Neoplasms

Blood and Lymph Conditions

All Conditions

Immune System Diseases

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Lymphoid

Leukemia, Lymphocytic, Chronic, B-Cell

Neoplasms by Histologic Type

Hematologic Diseases

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Antineoplastic Agents

All Drugs and Chemicals

Antirheumatic Agents

Bendamustine Hydrochloride

Rituximab

Antineoplastic Agents, Immunological

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Patients receive bendamustine hydrochloride 90mg/m2 IV on days 1 and 2 each cycle. Patients also receive rituximab 375 mg/m2 IV on day 1 at first cycle and 500 mg/m2 on day 1 all subsequent cycles.

Patients receive bendamustine and rituximab. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Bendamustine and Rituximab

Martin Spacek, MD, PhD

The purpose of this observational study is to provide additional data to confirm the safety profile and efficacy of bendamustine and rituximab (BR) chemotherapy for chronic lymphocytic leukemia patients with significant comorbidities treated in routine clinical practice.

BR (bendamustine, rituximab) combination is currently accepted as a first-line treatment of chronic lymphocytic leukemia (CLL) in patients for whom fludarabine combination chemotherapy is not appropriate.

The objective of this observational study is to provide additional data to confirm the safety profile and efficacy of BR for CLL patients treated in routine clinical practice.

Specific data of interest are: comorbid conditions, CLL characteristics, adverse events, reasons for discontinuation BR, overall response rates, complete response rate, progression-free survival, overall survival.

Observational Study in CLL Patients Receiving BR

Observational Study in Comorbid Patients With Chronic Lymphocytic Leukemia Receiving First-line Bendamustine With Rituximab

Toxicity assessed by Common Toxicity Criteria for Adverse Effects (CTCAE) criteria (myelotoxicity, infections, etc.)

Response to treatment was assessed using National Cancer Institute-sponsored Working Group criteria, including bone marrow examination and radiographic confirmation of complete response.

Calculated from the start of therapy until disease progression or death

Time interval from the start of therapy until death form any cause

Czech CLL Study Group

Lymphoma

Lymphoma, Non-Hodgkin

Lymphosarcoma

open-label, single arm, clinical trial of bendamustine (SDX-105) plus rituximab

Patients will receive rituximab on the first day of a cycle at a dose of 375 mg/m2, followed on the second and third day of a cycle by SDX-105 (bendamustine) at a dose of 90 mg/m2/day of treatment. Four cycles are planned. Patients will receive a dose of rituximab alone 7 days prior to the first cycle of the combination and a dose of rituximab 28 days after the last cycle of the combination. If there is documented disease regression, a fifth and sixth cycle of SDX-105 plus rituximab may be administered.

bendamustine and rituximab

SUMMARY:

This is an open label study combining Rituxan and SDX-105. Rituxan will be given on day 1 followed by a 30-60 minute intravenous infusion of SDX-105 on day 2 and day 3. Treatment will repeat every 21 days (a cycle). Treatment can continue for up to 6 cycles (about 4 months) if tumor status improves and there are no unacceptable side effects. Patients will be followed for up to 2 years or until disease progression.

RATIONALE:

Rituxan has been shown to increase the sensitivity of cells to chemotherapy. The combination of SDX-105 and Rituxan has been effective in both the laboratory and in a recent clinical study with Non-Hodgkin's lymphoma patients.

PURPOSE:

This study will evaluate the safety and effectiveness of SDX-105 plus Rituxan in patients with Non-Hodgkin's lymphoma who have relapsed after taking Rituxan.

SDX-105 in Combination With Rituxan for Patients With Relapsed Indolent or Mantle Cell Non-Hodgkin's Lymphoma (NHL)

A Multi-Center Phase II Study to Investigate the Safety and Activity of SDX-105 (Bendamustine) in Combination With Rituximab in Patients With Relapsed Indolent or Mantle Cell Non-Hodgkin's Lymphoma (NHL)

Cephalon

Lymphoma, B-Cell, Marginal Zone

Lymphoma, B-Cell

B-cell Lymphoma

Marginal Zone Lymphoma

Induction Phase (Cycle 1 to Cycle 3 ):

Bendamustine 90 mg/sqm i.v. d1 \& d2\* 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

From Cycle 4 to Cycle 6, every 4 weeks, depending on the response after the first 3 Cycles

\*Or days 2-3 according to institutional/patient/physician preference

\*\*Administration of Rituximab during cycle 1 and cycle 2 can be postponed to day 8 or 14 in case of risk of tumor lysis syndrome (TLS)

Emilio Iannitto, MD

Splenic Marginal Zone Lymphoma (SMZL) is a well-defined low-grade B-cell lymphoma,considered as a rare neoplasm accounting for about 2% of all non-Hodgkin's lymphomas (NHL) and represents for most cases of otherwise unclassifiable chronic lymphoid B-cell cluster of differentiation antigen 5 (CD5)-lymphoproliferative disorders. SMZL is characterized by an almost exclusive involvement of the spleen and bone marrow and in about 25% of cases the disease pursues an aggressive course and most patients die of lymphoma progression within 3-4 years.

Retrospective studies have indicated that purine analogous achieved very high response rates in both naïve and pre-treated patients. Moreover, the introduction of the anti-cluster of differentiation antigen 20 (CD20) humanized antibody rituximab, either used alone or in combination with chemotherapy has been reported to be very effective in producing a rapid clearance of neoplastic cells.

Prospective, multicenter, open-label, phase II study, designed to determine efficacy and safety of a Chemo-immunotherapy with the combination of bendamustine + rituximab in patients with splenic marginal zone lymphoma.

Study Population: previously untreated (except for splenectomy and/or antiviral therapy for Hepatitis C Virus (HCV) infection) and symptomatic Splenic Marginal Zone patients.

Objectives: evaluation of the efficacy and the safety of R-Bendamustine in symptomatic Splenic Marginal Zone Lymphoma patients.

Primary Objective: efficacy of R-Bendamustine measured by Complete Response rate. Complete response rate defined as regression to normal size on CT of organomegaly (spleen, liver, lymph nodes); normalization of the blood counts and no evidence of circulating clonal cells, and no evidence or minor (≤ 5%) Bone Marrow (BM) infiltration detected by immunohistochemistry (IHC).

Treatment: The R-Bendamustine regimen consisted of 28-day cycle. Patients achieving a complete response (CR) after 3 cycles received only one more cycle of R-Bendamustine, while those achieving a partial response (PR) received 3 additional cycles of R-Bendamustine; if less than PR patients were withdrawn from the study

Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma

Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma. The International Extranodal Lymphoma Study Group (IELSG) 36 Phase II Prospective Study

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

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

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.

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

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).

Percentage of patients alive after 3 years from 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.

Percentage of patients alive after 5 years from study entry

International Extranodal Lymphoma Study Group (IELSG)

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

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Italy

France

Region of Enrollment

WHO performance status scale:

0 - Able to carry out all normal activity without restriction

1. - Restricted in physically strenuous activity but ambulatory and able to carry out light work
2. - Ambulatory and capable of all self-care but unable to carry out any work; up and about more than 50% of waking hours
3. - Capable of only limited self-care; confined to bed or chair more than 50% of waking hours
4. - Completely disabled; cannot carry on any self-care; totally confined to bed or chair

ECOG Performance Status

Bone Marrow (BM) Involvement

Thoracic and / or abdominal lymphadenopathy

Extranodal Involvement

The Lymphoma Italian Intergroup (IIL) have proposed a clinical score based on three parameters:

1. Haemoglobin \< 12 gr/dL
2. LDH \> ULN
3. Albumin \< 3.5 gr/dL

Score:

Low Risk non adverse factor; Intermediate Risk 1 adverse factor; High Risk 2-3 adverse factors.

IIL Prognostic Score

Dr. Emilio Iannitto

Complete Response Rate (CRR)

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Observational Study in CLL Patients Receiving BR	NCT02381899	Chronic Lymphoc...	Bendamustine an...	18 Years -	Czech CLL Study Group
SDX-105 in Combination With Rituxan for Patients With Relapsed Indolent or Mantle Cell Non-Hodgkin's Lymphoma (NHL)	NCT00076349	Non-Hodgkin's L...	bendamustine an...	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
SDX-105 in Combination With Rituxan for Patients With Relapsed Indolent or Mantle Cell Non-Hodgkin's Lymphoma (NHL)	NCT00076349	Non-Hodgkin's L...	bendamustine an...	18 Years -	Teva Branded Pharmaceutical Products R&D, Inc.
Bendamustine and Rituximab for the Treatment of Splenic Marginal Zone Lymphoma	NCT02853370	Marginal Zone B...	Bendamustine an...	18 Years - 80 Years	International Extranodal Lymphoma Study Group (IELSG)

Spots Global Cancer Trial Database for bendamustine and rituximab