Trial Outcomes & Findings for Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma (NCT NCT02853370)

Last Updated: 2023-02-01

Results Overview

Percentage of patients with complete response. Complete response to be assessed by means of CT-scan, Immunophenotype in blood and bone marrow (PET-scan optional) Complete response (CR) requires the disappearance of all evidence of disease 1. Regression to normal size on CT of organomegaly (splenomegaly, hepatomegaly and lymphoadenopathies) 2. Normalization of the blood counts (Hb \>12 g/dl; platelets \>100.000/mm3; neutrophils \>1.500/mm3 and no evidence of circulating clonal B-cells) 3. No evidence or minor (\<5%) BM infiltration detected by immunohistochemistry

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

78 participants

Primary outcome timeframe

At the end of treatment (After 24 weeks of treatment)

Results posted on

2023-02-01

Participant Flow

Recruitment lasted from 03 December 2012 to 13 November 2014

78 patients were screened and 56 patients were eligible: 16 patients were ineligible for unconfirmed diagnosis of SMZL, 3 for age \>80 years, 1 for withdrawal of the Informed Consent, 1 for treatment not started and 1 urgent treatment needed.

Participant milestones

Participant milestones
Measure	Bendamustine and Rituximab Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
Overall Study STARTED	56
Overall Study COMPLETED	45
Overall Study NOT COMPLETED	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Bendamustine and Rituximab Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
Overall Study Physician Decision	1
Overall Study Lack of Efficacy	2
Overall Study Death	1
Overall Study Adverse Event	4
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
Age, Categorical <=18 years	0 Participants n=56 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=56 Participants
Age, Categorical >=65 years	32 Participants n=56 Participants
Sex: Female, Male Female	23 Participants n=56 Participants
Sex: Female, Male Male	33 Participants n=56 Participants
Region of Enrollment Italy	38 participants n=56 Participants
Region of Enrollment France	18 participants n=56 Participants
ECOG Performance Status Grade 2	2 Participants n=56 Participants
ECOG Performance Status Grade 0 - 1	51 Participants n=56 Participants
ECOG Performance Status Not recorded	3 Participants n=56 Participants
Bone Marrow (BM) Involvement BM Involvement	56 Participants n=56 Participants
Bone Marrow (BM) Involvement No BM Involvement	0 Participants n=56 Participants
Thoracic and / or abdominal lymphadenopathy Thoracic and / or abdominal lymphadenopathy	34 Participants n=56 Participants
Thoracic and / or abdominal lymphadenopathy No Thoracic and / or abdominal lymphadenopathy	22 Participants n=56 Participants
Extranodal Involvement Extranodal Involvement	2 Participants n=56 Participants
Extranodal Involvement No Extranodal Involvement	54 Participants n=56 Participants
IIL Prognostic Score Low (0)	22 Participants n=56 Participants
IIL Prognostic Score Intermediate (1)	14 Participants n=56 Participants
IIL Prognostic Score High (2 - 3)	19 Participants n=56 Participants
IIL Prognostic Score Not recorded	1 Participants n=56 Participants

PRIMARY outcome

Timeframe: At the end of treatment (After 24 weeks of treatment)

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
Complete Response Rate (CRR)	73 Percentage of patients Interval 60.0 to 84.0

SECONDARY outcome

Timeframe: At the end of treatment (After 24 weeks of treatment)

Percentage of patients with complete and partial response. Partial response (PR) requires regression of 50% or greater in the measurable disease manifestations and no new sites of disease. This should include: resolution or decrease in spleen size, improvement on cytopenias and resolution or decrease in lymphadenopathy if present. Bone Marrow should show a decrease in the level of lymphoid infiltration and improvement of the haemopoietic reserve

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
Overall Response Rate (ORR)	91 Percentage of patients Interval 80.0 to 97.0

SECONDARY outcome

Timeframe: 3 years after study entry

Percentage of patients free from disease progression after 3 years from study entry. Progression is defined as reappearance of cytopenia or lymphoma relapse/ progression with enlarged lymph node(s) or spleen if present, histologic transformation or death as a result of any cause.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
3-year Progression Free Survival (PFS)	90 Percentage of patients Interval 77.0 to 96.0

SECONDARY outcome

Timeframe: 3 years from study entry

Percentage of responding patients after 3 years from study entry. DOR is defined for all patients who achieved a response (CR and PR)

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
3-years Duration of Response (DOR)	93 Percentage of patients Interval 81.0 to 98.0

SECONDARY outcome

Timeframe: 3 years after study entry

Percentage of patients free from events after 3 years from study entry. Events are defined as any treatment failure including disease progression, or discontinuation of treatment for any cause (eg, disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death).

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
3-years Event Free Survival (EFS)	80 Percentage of patients Interval 65.0 to 89.0

SECONDARY outcome

Timeframe: 3 years after treatment start

Percentage of patients alive after 3 years from study entry

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
3-years Overall Survival Rate	96 Percentage of patients Interval 84.0 to 98.0

SECONDARY outcome

Timeframe: Five years after study entry

Percentage of patients free from disease progression after 5 years from treatment start. Progression is defined as reappearance of cytopenia or lymphoma relapse/ progression with enlarged lymph node(s) or spleen if present, histologic transformation or death as a result of any cause.

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
5 Years Progression Free Survival (PFS) -	83 Percentage of patients Interval 71.0 to 91.0

SECONDARY outcome

Timeframe: Five years after study entry

Percentage of patients alive after 5 years from study entry

Outcome measures

Outcome measures
Measure	Bendamustine and Rituximab n=56 Participants Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
5 Years Overall Survival (OS)	93 Percentage of patients Interval 82.0 to 97.0

Adverse Events

Bendamustine and Rituximab

Serious events: 14 serious events

Other events: 50 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Bendamustine and Rituximab n=56 participants at risk Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
Surgical and medical procedures Angioplasty	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Investigations Pancytopenia	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant peripheral nerve sheath tumor	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Myelodysplastic syndrome	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Blood and lymphatic system disorders Coagulation disorders	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Blood and lymphatic system disorders Febrile neutropenia	7.1% 4/56 • Number of events 5 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Blood and lymphatic system disorders Anaemia	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
General disorders Infusion related reaction	1.8% 1/56 • Number of events 2 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
General disorders Paraneoplastic fever	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Skin and subcutaneous tissue disorders Erythroderma	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Metabolism and nutrition disorders Tumour lysis syndrome	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Infections and infestations Sepsis	3.6% 2/56 • Number of events 2 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Infections and infestations Lung infection	1.8% 1/56 • Number of events 1 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .

Other adverse events

Other adverse events
Measure	Bendamustine and Rituximab n=56 participants at risk Induction Phase (Cycle 1 to Cycle 3 ): Bendamustine 90 mg/sqm i.v. d1 \& d2 or d2 \& d3 Rituximab 375 mg/m2 i.v. d1 Extended Phase (Cycle 4 to Cycle 6): Bendamustine 90 mg/sqm i.v. d1 \& d2 Rituximab 375 mg/m2 i.v. d1
Blood and lymphatic system disorders Anaemia	42.9% 24/56 • Number of events 42 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Blood and lymphatic system disorders Leukopenia	50.0% 28/56 • Number of events 82 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Blood and lymphatic system disorders Neutropenia	55.4% 31/56 • Number of events 98 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Blood and lymphatic system disorders Thrombocytopenia	46.4% 26/56 • Number of events 51 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Investigations Investigations	5.4% 3/56 • Number of events 4 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders	7.1% 4/56 • Number of events 10 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Nervous system disorders Nervous system disorders	5.4% 3/56 • Number of events 3 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
General disorders General disorders and administration site conditions	23.2% 13/56 • Number of events 22 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Gastrointestinal disorders Gastrointestinal disorders	41.1% 23/56 • Number of events 37 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Skin and subcutaneous tissue disorders Skin disorder	17.9% 10/56 • Number of events 19 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .
Infections and infestations Infections	12.5% 7/56 • Number of events 17 • All Adverse Events (AEs): from the date of informed consent signature until 30 days after last treatment administration (8 months). Serious AEs suspected to be related to the study: until the end of study (5 years) .

Additional Information

Dr. Emilio Iannitto

U.O.C. Haematology - A.O.U. Policlinico Paolo Giaccone, Palermo (Italy)

Phone: +39 091 6554415

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place