Rituximab and Combination Chemotherapy in Treating Patients With Stage II, Stage III, or Stage IV Diffuse Large B-Cell Non-Hodgkin's Lymphoma

• Sponsor: Eastern Cooperative Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00274924
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 100
• Locations: 104
• Arms: 2
• Actual Duration (Months): 155
• Patients Per Site: 1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving rituximab together with combination chemotherapy works in treating patients with stage II, stage III, or stage IV diffuse large B-cell non-Hodgkin's lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim; Biological: rituximab; Drug: carboplatin; Drug: cyclophosphamide; Drug: doxorubicin hydrochloride; Drug: etoposide; Drug: ifosfamide; Drug: prednisone; Drug: vincristine	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the 2-year progression-free survival (PFS) rate after treatment with rituximab, ifosfamide, carboplatin, and etoposide (R-ICE) in patients with bulky stage II or stage III or IV diffuse large B-cell non-Hodgkin's lymphoma who remain positron emission tomography (PET)-positive after 3 courses of rituximab, cyclophosphamide, vincristine, doxorubicin hydrochloride, and prednisone.

Secondary

• Determine the proportion of mid-treatment PET-positive patients who become PET-negative after 4 courses of R-ICE.

• Determine the PFS of mid-treatment PET-negative patients treated with these regimens.

• Determine the overall survival of patients treated with these regimens.

• Determine the toxicity of these regimens in these patients.

OUTLINE:

• Rituximab and Combination Chemotherapy (R-CHOP: R= Rituximab, C= Cyclophosphamide, H= Doxorubicin Hydrochloride (Hydroxydaunomycin), O= Vincristine Sulfate (Oncovin), P= Prednisone): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients undergo fludeoxyglucose F18 positron emission tomography (PET) scanning and conventional restaging during course 3. Based on the PET results, patients are assigned to 1 of 2 treatment groups.

• Group I (PET negative): Patients receive 2 more courses of R-CHOP as above in the absence of disease progression or unacceptable toxicity.

• Group II (PET positive): Patients receive Rituximab 375 mg/m2 IV Day 1, Ifosfamide 5000 mg/m2 IV over 24 hours Day 2, Carboplatin AUC 5 (max: 800 mg) IV Day 2, Etoposide 100 mg/m2 IV Days 1, 2, 3 (R-ICE), Mesna 5000 mg/m2 IV over 24 hours Day 2, and Filgrastim 5 mcg/kg/day subcutaneous (SC) Day 4 until absolute neutrophil count (ANC) recovery every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 10 years from the date of study entry.

ACCRUAL: A total of 100 patients were accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 100 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Response-Adapted Therapy for Aggressive Non-Hodgkin's Lymphomas Based on Early [18F] FDG-PET Scanning
• Actual Study Start Date: Apr 1, 2006
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Mar 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group I (PET negative) Patients receive rituximab IV, cyclophosphamide IV, doxorubicin hydrochloride IV, and vincristine IV on day 1, and oral prednisone once daily on days 1-5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.	Biological: rituximab; Given IV; Other Names: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan. ; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan, Neosar, CTX, CPM. ; Drug: doxorubicin hydrochloride; Given IV; Other Names: Adriamycin, Rubex, Adriamycin RDF, Adriamycin PFS, hydroxydaunorubicin, hydroxydaunomycin, ADR. ; Drug: prednisone; Taken orally; Other Names: Deltasone, Orasone, Medicorten, Panasol-S, Liquid-Pred, others. ; Drug: vincristine; Given IV; Other Names: Oncovin, Vincasar PFS vincristine sulfate, VCR, leucocristine, LCR.
Experimental: Group II (PET positive) Patients receive R-ICE comprising rituximab IV on day 1, ifosfamide IV continuously over 24 hours and carboplatin IV over 30 minutes on day 2, and etoposide IV over 2 hours on days 1-3. Patients also receive filgrastim (G-CSF) subcutaneously once daily starting on day 4 and continuing until blood counts recover. Treatment repeats every 14 days for 4 courses in the absence of disease progression or unacceptable toxicity.	Biological: filgrastim; Given subcutaneously or intravenous bolus.; Other Names: G-CSF, Neupogen, recombinant-methionyl human granulocyte-colony stimulating factor, granulocyte colony-stimulating factor, r-metHuG-CSF. ; Biological: rituximab; Given IV; Other Names: IDEC-C2B8, Chimeric anti-CD20 monoclonal antibody, Rituxan. ; Drug: carboplatin; Given IV; Other Names: CBDCA, Paraplatin, JM-8, NSC #241240. ; Drug: cyclophosphamide; Given IV; Other Names: Cytoxan, Neosar, CTX, CPM. ; Drug: etoposide; Given IV; Other Names: VP-16, VePesid, epipodophyllotoxin ; Drug: ifosfamide; Given IV; Other Names: Isophosphamide, Ifex , Mitoxan , Holoxan , Naxamide ' NSC # 109724.

Outcome Measures

Primary Outcome Measures

1. 2-year Progression-Free Survival (PFS) [Assessed every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.]

   2-year progression-free survival is defined as the probability of patients who remain alive and progression free at 2 years from study entry. The method of Kaplan and Meier (1958) was used to estimate PFS.

Secondary Outcome Measures

1. 5-year Overall Survival [Every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.]

   5-year overall survival is defined as the probability of patients who remain alive at 5 years from study entry. The method of Kaplan and Meier (1958) was used to estimate overall survival.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA:

• Diffuse large B-cell non-Hodgkin's lymphoma

• Bulky stage II (bulk defined as any lesion ≥ 10 cm) or stage III or IV disease

• The following lymphoma types are excluded:

• Primary central nervous system lymphoma

• Transformed low-grade lymphoma (prior history of low-grade lymphoma or clear presence of low-grade lymphoma on histologic sections)

• Primary mediastinal B-cell lymphoma or testicular lymphoma (consolidative radiotherapy is usually indicated)

• Immunodeficiency-related lymphoma (i.e., after organ or bone marrow transplant)

• Measurable disease

• Patient must have at least one objective measurable disease site (i.e., measurable in at least 2 perpendicular parameters)

• Measurable disease in the liver is required if the liver is the only site of lymphoma involvement

• Abnormal positron emission tomography scans will not constitute evaluable disease, unless verified by CT scan or other appropriate imaging

• Eastern Cooperative Oncology Group (ECOG) performance status 0-3

• For patients > 50 years of age, a normal ejection fraction by ECHO or Multigated Acquisition Scan (MUGA) is required within 6 weeks prior to registration

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count > 100,000/mm^3

• Creatinine < 2.0 mg/dL

• Bilirubin < 2 mg/dL (may be up to 3.0 mg/dL if due to liver involvement by lymphoma)

EXCLUSION CRITERIA:

• Prior chemotherapy or radiation therapy for lymphoma

• Prior anthracyclines or platinum compounds used as systemic chemotherapy

• Prior radiation therapy to the mediastinum or to ≥ 25% of the bone marrow

• Concurrent pentostatin or trastuzumab (Herceptin®)

• Pregnant or nursing

• Prior malignancy within the past 5 years unless it was in situ OR was treated with curative intent AND the patient has remained relapse-free

• HIV positive

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
2	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
3	Baptist Cancer Institute - Jacksonville	Jacksonville	Florida	United States	32207
4	Mayo Clinic - Jacksonville	Jacksonville	Florida	United States	32224
5	Rush-Copley Cancer Care Center	Aurora	Illinois	United States	60504
6	St. Joseph Medical Center	Bloomington	Illinois	United States	61701
7	Graham Hospital	Canton	Illinois	United States	61520
8	Memorial Hospital	Carthage	Illinois	United States	62321
9	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois	United States	60611-3013
10	Eureka Community Hospital	Eureka	Illinois	United States	61530
11	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois	United States	60201-1781
12	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
13	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
14	Mason District Hospital	Havana	Illinois	United States	62644
15	Hinsdale Hematology Oncology Associates	Hinsdale	Illinois	United States	60521
16	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
17	Joliet Oncology-Hematology Associates, Limited - West	Joliet	Illinois	United States	60435
18	McDonough District Hospital	Macomb	Illinois	United States	61455
19	Trinity Cancer Center at Trinity Medical Center - 7th Street Campus	Moline	Illinois	United States	61265
20		Moline	Illinois	United States	61265
21	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
22	Community Cancer Center	Normal	Illinois	United States	61761
23	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
24	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
25	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
26	Proctor Hospital	Peoria	Illinois	United States	61614
27	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
28	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
29	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
30	OSF St. Francis Medical Center	Peoria	Illinois	United States	61637
31	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
32	Perry Memorial Hospital	Princeton	Illinois	United States	61356
33	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
34	Carle Cancer Center at Carle Foundation Hospital	Urbana	Illinois	United States	61801
35	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
36	Saint Anthony Memorial Health Centers	Michigan City	Indiana	United States	46360
37	McFarland Clinic, PC	Ames	Iowa	United States	50010
38		Bettendorf	Iowa	United States	52722
39	Mercy Capitol Hospital	Des Moines	Iowa	United States	50307
40	CCOP - Iowa Oncology Research Association	Des Moines	Iowa	United States	50309
41	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
42	Medical Oncology and Hematology Associates at John Stoddard Cancer Center	Des Moines	Iowa	United States	50309
43	Medical Oncology and Hematology Associates at Mercy Cancer Center	Des Moines	Iowa	United States	50314
44	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
45	John Stoddard Cancer Center at Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
46	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa	United States	51101
47	Mercy Medical Center - Sioux City	Sioux City	Iowa	United States	51104
48	St. Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
49	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland	United States	21204
50	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
51	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan	United States	48106-0995
52	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan	United States	48106
53	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan	United States	48123-2500
54	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
55	Hurley Medical Center	Flint	Michigan	United States	48503
56	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan	United States	48236
57	Foote Memorial Hospital	Jackson	Michigan	United States	49201
58	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
59	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
60	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
61	Sparrow Regional Cancer Center	Lansing	Michigan	United States	48912-1811
62	St. Mary Mercy Hospital	Livonia	Michigan	United States	48154
63	St. Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
64	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan	United States	48060
65	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan	United States	48601
66	St. John Macomb Hospital	Warren	Michigan	United States	48093
67	Duluth Clinic Cancer Center - Duluth	Duluth	Minnesota	United States	55805-1983
68	CCOP - Duluth	Duluth	Minnesota	United States	55805
69	Miller - Dwan Medical Center	Duluth	Minnesota	United States	55805
70	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
71	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
72	SUNY Downstate Medical Center	Brooklyn	New York	United States	11203
73	NYU Cancer Institute at New York University Medical Center	New York	New York	United States	10016
74	Aultman Cancer Center at Aultman Hospital	Canton	Ohio	United States	44710-1799
75	Christ Hospital Cancer Center	Cincinnati	Ohio	United States	45219
76	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio	United States	44109
77	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
78	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania	United States	17822-0001
79	Penn State Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
80	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
81	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
82	Geisinger Medical Group - Scenery Park	State College	Pennsylvania	United States	16801
83	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
84	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania	United States	18711
85	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
86	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
87	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
88	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
89	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
90	Center for Cancer Treatment & Prevention at Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
91	Marshfield Clinic Cancer Care at Regional Cancer Center	Eau Claire	Wisconsin	United States	54701
92	Gundersen Lutheran Center for Cancer and Blood	La Crosse	Wisconsin	United States	54601
93	Dean Medical Center - Madison	Madison	Wisconsin	United States	53717
94	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449
95	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
96	Froedtert Hospital and Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
97	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin	United States	53226
98	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin	United States	54548
99	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin	United States	54501
100	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin	United States	54868
101	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin	United States	54481
102	Marshfield Clinic - Wausau Center	Wausau	Wisconsin	United States	54401
103	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
104	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494

Sponsors and Collaborators

• Eastern Cooperative Oncology Group
• National Cancer Institute (NCI)

Investigators

• Study Chair: Lode J. Swinnen, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eastern Cooperative Oncology Group
• ClinicalTrials.gov Identifier: NCT00274924
• Other Study ID Numbers: CDR0000455012; U10CA021115; E3404
• First Posted: Jan 11, 2006
• Last Update Posted: Nov 17, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by Eastern Cooperative Oncology Group: contiguous stage II adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Prednisone; Cyclophosphamide; Ifosfamide; Rituximab; Carboplatin; Doxorubicin; Liposomal doxorubicin; Etoposide; Vincristine; Podophyllotoxin; Lenograstim

Study Results

Participant Flow

Recruitment Details	Participants were recruited from Eastern Cooperative Oncology Group (ECOG) member institutions between 4/7/2006 and 8/5/2009.

Arm/Group Title	Group I (PET Positive)	Group II (PET Negative)	No Mid-Treatment PET
Arm/Group Description	Initially, patients received Rituximab 375 mg/m2 IV Day 1, Cyclophosphamide 750 mg/m2 IV Day 1, Vincristine 1.4 mg/m2 (max: 2 mg) IV Day 1, Doxorubicin 50 mg/m2 IV Day 1, and Prednisone 100 mg/m2 PO Days 1-5 (R-CHOP) every 21 days for 4 cycles. PET scan and conventional restaging occurred between days 14-20 of cycle 3. Patients who were PET positive after 3 cycles of R-CHOP received Rituximab 375 mg/m2 IV Day 1, Ifosfamide 5000 mg/m2 IV over 24 hours Day 2, Carboplatin AUC 5 (max: 800 mg) IV Day 2, Etoposide 100 mg/m2 IV Days 1, 2, 3 (R-ICE), Mesna 5000 mg/m2 IV over 24 hours Day 2, and Filgrastim 5 mcg/kg/day subcutaneous (SC) Day 4 until absolute neutrophil count (ANC) recovery every 14 days for 4 cycles .	Initially, patients received Rituximab 375 mg/m2 IV Day 1, Cyclophosphamide 750 mg/m2 IV Day 1, Vincristine 1.4 mg/m2 (max: 2 mg) IV Day 1, Doxorubicin 50 mg/m2 IV Day 1, and Prednisone 100 mg/m2 PO Days 1-5 (R-CHOP) every 21 days for 4 cycles. PET scan and conventional restaging occurred between days 14-20 of cycle 3. Patients who were PET negative after 3 cycles of R-CHOP received 2 more cycles of R-CHOP (6 cycles in total).	Initially, patients received Rituximab 375 mg/m2 IV Day 1, Cyclophosphamide 750 mg/m2 IV Day 1, Vincristine 1.4 mg/m2 (max: 2 mg) IV Day 1, Doxorubicin 50 mg/m2 IV Day 1, and Prednisone 100 mg/m2 PO Days 1-5 (R-CHOP) every 21 days for 4 cycles. PET scan and conventional restaging occurred between days 14-20 of cycle 3. Patients who did not have mid-treatment PET scan for any reasons came off study and continued to be followed up for disease progression and survival.
Period Title: Step 1 (R-CHOP X 3 Cycles)
STARTED	17	77	6
Treated	17	77	5
Eligible and Treated	13	63	4
COMPLETED	13	63	0
NOT COMPLETED	4	14	6
Period Title: Step 1 (R-CHOP X 3 Cycles)
STARTED	17	76	0
Eligible and Treated	13	61	0
COMPLETED	10	58	0
NOT COMPLETED	7	18	0

Baseline Characteristics

Arm/Group Title	Group I (PET Positive)	Group II (PET Negative)	No Mid-Treatment PET	Total
Arm/Group Description	Initially, patients received Rituximab 375 mg/m2 IV Day 1, Cyclophosphamide 750 mg/m2 IV Day 1, Vincristine 1.4 mg/m2 (max: 2 mg) IV Day 1, Doxorubicin 50 mg/m2 IV Day 1, and Prednisone 100 mg/m2 PO Days 1-5 (R-CHOP) every 21 days for 4 cycles. PET scan and conventional restaging occurred between days 14-20 of cycle 3. Patients who were PET positive after 3 cycles of R-CHOP received Rituximab 375 mg/m2 IV Day 1, Ifosfamide 5000 mg/m2 IV over 24 hours Day 2, Carboplatin AUC 5 (max: 800 mg) IV Day 2, Etoposide 100 mg/m2 IV Days 1, 2, 3 (R-ICE), Mesna 5000 mg/m2 IV over 24 hours Day 2, and Filgrastim 5 mcg/kg/day subcutaneous (SC) Day 4 until absolute neutrophil count (ANC) recovery every 14 days for 4 cycles .	Initially, patients received Rituximab 375 mg/m2 IV Day 1, Cyclophosphamide 750 mg/m2 IV Day 1, Vincristine 1.4 mg/m2 (max: 2 mg) IV Day 1, Doxorubicin 50 mg/m2 IV Day 1, and Prednisone 100 mg/m2 PO Days 1-5 (R-CHOP) every 21 days for 4 cycles. PET scan and conventional restaging occurred between days 14-20 of cycle 3. Patients who were PET negative after 3 cycles of R-CHOP received 2 more cycles of R-CHOP (6 cycles in total).	Initially, patients received Rituximab 375 mg/m2 IV Day 1, Cyclophosphamide 750 mg/m2 IV Day 1, Vincristine 1.4 mg/m2 (max: 2 mg) IV Day 1, Doxorubicin 50 mg/m2 IV Day 1, and Prednisone 100 mg/m2 PO Days 1-5 (R-CHOP) every 21 days for 4 cycles. PET scan and conventional restaging occurred between days 14-20 of cycle 3. Patients who did not have mid-treatment PET scan for any reasons came off study and continued to be followed up for disease progression and survival.	Total of all reporting groups
Overall Participants	13	63	4	80
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	61	63	54	62
Sex: Female, Male (Count of Participants)
Female	4 30.8%	28 44.4%	2 50%	34 42.5%
Male	9 69.2%	35 55.6%	2 50%	46 57.5%

Outcome Measures

1. Primary Outcome

Title	2-year Progression-Free Survival (PFS)
Description	2-year progression-free survival is defined as the probability of patients who remain alive and progression free at 2 years from study entry. The method of Kaplan and Meier (1958) was used to estimate PFS.
Time Frame	Assessed every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group I (PET Negative)	Group II (PET Positive)
Arm/Group Description	Eligible and treated patients who were PET negative after 3 cycles of R-CHOP received 2 more cycles of R-CHOP (6 cycles in total).	Eligible and treated patients who were PET positive after 3 cycles of R-CHOP received 4 cycles of R-ICE.
Measure Participants	61	13
Number (90% Confidence Interval) [probability]	0.76	0.42

2. Secondary Outcome

Title	5-year Overall Survival
Description	5-year overall survival is defined as the probability of patients who remain alive at 5 years from study entry. The method of Kaplan and Meier (1958) was used to estimate overall survival.
Time Frame	Every 4 months if patient is < 2 years from study entry, every 6 months if patient is 2-5 years from study entry, then every 12 months if patient is 5-10 years from study entry.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group I (PET Negative)	Group II (PET Positive)
Arm/Group Description	Eligible and treated patients who were PET negative after 3 cycles of R-CHOP received 2 more cycles of R-CHOP (6 cycles in total).	Eligible and treated patients who were PET positive after 3 cycles of R-CHOP received 4 cycles of R-ICE.
Measure Participants	61	13
Number (90% Confidence Interval) [probability]	0.77	0.69

Adverse Events

Time Frame	Assessed every 3 weeks while on R-CHOP treatment and every 2 weeks while on R-ICE treatment, and for 30 days after the end of treatment, up to 24 weeks.
Arm/Group Title	Step 1 - All Treated Patients		Step 2 - Mid-treatment PET Positive		Step 2 - Mid-treatment PET Negative
Arm/Group Description	All treated patients regardless of eligibility.		Patients who were mid-treatment PET positive and who received R-ICE in step 2 regardless of eligibility.		Patients who were mid-treatment PET negative and who received additional R-CHOP in step 2 regardless of eligibility.
All Cause Mortality
	Step 1 - All Treated Patients		Step 2 - Mid-treatment PET Positive		Step 2 - Mid-treatment PET Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Step 1 - All Treated Patients		Step 2 - Mid-treatment PET Positive		Step 2 - Mid-treatment PET Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/99 (58.6%)		17/17 (100%)		25/76 (32.9%)
Blood and lymphatic system disorders
Anemia	5/99 (5.1%)		7/17 (41.2%)		5/76 (6.6%)
Febrile neutropenia	8/99 (8.1%)		0/17 (0%)		3/76 (3.9%)
Cardiac disorders
Sinus tachycardia	1/99 (1%)		0/17 (0%)		0/76 (0%)
Gastrointestinal disorders
Constipation	1/99 (1%)		0/17 (0%)		0/76 (0%)
Dyspepsia	2/99 (2%)		1/17 (5.9%)		0/76 (0%)
Nausea	3/99 (3%)		1/17 (5.9%)		0/76 (0%)
Perforation, small bowel NOS	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Vomiting	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
General disorders
Fatigue	4/99 (4%)		1/17 (5.9%)		1/76 (1.3%)
Fever w/o neutropenia	1/99 (1%)		0/17 (0%)		1/76 (1.3%)
Immune system disorders
Cytokine release syndrome	1/99 (1%)		0/17 (0%)		0/76 (0%)
Infections and infestations
Colitis, infectious (e.g. C.diff)	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Infection w/ gr3-4 neut, lung	1/99 (1%)		1/17 (5.9%)		0/76 (0%)
Infection w/ gr3-4 neut, peritoneal	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Infection w/ gr3-4 neut, upper airway	1/99 (1%)		0/17 (0%)		0/76 (0%)
Infection w/ gr3-4 neut, urinary tract	1/99 (1%)		0/17 (0%)		0/76 (0%)
Infection w/ gr3-4 neut, vulva	1/99 (1%)		0/17 (0%)		0/76 (0%)
Infection Gr0-2 neut, joint	1/99 (1%)		0/17 (0%)		0/76 (0%)
Infection Gr0-2 neut, larynx	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Infection Gr0-2 neut, upper airway	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Infection w/ gr3-4 neut, blood	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Injury, poisoning and procedural complications
Vascular access,Thrombosis/embolism	1/99 (1%)		0/17 (0%)		0/76 (0%)
Investigations
Leukocytes decreased	35/99 (35.4%)		10/17 (58.8%)		14/76 (18.4%)
Lymphopenia	9/99 (9.1%)		8/17 (47.1%)		6/76 (7.9%)
Neutrophils decreased	41/99 (41.4%)		11/17 (64.7%)		12/76 (15.8%)
Platelets decreased	8/99 (8.1%)		15/17 (88.2%)		5/76 (6.6%)
Weight gain	1/99 (1%)		0/17 (0%)		0/76 (0%)
Coagulation-other	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Aspartate aminotransferase increased	1/99 (1%)		1/17 (5.9%)		0/76 (0%)
Blood bilirubin increased	1/99 (1%)		0/17 (0%)		0/76 (0%)
Metabolism and nutrition disorders
Dehydration	2/99 (2%)		0/17 (0%)		0/76 (0%)
Hypocalcemia	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Hyperglycemia	5/99 (5.1%)		1/17 (5.9%)		1/76 (1.3%)
Hypoglycemia	1/99 (1%)		0/17 (0%)		0/76 (0%)
Hypophosphatemia	1/99 (1%)		1/17 (5.9%)		0/76 (0%)
Hypokalemia	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Hyponatremia	1/99 (1%)		0/17 (0%)		1/76 (1.3%)
Tumor lysis syndrome	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Musculoskeletal and connective tissue disorders
Bone, pain	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Nervous system disorders
Neuropathy-motor	0/99 (0%)		0/17 (0%)		0/76 (0%)
Neuropathy-sensory	0/99 (0%)		0/17 (0%)		0/76 (0%)
Syncope	1/99 (1%)		1/17 (5.9%)		0/76 (0%)
Head/headache	1/99 (1%)		0/17 (0%)		0/76 (0%)
Psychiatric disorders
Insomnia	1/99 (1%)		0/17 (0%)		0/76 (0%)
Renal and urinary disorders
Cystitis	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Respiratory, thoracic and mediastinal disorders
(ARDS)	0/99 (0%)		0/17 (0%)		1/76 (1.3%)
Pneumonitis/pulmonary infiltrates	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Vascular disorders
Hypotension	0/99 (0%)		1/17 (5.9%)		1/76 (1.3%)
Thrombosis/thrombus/embolism	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Other (Not Including Serious) Adverse Events
	Step 1 - All Treated Patients		Step 2 - Mid-treatment PET Positive		Step 2 - Mid-treatment PET Negative
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	97/99 (98%)		17/17 (100%)		75/76 (98.7%)
Blood and lymphatic system disorders
Anemia	73/99 (73.7%)		16/17 (94.1%)		57/76 (75%)
Gastrointestinal disorders
Constipation	52/99 (52.5%)		3/17 (17.6%)		14/76 (18.4%)
Diarrhea w/o prior colostomy	16/99 (16.2%)		2/17 (11.8%)		9/76 (11.8%)
Dyspepsia	6/99 (6.1%)		0/17 (0%)		0/76 (0%)
Muco/stomatitis by exam, oral cavity	9/99 (9.1%)		3/17 (17.6%)		4/76 (5.3%)
Nausea	50/99 (50.5%)		10/17 (58.8%)		25/76 (32.9%)
Salivary	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Vomiting	15/99 (15.2%)		4/17 (23.5%)		3/76 (3.9%)
Abdomen, pain	9/99 (9.1%)		1/17 (5.9%)		0/76 (0%)
Fistula oral cavity	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
General disorders
Fatigue	71/99 (71.7%)		16/17 (94.1%)		50/76 (65.8%)
Fever w/o neutropenia	0/99 (0%)		4/17 (23.5%)		2/76 (2.6%)
Rigors/chills	6/99 (6.1%)		1/17 (5.9%)		0/76 (0%)
Injection site reaction	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Edema limb	5/99 (5.1%)		0/17 (0%)		0/76 (0%)
Pain NOS	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Immune system disorders
Cytokine release syndrome	5/99 (5.1%)		0/17 (0%)		0/76 (0%)
Infections and infestations
Infection w/ unk ANC skin (cellulitis)	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Investigations
Leukocytes decreased	39/99 (39.4%)		8/17 (47.1%)		25/76 (32.9%)
Lymphopenia	11/99 (11.1%)		3/17 (17.6%)		10/76 (13.2%)
Neutrophils decreased	25/99 (25.3%)		3/17 (17.6%)		8/76 (10.5%)
Platelets decreased	23/99 (23.2%)		8/17 (47.1%)		13/76 (17.1%)
Weight loss	6/99 (6.1%)		0/17 (0%)		0/76 (0%)
Alkaline phosphatase increased	22/99 (22.2%)		7/17 (41.2%)		4/76 (5.3%)
Alanine aminotransferase increased	12/99 (12.1%)		3/17 (17.6%)		9/76 (11.8%)
Aspartate aminotransferase increased	20/99 (20.2%)		7/17 (41.2%)		15/76 (19.7%)
Creatinine increased	5/99 (5.1%)		3/17 (17.6%)		1/76 (1.3%)
Metabolic/Laboratory-other	0/99 (0%)		1/17 (5.9%)		1/76 (1.3%)
Metabolism and nutrition disorders
Anorexia	22/99 (22.2%)		6/17 (35.3%)		9/76 (11.8%)
Hypoalbuminemia	11/99 (11.1%)		1/17 (5.9%)		8/76 (10.5%)
Hypercalcemia	5/99 (5.1%)		0/17 (0%)		4/76 (5.3%)
Hypocalcemia	10/99 (10.1%)		3/17 (17.6%)		4/76 (5.3%)
Hyperglycemia	58/99 (58.6%)		9/17 (52.9%)		32/76 (42.1%)
Hypoglycemia	5/99 (5.1%)		0/17 (0%)		0/76 (0%)
Hypomagnesemia	0/99 (0%)		2/17 (11.8%)		2/76 (2.6%)
Hypophosphatemia	0/99 (0%)		3/17 (17.6%)		1/76 (1.3%)
Hypokalemia	6/99 (6.1%)		3/17 (17.6%)		1/76 (1.3%)
Hyponatremia	0/99 (0%)		1/17 (5.9%)		2/76 (2.6%)
Hyperuricemia	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Musculoskeletal and connective tissue disorders
Back, pain	0/99 (0%)		1/17 (5.9%)		1/76 (1.3%)
Bone, pain	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Extremity-limb, pain	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Muscle, pain	14/99 (14.1%)		0/17 (0%)		0/76 (0%)
Nervous system disorders
Taste disturbance	22/99 (22.2%)		3/17 (17.6%)		14/76 (18.4%)
Dizziness	9/99 (9.1%)		2/17 (11.8%)		1/76 (1.3%)
Extrapyramidal movement	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Memory impairment	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Neuropathy-sensory	50/99 (50.5%)		6/17 (35.3%)		39/76 (51.3%)
Depressed level of consciousness	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Head/headache	14/99 (14.1%)		3/17 (17.6%)		2/76 (2.6%)
Psychiatric disorders
Insomnia	27/99 (27.3%)		2/17 (11.8%)		6/76 (7.9%)
Renal and urinary disorders
Urinary hemorrhage NOS	0/99 (0%)		2/17 (11.8%)		0/76 (0%)
Cystitis	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Urinary frequency/urgency	0/99 (0%)		1/17 (5.9%)		1/76 (1.3%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/99 (0%)		1/17 (5.9%)		1/76 (1.3%)
Cough	0/99 (0%)		2/17 (11.8%)		6/76 (7.9%)
Dyspnea	9/99 (9.1%)		4/17 (23.5%)		6/76 (7.9%)
Hiccoughs	0/99 (0%)		2/17 (11.8%)		0/76 (0%)
Nasal cavity/paranasal sinus reaction	0/99 (0%)		2/17 (11.8%)		4/76 (5.3%)
Skin and subcutaneous tissue disorders
Alopecia	58/99 (58.6%)		7/17 (41.2%)		31/76 (40.8%)
Pruritus/itching	5/99 (5.1%)		1/17 (5.9%)		1/76 (1.3%)
Rash/desquamation	6/99 (6.1%)		1/17 (5.9%)		1/76 (1.3%)
Urticaria	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Vascular disorders
Hypertension	5/99 (5.1%)		1/17 (5.9%)		0/76 (0%)
Hypotension	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Flushing	7/99 (7.1%)		1/17 (5.9%)		1/76 (1.3%)
Hot flashes	0/99 (0%)		1/17 (5.9%)		0/76 (0%)
Phlebitis	0/99 (0%)		1/17 (5.9%)		0/76 (0%)

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.