 (0.4%) 1 0/237 (0%) 0
Oral pain 0/243 (0%) 0 3/237 (1.3%) 3
Periodontal disease 0/243 (0%) 0 1/237 (0.4%) 1
Rectal hemorrhage 0/243 (0%) 0 3/237 (1.3%) 3
Rectal pain 1/243 (0.4%) 1 0/237 (0%) 0
Stomach pain 1/243 (0.4%) 1 1/237 (0.4%) 1
Tooth disorder 1/243 (0.4%) 1 1/237 (0.4%) 1
Toothache 1/243 (0.4%) 1 0/237 (0%) 0
Vomiting 8/243 (3.3%) 9 7/237 (3%) 9
General disorders
Chest pain 1/243 (0.4%) 1 2/237 (0.8%) 2
Chills 2/243 (0.8%) 2 3/237 (1.3%) 3
Death NOS 3/243 (1.2%) 3 1/237 (0.4%) 1
Disease progression 0/243 (0%) 0 1/237 (0.4%) 1
Edema limbs 7/243 (2.9%) 9 9/237 (3.8%) 12
Fatigue 27/243 (11.1%) 41 41/237 (17.3%) 60
Fever 6/243 (2.5%) 6 2/237 (0.8%) 2
Gait abnormal 0/243 (0%) 0 1/237 (0.4%) 1
General symptom 0/243 (0%) 0 1/237 (0.4%) 1
Localized edema 0/243 (0%) 0 1/237 (0.4%) 1
Multi-organ failure 0/243 (0%) 0 1/237 (0.4%) 1
Pain 2/243 (0.8%) 2 2/237 (0.8%) 2
Sudden death 0/243 (0%) 0 1/237 (0.4%) 1
Hepatobiliary disorders
Gallbladder pain 0/243 (0%) 0 1/237 (0.4%) 1
Immune system disorders
Hypersensitivity 15/243 (6.2%) 18 9/237 (3.8%) 9
Immune system disorder 0/243 (0%) 0 1/237 (0.4%) 1
Infections and infestations
Abdominal infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Anorectal infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Bladder infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Bladder infection(gr 3/4 ANC) 0/243 (0%) 0 2/237 (0.8%) 3
Bronchitis(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Bronchitis(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Catheter related infection 1/243 (0.4%) 1 0/237 (0%) 0
Catheter related infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Colitis, infectious 0/243 (0%) 0 1/237 (0.4%) 1
Device related infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Esophageal infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Esophageal infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Gingival infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Gingival infection(gr 3/4 ANC) 0/243 (0%) 0 3/237 (1.3%) 3
Infection(gr 0/1/2 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Infectious colitis(gr 3/4 ANC) 0/243 (0%) 0 2/237 (0.8%) 4
Nail infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Opportunistic infection 0/243 (0%) 0 1/237 (0.4%) 1
Otitis externa(gr 3/4 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Otitis media(gr 3/4 ANC) 2/243 (0.8%) 2 0/237 (0%) 0
Paranasal sinus infection(gr 0/1/2 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Pneumonia(gr 3/4 ANC) 0/243 (0%) 0 3/237 (1.3%) 4
Pneumonia(unknown ANC) 2/243 (0.8%) 2 1/237 (0.4%) 1
Rhinitis infective 0/243 (0%) 0 1/237 (0.4%) 1
Sepsis(gr 3/4 ANC) 1/243 (0.4%) 1 1/237 (0.4%) 1
Sepsis(unknown ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Sinusitis(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Sinusitis(gr 3/4 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Skin infection 1/243 (0.4%) 1 2/237 (0.8%) 2
Skin infection(gr 3/4 ANC) 2/243 (0.8%) 2 1/237 (0.4%) 1
Tooth infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Upper respiratory infection(gr 3/4 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Upper respiratory infectn(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Urinary tract infection(gr 0/1/2 ANC) 1/243 (0.4%) 1 1/237 (0.4%) 2
Urinary tract infection(gr 3/4 ANC) 1/243 (0.4%) 1 2/237 (0.8%) 3
Vaginal infection(gr 0/1/2 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Wound infection 0/243 (0%) 0 1/237 (0.4%) 1
Wound infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Injury, poisoning and procedural complications
Bruising 0/243 (0%) 0 1/237 (0.4%) 1
Fracture 1/243 (0.4%) 1 2/237 (0.8%) 2
Thermal burn 0/243 (0%) 0 1/237 (0.4%) 2
Vascular access complication 4/243 (1.6%) 4 4/237 (1.7%) 4
Wound dehiscence 0/243 (0%) 0 2/237 (0.8%) 2
Investigations
Activated partial throm time prolonged 1/243 (0.4%) 2 1/237 (0.4%) 2
Alanine aminotransferase increased 5/243 (2.1%) 6 7/237 (3%) 10
Alkaline phosphatase increased 0/243 (0%) 0 6/237 (2.5%) 18
Aspartate aminotransferase increased 8/243 (3.3%) 10 5/237 (2.1%) 6
Blood bilirubin increased 1/243 (0.4%) 1 4/237 (1.7%) 7
CD4 lymphocytes decreased 1/243 (0.4%) 4 2/237 (0.8%) 3
Creatinine increased 3/243 (1.2%) 6 5/237 (2.1%) 8
Gamma-glutamyltransferase increased 0/243 (0%) 0 4/237 (1.7%) 7
INR increased 0/243 (0%) 0 1/237 (0.4%) 2
Laboratory test abnormal 2/243 (0.8%) 3 2/237 (0.8%) 2
Leukocyte count decreased 72/243 (29.6%) 117 105/237 (44.3%) 242
Lymphocyte count decreased 60/243 (24.7%) 114 86/237 (36.3%) 231
Neutrophil count decreased 179/243 (73.7%) 331 190/237 (80.2%) 506
Platelet count decreased 97/243 (39.9%) 182 184/237 (77.6%) 479
Serum cholesterol increased 1/243 (0.4%) 3 0/237 (0%) 0
Weight loss 4/243 (1.6%) 5 1/237 (0.4%) 1
Metabolism and nutrition disorders
Anorexia 8/243 (3.3%) 9 14/237 (5.9%) 17
Blood glucose increased 20/243 (8.2%) 37 25/237 (10.5%) 39
Blood uric acid increased 1/243 (0.4%) 3 2/237 (0.8%) 2
Dehydration 22/243 (9.1%) 24 19/237 (8%) 22
Glucose intolerance 1/243 (0.4%) 1 0/237 (0%) 0
Serum albumin decreased 3/243 (1.2%) 4 12/237 (5.1%) 19
Serum calcium decreased 4/243 (1.6%) 4 15/237 (6.3%) 28
Serum calcium increased 1/243 (0.4%) 1 0/237 (0%) 0
Serum glucose decreased 0/243 (0%) 0 5/237 (2.1%) 10
Serum magnesium decreased 4/243 (1.6%) 4 4/237 (1.7%) 4
Serum magnesium increased 0/243 (0%) 0 5/237 (2.1%) 11
Serum phosphate decreased 5/243 (2.1%) 5 12/237 (5.1%) 14
Serum potassium decreased 5/243 (2.1%) 6 29/237 (12.2%) 44
Serum potassium increased 2/243 (0.8%) 3 1/237 (0.4%) 1
Serum sodium decreased 5/243 (2.1%) 5 6/237 (2.5%) 7
Serum sodium increased 0/243 (0%) 0 3/237 (1.3%) 5
Serum triglycerides increased 0/243 (0%) 0 1/237 (0.4%) 1
Tumor lysis syndrome 0/243 (0%) 0 1/237 (0.4%) 1
Musculoskeletal and connective tissue disorders
Arthralgia 5/243 (2.1%) 5 8/237 (3.4%) 9
Arthritis 1/243 (0.4%) 1 1/237 (0.4%) 1
Back pain 6/243 (2.5%) 7 5/237 (2.1%) 5
Bone pain 4/243 (1.6%) 5 17/237 (7.2%) 28
Chest wall pain 0/243 (0%) 0 3/237 (1.3%) 3
Muscle weakness 1/243 (0.4%) 2 5/237 (2.1%) 6
Muscle weakness lower limb 2/243 (0.8%) 2 2/237 (0.8%) 2
Musculoskeletal disorder 0/243 (0%) 0 1/237 (0.4%) 1
Myalgia 6/243 (2.5%) 8 3/237 (1.3%) 5
Myositis 1/243 (0.4%) 1 0/237 (0%) 0
Neck pain 1/243 (0.4%) 1 2/237 (0.8%) 2
Pain in extremity 6/243 (2.5%) 7 3/237 (1.3%) 4
Nervous system disorders
Arachnoiditis 0/243 (0%) 0 1/237 (0.4%) 1
Ataxia 1/243 (0.4%) 1 0/237 (0%) 0
Cognitive disturbance 0/243 (0%) 0 1/237 (0.4%) 1
Depressed level of consciousness 1/243 (0.4%) 1 0/237 (0%) 0
Dizziness 10/243 (4.1%) 11 8/237 (3.4%) 10
Dysgeusia 4/243 (1.6%) 6 4/237 (1.7%) 7
Encephalopathy 0/243 (0%) 0 1/237 (0.4%) 1
Extrapyramidal disorder 1/243 (0.4%) 2 0/237 (0%) 0
Headache 6/243 (2.5%) 8 14/237 (5.9%) 15
Intracranial hemorrhage 1/243 (0.4%) 1 0/237 (0%) 0
Neuralgia 0/243 (0%) 0 1/237 (0.4%) 1
Neurological disorder NOS 1/243 (0.4%) 1 0/237 (0%) 0
Peripheral motor neuropathy 23/243 (9.5%) 31 36/237 (15.2%) 62
Peripheral sensory neuropathy 104/243 (42.8%) 186 141/237 (59.5%) 322
Syncope 2/243 (0.8%) 2 2/237 (0.8%) 2
Tremor 2/243 (0.8%) 2 1/237 (0.4%) 1
Psychiatric disorders
Agitation 1/243 (0.4%) 1 0/237 (0%) 0
Anxiety 2/243 (0.8%) 4 5/237 (2.1%) 7
Confusion 1/243 (0.4%) 1 0/237 (0%) 0
Depression 5/243 (2.1%) 8 7/237 (3%) 9
Insomnia 8/243 (3.3%) 11 5/237 (2.1%) 6
Libido decreased 0/243 (0%) 0 1/237 (0.4%) 2
Psychosis 0/243 (0%) 0 1/237 (0.4%) 1
Renal and urinary disorders
Cystitis 1/243 (0.4%) 1 1/237 (0.4%) 1
Kidney pain 0/243 (0%) 0 1/237 (0.4%) 1
Renal failure 0/243 (0%) 0 1/237 (0.4%) 1
Urinary frequency 2/243 (0.8%) 2 1/237 (0.4%) 1
Urinary retention 0/243 (0%) 0 2/237 (0.8%) 2
Reproductive system and breast disorders
Erectile dysfunction 1/243 (0.4%) 1 1/237 (0.4%) 2
Gynecomastia 0/243 (0%) 0 1/237 (0.4%) 1
Pelvic pain 1/243 (0.4%) 2 0/237 (0%) 0
Testicular hemorrhage 1/243 (0.4%) 1 0/237 (0%) 0
Vaginal hemorrhage 0/243 (0%) 0 1/237 (0.4%) 1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis 3/243 (1.2%) 3 4/237 (1.7%) 6
Cough 6/243 (2.5%) 7 9/237 (3.8%) 12
Dyspnea 4/243 (1.6%) 4 11/237 (4.6%) 17
Nasal congestion 0/243 (0%) 0 1/237 (0.4%) 1
Pharyngeal mucositis (funct/sympt) 0/243 (0%) 0 1/237 (0.4%) 2
Pharyngeal stenosis 0/243 (0%) 0 1/237 (0.4%) 1
Pharyngolaryngeal pain 3/243 (1.2%) 3 1/237 (0.4%) 2
Pleural effusion 0/243 (0%) 0 1/237 (0.4%) 1
Pneumonitis 2/243 (0.8%) 3 0/237 (0%) 0
Respiratory disorder 0/243 (0%) 0 1/237 (0.4%) 1
Voice alteration 0/243 (0%) 0 2/237 (0.8%) 2
Skin and subcutaneous tissue disorders
Alopecia 13/243 (5.3%) 23 8/237 (3.4%) 19
Body odor 1/243 (0.4%) 1 0/237 (0%) 0
Decubitus ulcer 0/243 (0%) 0 1/237 (0.4%) 1
Dry skin 0/243 (0%) 0 2/237 (0.8%) 2
Hand-and-foot syndrome/reaction 0/243 (0%) 0 1/237 (0.4%) 1
Nail disorder 0/243 (0%) 0 4/237 (1.7%) 4
Pruritus 1/243 (0.4%) 1 2/237 (0.8%) 2
Rash desquamating 3/243 (1.2%) 3 4/237 (1.7%) 4
Skin disorder 2/243 (0.8%) 2 1/237 (0.4%) 2
Skin hyperpigmentation 1/243 (0.4%) 1 2/237 (0.8%) 4
Skin ulceration 1/243 (0.4%) 1 1/237 (0.4%) 1
Sweating 6/243 (2.5%) 8 0/237 (0%) 0
Vascular disorders
Flushing 0/243 (0%) 0 2/237 (0.8%) 2
Hemorrhage 0/243 (0%) 0 1/237 (0.4%) 1
Hot flashes 1/243 (0.4%) 2 0/237 (0%) 0
Hypertension 2/243 (0.8%) 4 9/237 (3.8%) 12
Hypotension 0/243 (0%) 0 7/237 (3%) 11
Thrombosis 6/243 (2.5%) 6 4/237 (1.7%) 5
Vascular disorder 2/243 (0.8%) 2 0/237 (0%) 0
Other (Not Including Serious) Adverse Events
Arm A - R-CHOP Arm B - DA-EPOCH-R
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 94/243 (38.7%) 119/237 (50.2%)
Blood and lymphatic system disorders
Blood disorder 1/243 (0.4%) 1 0/237 (0%) 0
Febrile neutropenia 26/243 (10.7%) 27 44/237 (18.6%) 57
Hemoglobin decreased 80/243 (32.9%) 126 116/237 (48.9%) 199
Lymphatic disorder 1/243 (0.4%) 1 1/237 (0.4%) 1
Cardiac disorders
Asystole 0/243 (0%) 0 1/237 (0.4%) 1
Atrial fibrillation 4/243 (1.6%) 5 6/237 (2.5%) 7
Atrial flutter 1/243 (0.4%) 1 0/237 (0%) 0
Atrial tachycardia 0/243 (0%) 0 1/237 (0.4%) 1
Cardiac disorder 0/243 (0%) 0 1/237 (0.4%) 1
Cardiopulmonary arrest 1/243 (0.4%) 1 1/237 (0.4%) 1
Left ventricular dysfunction 2/243 (0.8%) 2 0/237 (0%) 0
Left ventricular failure 6/243 (2.5%) 6 3/237 (1.3%) 3
Myocardial ischemia 2/243 (0.8%) 2 0/237 (0%) 0
Sinus bradycardia 0/243 (0%) 0 1/237 (0.4%) 1
Sinus tachycardia 1/243 (0.4%) 1 7/237 (3%) 7
Ear and labyrinth disorders
Ear pain 1/243 (0.4%) 1 0/237 (0%) 0
Hearing impaired 1/243 (0.4%) 1 0/237 (0%) 0
Endocrine disorders
Adrenal insufficiency 0/243 (0%) 0 1/237 (0.4%) 1
Gastrointestinal disorders
Abdominal pain 10/243 (4.1%) 11 8/237 (3.4%) 9
Ascites 2/243 (0.8%) 2 1/237 (0.4%) 1
Colitis 1/243 (0.4%) 2 1/237 (0.4%) 1
Colonic hemorrhage 0/243 (0%) 0 1/237 (0.4%) 2
Constipation 18/243 (7.4%) 20 35/237 (14.8%) 45
Diarrhea 8/243 (3.3%) 9 14/237 (5.9%) 15
Duodenal hemorrhage 0/243 (0%) 0 1/237 (0.4%) 1
Duodenal stenosis 1/243 (0.4%) 1 0/237 (0%) 0
Dyspepsia 2/243 (0.8%) 2 1/237 (0.4%) 1
Dysphagia 1/243 (0.4%) 1 7/237 (3%) 7
Esophagitis 0/243 (0%) 0 2/237 (0.8%) 3
Fecal incontinence 0/243 (0%) 0 1/237 (0.4%) 1
Gastric hemorrhage 1/243 (0.4%) 1 2/237 (0.8%) 2
Gastric perforation 1/243 (0.4%) 1 0/237 (0%) 0
Gastritis 1/243 (0.4%) 1 1/237 (0.4%) 1
Ileal perforation 0/243 (0%) 0 1/237 (0.4%) 1
Ileus 4/243 (1.6%) 4 5/237 (2.1%) 6
Jejunal obstruction 0/243 (0%) 0 1/237 (0.4%) 1
Lower gastrointestinal hemorrhage 1/243 (0.4%) 1 0/237 (0%) 0
Malabsorption 0/243 (0%) 0 1/237 (0.4%) 1
Mucositis oral (clin exam) 3/243 (1.2%) 4 13/237 (5.5%) 19
Mucositis oral (funct/sympt) 5/243 (2.1%) 5 17/237 (7.2%) 21
Nausea 9/243 (3.7%) 9 13/237 (5.5%) 15
Oral pain 0/243 (0%) 0 3/237 (1.3%) 3
Periodontal disease 0/243 (0%) 0 1/237 (0.4%) 1
Small intestinal obstruction 1/243 (0.4%) 1 1/237 (0.4%) 1
Small intestinal perforation 1/243 (0.4%) 1 0/237 (0%) 0
Small intestinal stenosis 0/243 (0%) 0 1/237 (0.4%) 1
Upper gastrointestinal hemorrhage 1/243 (0.4%) 1 0/237 (0%) 0
Vomiting 6/243 (2.5%) 6 11/237 (4.6%) 12
General disorders
Chest pain 1/243 (0.4%) 1 4/237 (1.7%) 4
Chills 1/243 (0.4%) 1 0/237 (0%) 0
Edema limbs 10/243 (4.1%) 11 6/237 (2.5%) 6
Fatigue 14/243 (5.8%) 17 20/237 (8.4%) 23
Fever 3/243 (1.2%) 3 2/237 (0.8%) 2
Hypothermia 0/243 (0%) 0 1/237 (0.4%) 1
Ill-defined disorder 1/243 (0.4%) 1 1/237 (0.4%) 1
Pain 0/243 (0%) 0 3/237 (1.3%) 3
Visceral edema 0/243 (0%) 0 1/237 (0.4%) 1
Hepatobiliary disorders
Gallbladder obstruction 0/243 (0%) 0 1/237 (0.4%) 1
Gallbladder pain 0/243 (0%) 0 1/237 (0.4%) 1
Immune system disorders
Cytokine release syndrome 0/243 (0%) 0 1/237 (0.4%) 1
Hypersensitivity 2/243 (0.8%) 2 5/237 (2.1%) 5
Immune system disorder 0/243 (0%) 0 1/237 (0.4%) 1
Infections and infestations
Abdominal infection 0/243 (0%) 0 1/237 (0.4%) 1
Abdominal infection(unknown ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Anorectal infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Appendicitis perforated 0/243 (0%) 0 1/237 (0.4%) 1
Bladder infection(gr 0/1/2 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Bladder infection(gr 3/4 ANC) 0/243 (0%) 0 2/237 (0.8%) 2
Bronchitis(gr 3/4 ANC) 1/243 (0.4%) 1 1/237 (0.4%) 1
Catheter related infection 1/243 (0.4%) 1 0/237 (0%) 0
Catheter related infection(gr 0/1/2 ANC) 2/243 (0.8%) 2 1/237 (0.4%) 1
Catheter related infection(gr 3/4 ANC) 4/243 (1.6%) 4 4/237 (1.7%) 4
Colitis, infectious 1/243 (0.4%) 1 2/237 (0.8%) 3
Esophageal infection(unknown ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Gingival infection(gr 3/4 ANC) 0/243 (0%) 0 2/237 (0.8%) 2
Infection(gr 0/1/2 ANC) 2/243 (0.8%) 3 6/237 (2.5%) 6
Infectious colitis(gr 0/1/2 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Infectious colitis(gr 3/4 ANC) 0/243 (0%) 0 2/237 (0.8%) 3
Lip infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Lymph gland infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Mucosal infection(gr 3/4 ANC) 0/243 (0%) 0 2/237 (0.8%) 2
Opportunistic infection 1/243 (0.4%) 1 0/237 (0%) 0
Pancreas infection(gr 3/4 ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Peritoneal infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Pneumonia(gr 0/1/2 ANC) 3/243 (1.2%) 3 0/237 (0%) 0
Pneumonia(gr 3/4 ANC) 4/243 (1.6%) 4 5/237 (2.1%) 5
Pneumonia(unknown ANC) 1/243 (0.4%) 1 0/237 (0%) 0
Sepsis(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Sepsis(gr 3/4 ANC) 2/243 (0.8%) 2 3/237 (1.3%) 4
Sepsis(unknown ANC) 0/243 (0%) 0 3/237 (1.3%) 3
Skin infection 1/243 (0.4%) 1 1/237 (0.4%) 1
Skin infection(gr 3/4 ANC) 2/243 (0.8%) 2 1/237 (0.4%) 1
Tooth infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Upper respiratory infection(gr 3/4 ANC) 3/243 (1.2%) 3 0/237 (0%) 0
Upper respiratory infectn(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Urinary tract infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Urinary tract infection(gr 3/4 ANC) 3/243 (1.2%) 3 5/237 (2.1%) 6
Vaginal infection(gr 0/1/2 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Vaginal infection(gr 3/4 ANC) 0/243 (0%) 0 1/237 (0.4%) 1
Wound infection 0/243 (0%) 0 2/237 (0.8%) 2
Wound infection(gr 0/1/2 ANC) 1/243 (0.4%) 1 1/237 (0.4%) 1
Wound infection(gr 3/4 ANC) 2/243 (0.8%) 2 1/237 (0.4%) 1
Injury, poisoning and procedural complications
Bruising 0/243 (0%) 0 2/237 (0.8%) 2
Fracture 1/243 (0.4%) 1 0/237 (0%) 0
Intraop. inj. - Spinal cord 0/243 (0%) 0 1/237 (0.4%) 1
Thermal burn 0/243 (0%) 0 1/237 (0.4%) 1
Vascular access complication 1/243 (0.4%) 1 3/237 (1.3%) 4
Venous injury - Viscera 0/243 (0%) 0 1/237 (0.4%) 1
Wound dehiscence 0/243 (0%) 0 1/237 (0.4%) 1
Investigations
Activated partial throm time prolonged 0/243 (0%) 0 4/237 (1.7%) 4
Alanine aminotransferase increased 3/243 (1.2%) 3 6/237 (2.5%) 6
Alkaline phosphatase increased 2/243 (0.8%) 2 5/237 (2.1%) 5
Aspartate aminotransferase increased 3/243 (1.2%) 3 4/237 (1.7%) 4
Blood bilirubin increased 4/243 (1.6%) 4 4/237 (1.7%) 5
CD4 lymphocytes decreased 1/243 (0.4%) 1 2/237 (0.8%) 3
Cardiac troponin T increased 0/243 (0%) 0 1/237 (0.4%) 1
Creatine phosphokinase increased 1/243 (0.4%) 1 0/237 (0%) 0
Creatinine increased 1/243 (0.4%) 2 3/237 (1.3%) 3
Leukocyte count decreased 42/243 (17.3%) 58 66/237 (27.8%) 106
Lipase increased 1/243 (0.4%) 1 0/237 (0%) 0
Lymphocyte count decreased 34/243 (14%) 52 51/237 (21.5%) 93
Neutrophil count decreased 74/243 (30.5%) 109 107/237 (45.1%) 169
Platelet count decreased 53/243 (21.8%) 73 107/237 (45.1%) 167
Serum cholesterol increased 1/243 (0.4%) 1 4/237 (1.7%) 6
Weight loss 4/243 (1.6%) 4 4/237 (1.7%) 4
Metabolism and nutrition disorders
Acidosis 1/243 (0.4%) 1 1/237 (0.4%) 1
Alkalosis 1/243 (0.4%) 1 0/237 (0%) 0
Anorexia 7/243 (2.9%) 7 5/237 (2.1%) 6
Blood glucose increased 12/243 (4.9%) 13 13/237 (5.5%) 18
Blood uric acid increased 2/243 (0.8%) 2 3/237 (1.3%) 5
Dehydration 16/243 (6.6%) 18 21/237 (8.9%) 28
Serum albumin decreased 8/243 (3.3%) 10 19/237 (8%) 23
Serum calcium decreased 7/243 (2.9%) 8 16/237 (6.8%) 20
Serum calcium increased 1/243 (0.4%) 1 0/237 (0%) 0
Serum glucose decreased 1/243 (0.4%) 1 3/237 (1.3%) 3
Serum magnesium decreased 1/243 (0.4%) 1 4/237 (1.7%) 4
Serum magnesium increased 1/243 (0.4%) 1 4/237 (1.7%) 4
Serum phosphate decreased 5/243 (2.1%) 6 11/237 (4.6%) 14
Serum potassium decreased 5/243 (2.1%) 5 23/237 (9.7%) 28
Serum potassium increased 2/243 (0.8%) 2 2/237 (0.8%) 2
Serum sodium decreased 8/243 (3.3%) 8 10/237 (4.2%) 13
Serum sodium increased 0/243 (0%) 0 1/237 (0.4%) 1
Serum triglycerides increased 0/243 (0%) 0 1/237 (0.4%) 2
Tumor lysis syndrome 2/243 (0.8%) 2 1/237 (0.4%) 1
Musculoskeletal and connective tissue disorders
Arthralgia 1/243 (0.4%) 1 0/237 (0%) 0
Back pain 3/243 (1.2%) 3 2/237 (0.8%) 2
Bone pain 1/243 (0.4%) 1 5/237 (2.1%) 5
Muscle weakness 3/243 (1.2%) 3 8/237 (3.4%) 10
Muscle weakness lower limb 1/243 (0.4%) 1 1/237 (0.4%) 1
Muscle weakness right-sided 1/243 (0.4%) 1 0/237 (0%) 0
Musculoskeletal disorder 0/243 (0%) 0 1/237 (0.4%) 1
Myalgia 0/243 (0%) 0 1/237 (0.4%) 1
Neck pain 0/243 (0%) 0 2/237 (0.8%) 2
Neck soft tissue necrosis 0/243 (0%) 0 1/237 (0.4%) 2
Pain in extremity 1/243 (0.4%) 1 3/237 (1.3%) 3
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain 1/243 (0.4%) 1 1/237 (0.4%) 1
Nervous system disorders
Cognitive disturbance 1/243 (0.4%) 1 0/237 (0%) 0
Depressed level of consciousness 1/243 (0.4%) 1 1/237 (0.4%) 1
Dizziness 5/243 (2.1%) 6 2/237 (0.8%) 2
Dysgeusia 2/243 (0.8%) 2 1/237 (0.4%) 1
Encephalopathy 0/243 (0%) 0 1/237 (0.4%) 1
Headache 2/243 (0.8%) 2 2/237 (0.8%) 2
Ischemia cerebrovascular 0/243 (0%) 0 1/237 (0.4%) 1
Mini mental status examination abnormal 0/243 (0%) 0 1/237 (0.4%) 1
Neurological disorder NOS 0/243 (0%) 0 1/237 (0.4%) 1
Peripheral motor neuropathy 5/243 (2.1%) 5 16/237 (6.8%) 20
Peripheral sensory neuropathy 25/243 (10.3%) 31 68/237 (28.7%) 108
Seizure 0/243 (0%) 0 3/237 (1.3%) 3
Syncope 0/243 (0%) 0 3/237 (1.3%) 3
Psychiatric disorders
Anxiety 0/243 (0%) 0 3/237 (1.3%) 3
Confusion 0/243 (0%) 0 1/237 (0.4%) 1
Depression 0/243 (0%) 0 4/237 (1.7%) 4
Insomnia 3/243 (1.2%) 3 4/237 (1.7%) 4
Renal and urinary disorders
Bladder pain 0/243 (0%) 0 1/237 (0.4%) 1
Bladder spasm 0/243 (0%) 0 1/237 (0.4%) 1
Cystitis 1/243 (0.4%) 1 1/237 (0.4%) 1
Hemorrhage urinary tract 1/243 (0.4%) 1 0/237 (0%) 0
Kidney pain 0/243 (0%) 0 1/237 (0.4%) 1
Proteinuria 0/243 (0%) 0 1/237 (0.4%) 1
Renal failure 4/243 (1.6%) 4 5/237 (2.1%) 5
Urinary frequency 1/243 (0.4%) 1 0/237 (0%) 0
Urinary retention 1/243 (0.4%) 1 0/237 (0%) 0
Urogenital disorder 1/243 (0.4%) 1 0/237 (0%) 0
Reproductive system and breast disorders
Pelvic pain 1/243 (0.4%) 1 0/237 (0%) 0
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome 2/243 (0.8%) 2 0/237 (0%) 0
Allergic rhinitis 0/243 (0%) 0 1/237 (0.4%) 1
Atelectasis 0/243 (0%) 0 1/237 (0.4%) 1
Cough 2/243 (0.8%) 2 4/237 (1.7%) 4
Dyspnea 8/243 (3.3%) 10 9/237 (3.8%) 10
Hiccups 0/243 (0%) 0 1/237 (0.4%) 1
Hypoxia 4/243 (1.6%) 4 8/237 (3.4%) 9
Pharyngeal mucositis (clin exam) 0/243 (0%) 0 1/237 (0.4%) 1
Pharyngolaryngeal pain 1/243 (0.4%) 1 2/237 (0.8%) 2
Pleural effusion 2/243 (0.8%) 2 2/237 (0.8%) 2
Pneumonitis 4/243 (1.6%) 4 3/237 (1.3%) 3
Pneumothorax 1/243 (0.4%) 1 0/237 (0%) 0
Respiratory disorder 0/243 (0%) 0 1/237 (0.4%) 1
Voice alteration 0/243 (0%) 0 1/237 (0.4%) 1
Skin and subcutaneous tissue disorders
Alopecia 4/243 (1.6%) 4 6/237 (2.5%) 6
Decubitus ulcer 1/243 (0.4%) 1 1/237 (0.4%) 1
Erythema multiforme 0/243 (0%) 0 1/237 (0.4%) 1
Nail disorder 0/243 (0%) 0 1/237 (0.4%) 1
Pruritus 0/243 (0%) 0 2/237 (0.8%) 2
Rash acneiform 0/243 (0%) 0 1/237 (0.4%) 1
Rash desquamating 1/243 (0.4%) 1 1/237 (0.4%) 1
Skin ulceration 2/243 (0.8%) 2 0/237 (0%) 0
Sweating 1/243 (0.4%) 1 1/237 (0.4%) 1
Vascular disorders
Flushing 0/243 (0%) 0 1/237 (0.4%) 1
Hemorrhage 0/243 (0%) 0 1/237 (0.4%) 1
Hypertension 1/243 (0.4%) 1 2/237 (0.8%) 2
Hypotension 8/243 (3.3%) 8 13/237 (5.5%) 15
Thrombosis 6/243 (2.5%) 6 10/237 (4.2%) 11
Vascular disorder 1/243 (0.4%) 1 1/237 (0.4%) 1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS 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.

Results Point of Contact

Name/Title Nancy Bartlett, M.D.
Organization Washington University School of Medicine
Phone 314-362-5654
Email nbartlet@wustl.edu
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00118209
Other Study ID Numbers:
  • CALGB-50303
  • CDR0000433265
  • NCI-2009-00480
  • U10CA031946
  • U10CA180821
  • NCT00234351
First Posted:
Jul 11, 2005
Last Update Posted:
Nov 17, 2021
Last Verified:
Nov 1, 2021