Trial Outcomes & Findings for S1106 Rituximab With Combination Chemotherapy or Bendamustine Hydrochloride Followed by Consolidation Chemotherapy and Stem Cell Transplantation in Older Patients With Previously Untreated Mantle Cell Lymphoma (NCT NCT01412879)

Last Updated: 2021-10-29

Results Overview

Disease progression is defined using the 2007 revised Cheson et al. criteria that is at least 50% increase in sum of the product of the diameters (SPD) of target measurable nodal lesions over the smallest sum observed, or \>= 50% increase in greatest transverse diameter (GTD) of any nodal \> 1 cm in shortest axis, or \>= 50% increase in the SPD of other target measurable lesions over the smallest sum observed, any new bone marrow involvement, any new lesion, lymph node with long axis is \> 1.5 cm or if both long and short axes are \> 1 cm, PET positive if patients with no pretreatment PET scan or when PET scan was positive before therapy. Progression-free survival is 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 and progression-free are censored at date of last contact.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

53 participants

Primary outcome timeframe

Up to 2 years

Results posted on

2021-10-29

Participant Flow

Participant milestones

Participant milestones
Measure	Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	Arm 2: R-Bendamustine (Induction Therapy) R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.	Consolidation Therapy: Stem Cell Transplant Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)\\ twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. \* \*TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Initial Registration (Induction Therapy) STARTED	18	35	0
Initial Registration (Induction Therapy) Treatment Started	17	35	0
Initial Registration (Induction Therapy) COMPLETED	5	27	0
Initial Registration (Induction Therapy) NOT COMPLETED	13	8	0
Consolidation Therapy STARTED	0	0	26
Consolidation Therapy COMPLETED	0	0	26
Consolidation Therapy NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	Arm 2: R-Bendamustine (Induction Therapy) R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.
Initial Registration (Induction Therapy) Adverse Event	5	3
Initial Registration (Induction Therapy) Refusal Unrelated to Adverse Event	1	3
Initial Registration (Induction Therapy) Progression/Relapse	0	1
Initial Registration (Induction Therapy) Reasons not Protocol Specified	6	1
Initial Registration (Induction Therapy) Treatment not Given	1	0

Baseline Characteristics

S1106 Rituximab With Combination Chemotherapy or Bendamustine Hydrochloride Followed by Consolidation Chemotherapy and Stem Cell Transplantation in Older Patients With Previously Untreated Mantle Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) n=17 Participants The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	Arm 2: R-Bendamustine (Induction Therapy) n=35 Participants R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.	Total n=52 Participants Total of all reporting groups
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=93 Participants	1 Participants n=4 Participants	3 Participants n=27 Participants
Age, Continuous	58.8 years n=93 Participants	56.6 years n=4 Participants	57.2 years n=27 Participants
Sex: Female, Male Female	8 Participants n=93 Participants	3 Participants n=4 Participants	11 Participants n=27 Participants
Sex: Female, Male Male	9 Participants n=93 Participants	32 Participants n=4 Participants	41 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=93 Participants	35 Participants n=4 Participants	51 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants
Race (NIH/OMB) White	13 Participants n=93 Participants	32 Participants n=4 Participants	45 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 2 years

Population: All eligible patients who started treatment were included in the analysis

Outcome measures

Outcome measures
Measure	Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) n=17 Participants The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	Arm 2: R-Bendamustine (Induction Therapy) n=35 Participants R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.	Stem Cell Transplant (Consolidation Therapy) Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)\\ twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. \* \*TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Progression-Free Survival (PFS) at 2 Years	82 percentage of participants Interval 53.0 to 93.7	81 percentage of participants Interval 62.7 to 91.1	—

SECONDARY outcome

Timeframe: Up to 8 months (Assessed at the beginning of each cycle of treatment, at restaging, and at post transplant.)

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	Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) n=17 Participants The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	Arm 2: R-Bendamustine (Induction Therapy) n=35 Participants R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.	Stem Cell Transplant (Consolidation Therapy) n=26 Participants Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)\\ twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. \* \*TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Acidosis	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Adult respiratory distress syndrome	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Alanine aminotransferase increased	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Anemia	10 Participants	3 Participants	9 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Anorexia	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Arthralgia	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Aspartate aminotransferase increased	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Blood bilirubin increased	0 Participants	0 Participants	2 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug CD4 lymphocytes decreased	2 Participants	2 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	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Dehydration	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Device related infection	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Diarrhea	1 Participants	0 Participants	4 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Enterocolitis	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Enterocolitis infectious	0 Participants	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Epistaxis	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Fatigue	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	5 Participants	5 Participants	13 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Gallbladder infection	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hyperglycemia	2 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypoalbuminemia	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	2 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypokalemia	5 Participants	2 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypomagnesemia	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hyponatremia	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypophosphatemia	4 Participants	1 Participants	3 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
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Hypoxia	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Infections and infestations - Other, specify	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Infusion related reaction	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	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Lymphocyte count decreased	10 Participants	27 Participants	12 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Myalgia	0 Participants	1 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	2 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Neutrophil count decreased	11 Participants	12 Participants	16 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Pain in extremity	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	12 Participants	6 Participants	19 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Pruritus	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Rash maculo-papular	1 Participants	1 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Rectal hemorrhage	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Small intestinal obstruction	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Sore throat	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Syncope	1 Participants	0 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Tumor pain	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	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Vascular access complication	0 Participants	1 Participants	0 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug Vomiting	0 Participants	0 Participants	1 Participants
Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug White blood cell decreased	10 Participants	14 Participants	20 Participants

SECONDARY outcome

Timeframe: Up to 9 months

Population: All eligible patients who started treatment 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	Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) n=17 Participants The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	Arm 2: R-Bendamustine (Induction Therapy) n=35 Participants R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.	Stem Cell Transplant (Consolidation Therapy) Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)\\ twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. \* \*TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Response Rate (Complete and Partial Response)	94.1 percentage of participants Interval 71.3 to 99.9	82.9 percentage of participants Interval 66.4 to 93.4	—

SECONDARY outcome

Timeframe: Up to 5 years

Population: All eligible patients who started treatment were included in the analysis.

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

Outcome measures

Outcome measures
Measure	Arm 1: R-HCVAD/MTX/Ara-C (Induction Therapy) n=17 Participants The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	Arm 2: R-Bendamustine (Induction Therapy) n=35 Participants R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.	Stem Cell Transplant (Consolidation Therapy) Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)\\ twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. \* \*TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
5-year Overall Survival (OS)	81 percentage of participants Interval 50.6 to 93.3	79 percentage of participants Interval 57.1 to 90.1	—

Adverse Events

R-HCVAD/MTX/Ara-C (Induction Therapy)

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

R-Bendamustine (Induction Therapy)

Serious events: 0 serious events

Other events: 35 other events

Deaths: 0 deaths

Stem Cell Transplant (Consolidation Therapy)

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	R-HCVAD/MTX/Ara-C (Induction Therapy) n=17 participants at risk The R-HCVAD/MTX/ARA-C combination are rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine. Cycle 1 and 3: Patients receive induction therapy comprising rituximab IV on day 1; cyclophosphamide IV over 3 hours every 12 hours on days 2-4; doxorubicin hydrochloride IV over 72 hours on days 5-7; vincristine sulfate IV on days 5 and 12; and dexamethasone IV or orally (PO) once daily (QD) on days 2-5 and 12-15. Patients with responsive disease after course 1 proceed to course 2. Cycle 2 and 4: Patients receive rituximab IV on day 1; methotrexate IV over 2-22 hours on day 2; cytarabine IV over 2 hours every 12 hours on days 3-4; and leucovorin calcium PO or IV on days 3-6. Patients undergo stem cell collection after completion of Cycle 2 (1 cycle = 21 days).	R-Bendamustine (Induction Therapy) n=35 participants at risk R-bendamustine combinations are rituximab and bendamustine. Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1-2. Treatment repeats every 28 days for 4 cycles (1 cycle = 28 days). Patients with responsive disease receive 2 additional cycles of treatment. Patients undergo stem cell collection after completion of 6 Cycles of treatment.	Stem Cell Transplant (Consolidation Therapy) n=26 participants at risk Patients receive stem cell transplant with non-TBI containing regimen (BCV or BEAM Chemotherapy) for patients 61 years or older or TBI-containing regimen (TBI/VP-16/Cyclophosphamide). BCV chemotherapy: Carmustine IV over 2 hours on days -6 to -4; etoposide IV over 4 hours on day -4; and cyclophosphamide IV over 1 hour on day -2. BEAM chemotherapy: Carmustine IV over 4 hours on days -7 and -6; etoposide IV over 1 hour twice daily and cytarabine IV over 2 hours twice daily on days -5 to -2, and melphalan IV on day -1. TBI, etoposide, cyclophosphamide: Patients undergo total-body irradiation (TBI)\\ twice daily on days -8 to -5. Patients also receive etoposide IV on day -4 and cyclophosphamide IV over 1 hour on day -2. \* \*TBI may not be used for patients 61 years of age and older. Stem cell transplantation: Patients then undergo autologous peripheral blood stem cell transplantation on day 0.
Gastrointestinal disorders Diarrhea	0.00% 0/17 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).	0.00% 0/35 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).	3.8% 1/26 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).
Infections and infestations Enterocolitis infectious	0.00% 0/17 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).	0.00% 0/35 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).	3.8% 1/26 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).
Respiratory, thoracic and mediastinal disorders Adult respiratory distress syndrome	0.00% 0/17 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).	0.00% 0/35 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).	3.8% 1/26 • Up to 8 months (assessed at the beginning of each cycle of treatment, at restaging, and at post transplant).

Other adverse events

Additional Information

Lymphoma Committee Statistician

SWOG Statistical Center

Phone: 206-667-4623

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place