Trial Outcomes & Findings for S1001 PET-Directed Therapy in Treating Patients With Limited-Stage Diffuse Large B-Cell Lymphoma (NCT NCT01359592)

Last Updated: 2025-06-17

Results Overview

Measured from date of registration to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive without report of progression or relapse are censored at date of last contact. Progressions is defined using the 2007 revised Cheson et. Al. criteria, as ≥50% increase in the sum of the products of diameters (SPD) of target measurable lesions, appearance of any new bone marrow involvement, or appearance of any new lesion \>1.5 cm in the longest axis.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

159 participants

Primary outcome timeframe

up to 5 years

Results posted on

2025-06-17

Participant Flow

Patients with nonbulky (\< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy.

Participant milestones

Participant milestones
Measure	R-CHOP x 3 Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	R-CHOP x 6 Chemotherapy for up to 6 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-negative: R-CHOP x 1 Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) Patients start Involved-Field Radiation Therapy (IFRT) as soon as possible after the Day 15-18 PET/CT scan that follows Cycle 3 of R-CHOP, but no later than Day 35 after initiation of Cycle 3 of R-CHOP. Zevalin® treatment begins 3-6 weeks after Radiation Therapy is completed. Radiation Therapy included: IFRT: 180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Radioimmunotherapy included: Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9
Initial Registration STARTED	158	1	0	0
Initial Registration Eligible and Evaluable	132	1	0	0
Initial Registration COMPLETED	129	1	0	0
Initial Registration NOT COMPLETED	29	0	0	0
PET-Directed Therapy STARTED	0	0	137	12
PET-Directed Therapy Eligible and Evaluable	0	0	113	12
PET-Directed Therapy COMPLETED	0	0	111	12
PET-Directed Therapy NOT COMPLETED	0	0	26	0

Reasons for withdrawal

Reasons for withdrawal
Measure	R-CHOP x 3 Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-negative: R-CHOP x 1 Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Initial Registration Adverse Event	1	0
Initial Registration Death	1	0
Initial Registration Other reason not protocol specified	1	0
Initial Registration Ineligible	26	0
PET-Directed Therapy Adverse Event	0	1
PET-Directed Therapy Refusal unrelated to adverse event	0	1
PET-Directed Therapy Ineligible	0	24

Baseline Characteristics

Cell of origin by Lymph2Cx was assessable in 87 patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	R-CHOP x 3 n=132 Participants Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5
Age, Continuous	62 years n=132 Participants
Age, Customized Age > 60 years	71 Participants n=132 Participants
Age, Customized Age <= 60 years	61 Participants n=132 Participants
Sex: Female, Male Female	62 Participants n=132 Participants
Sex: Female, Male Male	70 Participants n=132 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=132 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	121 Participants n=132 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=132 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=132 Participants
Race (NIH/OMB) Asian	8 Participants n=132 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=132 Participants
Race (NIH/OMB) Black or African American	5 Participants n=132 Participants
Race (NIH/OMB) White	115 Participants n=132 Participants
Race (NIH/OMB) More than one race	0 Participants n=132 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=132 Participants
Zubrod Performance Status 0	89 Participants n=132 Participants
Zubrod Performance Status 1	39 Participants n=132 Participants
Zubrod Performance Status 2	4 Participants n=132 Participants
Stage Stage I	82 Participants n=132 Participants
Stage Stage II	50 Participants n=132 Participants
Symptoms A	109 Participants n=132 Participants
Symptoms B	23 Participants n=132 Participants
Elevated Lactate Dehydrogenase (LDH) Yes	19 Participants n=132 Participants
Elevated Lactate Dehydrogenase (LDH) No	113 Participants n=132 Participants
Extranodal Involvement Yes	57 Participants n=132 Participants
Extranodal Involvement No	75 Participants n=132 Participants
Stage-modified International Prognostic Index risk factors 0	35 Participants n=132 Participants
Stage-modified International Prognostic Index risk factors 1	55 Participants n=132 Participants
Stage-modified International Prognostic Index risk factors 2	37 Participants n=132 Participants
Stage-modified International Prognostic Index risk factors 3	5 Participants n=132 Participants
Histologic Subtype Diffuse large B-cell lymphoma, NOS	95 Participants n=132 Participants
Histologic Subtype High-grade B-cell lymphoma with MYC and BCL2 or/and BCL6 rearrangements	4 Participants n=132 Participants
Histologic Subtype High-grade B-cell lymphoma, NOS	22 Participants n=132 Participants
Histologic Subtype T cell/histiocyte-rich large B-cell lymphoma	2 Participants n=132 Participants
Histologic Subtype Central pathologic review not performed	9 Participants n=132 Participants
Cell of Origin by Lymph2Cx GCB	59 Participants n=87 Participants • Cell of origin by Lymph2Cx was assessable in 87 patients
Cell of Origin by Lymph2Cx ABC	20 Participants n=87 Participants • Cell of origin by Lymph2Cx was assessable in 87 patients
Cell of Origin by Lymph2Cx Unclassifiable	8 Participants n=87 Participants • Cell of origin by Lymph2Cx was assessable in 87 patients
Double protein expressors (DPE) DPE	21 Participants n=123 Participants • Double protein expressor status was determined in 123 patients
Double protein expressors (DPE) Non-DPE	97 Participants n=123 Participants • Double protein expressor status was determined in 123 patients
Double protein expressors (DPE) Indeterminate	5 Participants n=123 Participants • Double protein expressor status was determined in 123 patients

PRIMARY outcome

Timeframe: up to 5 years

Population: Eligible and evaluable patients were included in the analysis. The patient who was upstaged at baseline by PET/CT was not included.

Outcome measures

Outcome measures
Measure	R-CHOP x 3 Followed by PET-directed Therapy n=132 Participants R-CHOP x 3: Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 PET-directed therapy included: PET-negative: R-CHOP x 1 PET-positive: IFRT + Yttrium-90 ibritumomab tiuxetan R-CHOP x 1: 1 cycle of R-CHOP, 21 days/cycle Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 IFRT + Yttrium-90 ibritumomab tiuxetan included: IFRT: 180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9	Interim PET-positive Interim PET/CT scan was performed on Day 15-18 of Cycle 3 of R-CHOP chemotherapy. PET/CT scans were centrally reviewed and scored. Positive: 4 uptake \> liver in some sites even if uptake ≤ liver or mediastinum at other sites 5 uptake \> liver in over 90% of sites or development of new uptake consistent with progressive disease	PET-negative: R-CHOP x 1 Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin® Patients start Involved-Field Radiation Therapy (IFRT) as soon as possible after the Day 15-18 PET/CT scan that follows Cycle 3 of R-CHOP, but no later than Day 35 after initiation of Cycle 3 of R-CHOP. Zevalin® treatment begins 3-6 weeks after Radiation Therapy is completed. Radiation Therapy included: IFRT:180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Radioimmunotherapy included: Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9
Five-year Progression-free Survival (PFS) Rate in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma (DLBCL)	87 percentage of participants Interval 79.0 to 92.0	—	—	—

SECONDARY outcome

Timeframe: up to 5 years

Population: Eligible and evaluable patients who had interim PET/CT performed were included in the analysis. The patient who was upstaged at baseline by PET/CT was not included.

Measured from date of interim positron emission tomography (PET)/computed tomography scan to date of first observation of progressive disease, or death due to any cause. Patients last known to be alive without report of progression or relapse are censored at date of last contact.

Outcome measures

Outcome measures
Measure	R-CHOP x 3 Followed by PET-directed Therapy n=114 Participants R-CHOP x 3: Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 PET-directed therapy included: PET-negative: R-CHOP x 1 PET-positive: IFRT + Yttrium-90 ibritumomab tiuxetan R-CHOP x 1: 1 cycle of R-CHOP, 21 days/cycle Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 IFRT + Yttrium-90 ibritumomab tiuxetan included: IFRT: 180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9	Interim PET-positive n=14 Participants Interim PET/CT scan was performed on Day 15-18 of Cycle 3 of R-CHOP chemotherapy. PET/CT scans were centrally reviewed and scored. Positive: 4 uptake \> liver in some sites even if uptake ≤ liver or mediastinum at other sites 5 uptake \> liver in over 90% of sites or development of new uptake consistent with progressive disease	PET-negative: R-CHOP x 1 Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin® Patients start Involved-Field Radiation Therapy (IFRT) as soon as possible after the Day 15-18 PET/CT scan that follows Cycle 3 of R-CHOP, but no later than Day 35 after initiation of Cycle 3 of R-CHOP. Zevalin® treatment begins 3-6 weeks after Radiation Therapy is completed. Radiation Therapy included: IFRT:180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Radioimmunotherapy included: Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9
Progression-free Survival (PFS) Within the PET+ and PET- Subgroups of Patients With Newly Diagnosed Limited-stage Diffuse Large B-Cell Lymphoma (DLBCL)	89 percentage of participants Interval 80.0 to 94.0	86 percentage of participants Interval 54.0 to 96.0	—	—

SECONDARY outcome

Timeframe: up to 4 months or time of disease progression.

Population: Eligible patients who had received any treatment were included in the adverse event summaries. Any CTCAE 4.0 event of Grade 3 (severe), Grade 4 (life threatening), or Grade 5 (fatal) which deemed to be related to protocol treatment are included.

Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.

Outcome measures

Outcome measures
Measure	R-CHOP x 3 Followed by PET-directed Therapy n=132 Participants R-CHOP x 3: Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 PET-directed therapy included: PET-negative: R-CHOP x 1 PET-positive: IFRT + Yttrium-90 ibritumomab tiuxetan R-CHOP x 1: 1 cycle of R-CHOP, 21 days/cycle Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 IFRT + Yttrium-90 ibritumomab tiuxetan included: IFRT: 180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9	Interim PET-positive n=1 Participants Interim PET/CT scan was performed on Day 15-18 of Cycle 3 of R-CHOP chemotherapy. PET/CT scans were centrally reviewed and scored. Positive: 4 uptake \> liver in some sites even if uptake ≤ liver or mediastinum at other sites 5 uptake \> liver in over 90% of sites or development of new uptake consistent with progressive disease	PET-negative: R-CHOP x 1 n=113 Participants Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin® n=12 Participants Patients start Involved-Field Radiation Therapy (IFRT) as soon as possible after the Day 15-18 PET/CT scan that follows Cycle 3 of R-CHOP, but no later than Day 35 after initiation of Cycle 3 of R-CHOP. Zevalin® treatment begins 3-6 weeks after Radiation Therapy is completed. Radiation Therapy included: IFRT:180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Radioimmunotherapy included: Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Cough	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Diarrhea	2 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypertension	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Lymphocyte count decreased	16 Participants	0 Participants	9 Participants	2 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Skin infection	1 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Stroke	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Thromboembolic event	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Urinary tract infection	3 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Weight loss	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Alanine aminotransferase increased	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Anemia	7 Participants	0 Participants	2 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Anorexia	1 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Bone pain	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug CD4 lymphocytes decreased	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Catheter related infection	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Dyspnea	3 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Edema limbs	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Endocrine disorders - Other, specify	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Fall	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Fatigue	3 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Febrile neutropenia	13 Participants	0 Participants	2 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Generalized muscle weakness	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hyperglycemia	3 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypocalcemia	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypokalemia	2 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hyponatremia	1 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypotension	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypoxia	0 Participants	0 Participants	2 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Leukemia secondary to oncology chemotherapy	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Lung infection	2 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Nausea	1 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Nervous system disorders - Other, specify	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Neutrophil count decreased	34 Participants	0 Participants	11 Participants	2 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Peripheral sensory neuropathy	1 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Platelet count decreased	5 Participants	0 Participants	4 Participants	3 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Resp, thoracic and mediastinal disorders - Other	0 Participants	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Sepsis	2 Participants	0 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug White blood cell decreased	26 Participants	0 Participants	12 Participants	2 Participants

SECONDARY outcome

Timeframe: up to 5 years

Population: Eligible and evaluable patients were included in the analysis. The patient who was upstaged at baseline by PET/CT was not included.

Measured from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

Outcome measures

Outcome measures
Measure	R-CHOP x 3 Followed by PET-directed Therapy n=132 Participants R-CHOP x 3: Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 PET-directed therapy included: PET-negative: R-CHOP x 1 PET-positive: IFRT + Yttrium-90 ibritumomab tiuxetan R-CHOP x 1: 1 cycle of R-CHOP, 21 days/cycle Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 IFRT + Yttrium-90 ibritumomab tiuxetan included: IFRT: 180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9	Interim PET-positive Interim PET/CT scan was performed on Day 15-18 of Cycle 3 of R-CHOP chemotherapy. PET/CT scans were centrally reviewed and scored. Positive: 4 uptake \> liver in some sites even if uptake ≤ liver or mediastinum at other sites 5 uptake \> liver in over 90% of sites or development of new uptake consistent with progressive disease	PET-negative: R-CHOP x 1 Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin® Patients start Involved-Field Radiation Therapy (IFRT) as soon as possible after the Day 15-18 PET/CT scan that follows Cycle 3 of R-CHOP, but no later than Day 35 after initiation of Cycle 3 of R-CHOP. Zevalin® treatment begins 3-6 weeks after Radiation Therapy is completed. Radiation Therapy included: IFRT:180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Radioimmunotherapy included: Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9
Overall Survival of Patients With Newly Diagnosed Limited-stage Diffuse Large B-Cell Lymphoma (DLBCL)	89 percentage of participants Interval 82.0 to 93.0	—	—	—

SECONDARY outcome

Timeframe: Up to 4 months

Population: Eligible and evaluable patients who treated with PET-directed therapy based on FDG-PET imaging after 3 cycles of R-CHOP were included in the analysis.

Complete Response (CR) is a complete disappearance of all disease with the exception of the following. If no PET scan or when the PET scan was positive before therapy, a post-treatment residual mass of any size is permitted if it is PET negative. If the PET scan was negative before therapy, all nodal masses at baseline must have regressed. No new lesions. Previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response (PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. If PET scan or when the PET scan was positive before therapy, PET should be positive in at least one previously involved site.

Outcome measures

Outcome measures
Measure	R-CHOP x 3 Followed by PET-directed Therapy n=113 Participants R-CHOP x 3: Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 PET-directed therapy included: PET-negative: R-CHOP x 1 PET-positive: IFRT + Yttrium-90 ibritumomab tiuxetan R-CHOP x 1: 1 cycle of R-CHOP, 21 days/cycle Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 IFRT + Yttrium-90 ibritumomab tiuxetan included: IFRT: 180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9	Interim PET-positive n=12 Participants Interim PET/CT scan was performed on Day 15-18 of Cycle 3 of R-CHOP chemotherapy. PET/CT scans were centrally reviewed and scored. Positive: 4 uptake \> liver in some sites even if uptake ≤ liver or mediastinum at other sites 5 uptake \> liver in over 90% of sites or development of new uptake consistent with progressive disease	PET-negative: R-CHOP x 1 Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin® Patients start Involved-Field Radiation Therapy (IFRT) as soon as possible after the Day 15-18 PET/CT scan that follows Cycle 3 of R-CHOP, but no later than Day 35 after initiation of Cycle 3 of R-CHOP. Zevalin® treatment begins 3-6 weeks after Radiation Therapy is completed. Radiation Therapy included: IFRT:180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Radioimmunotherapy included: Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9
Response Rates in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma Using PET/CT Scan to Direct Therapy After 3 Cycles of R-CHOP Complete Response	112 Participants	8 Participants	—	—
Response Rates in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma Using PET/CT Scan to Direct Therapy After 3 Cycles of R-CHOP Partial Response	0 Participants	4 Participants	—	—
Response Rates in Patients With Newly Diagnosed Limited Stage Diffuse Large B-cell Lymphoma Using PET/CT Scan to Direct Therapy After 3 Cycles of R-CHOP Inadequate Assessment	1 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: 5 years

Formalin-fixed, paraffin-embedded tissue from the diagnostic biopsy is collected and used to determine germinal center B-cell (GCB) phenotype. GCB subtype of DLBCL is defined by gene-expression profiling that is performed using quantitative nuclease protection assay (qNPA). Data for this outcome measure is not available at this time. We expect this data to be available by December 2025.

Outcome measures

Outcome data not reported

Adverse Events

R-CHOP x 3

Serious events: 2 serious events

Other events: 130 other events

Deaths: 1 deaths

R-CHOP x 6

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

PET-negative: R-CHOP x 1

Serious events: 2 serious events

Other events: 105 other events

Deaths: 1 deaths

PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin®)

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	R-CHOP x 3 n=132 participants at risk Chemotherapy for up to 3 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	R-CHOP x 6 n=1 participants at risk Chemotherapy for up to 6 cycles, 21 days/per cycle, with R-CHOP For each cycle, R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5	PET-negative: R-CHOP x 1 n=113 participants at risk Chemotherapy for 1 cycle, 21 days/per cycle, with R-CHOP R-CHOP therapy included: Rituximab: 375 mg/m\^2 IV administration on Day 1 Cyclophosphamide: 750 mg/m\^2 IV administration on Day 1 Doxorubicin: 50 mg/m\^2 IV administration on Day 1 Vincristine: 1.4 mg/m\^2 (maximum 2 mg) IV administration on Day 1 Prednisone: 100 mg administered orally on Days 1 through 5 2	PET-positive: IFRT + Yttrium-90 Ibritumomab Tiuxetan (Zevalin®) n=12 participants at risk Patients start Involved-Field Radiation Therapy (IFRT) as soon as possible after the Day 15-18 PET/CT scan that follows Cycle 3 of R-CHOP, but no later than Day 35 after initiation of Cycle 3 of R-CHOP. Zevalin® treatment begins 3-6 weeks after Radiation Therapy is completed. Radiation Therapy included: IFRT: 180 cGy/day for a minimum dose of 3600 cGy and a maximum of dose of 4500 cGy Radioimmunotherapy included: Rituximab: 250 mg/m\^2 IV administration on Day 1 then 7, 8, or 9 Yttrium-90 ibritumomab tiuxetan: 0.4 mCi/kg or 0.3 mCi/kg, absolute maximum allowable dose of 32.0 mCi, 10 min IV infusion, on Day 7, 8 or 9
General disorders Sudden death NOS	0.76% 1/132 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/1 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/113 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/12 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.
Infections and infestations Sepsis	0.76% 1/132 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/1 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/113 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/12 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukemia secondary to oncology chemotherapy	0.00% 0/132 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/1 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.88% 1/113 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/12 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/132 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/1 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.88% 1/113 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/12 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.
Respiratory, thoracic and mediastinal disorders Resp, thoracic and mediastinal disorders - Other	0.00% 0/132 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/1 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.88% 1/113 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.	0.00% 0/12 • up to 4 months or time of disease progression The total number or participants at risk in this section is the number or participants in each arm that are eligible and evaluable.

Other adverse events

Additional Information

Lymphoma Committee Statistician

SWOG Statistics and Data Management Center

Phone: 206-667-4623

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60