Bendamustine in Combination With Rituximab as a First-line Therapy Followed by Maintenance Therapy With Rituximab in Patients With Follicular Lymphoma (BRiF)

National Research Center for Hematology, Russia

Status and phase

Unknown

Phase 3

Conditions

Follicular Lymphoma

Treatments

Drug: Rituximab, bendamustine

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT02423837

FL-RUS-2013

Details and patient eligibility

About

To evaluate the efficacy of bendamustine in combination with rituximab as first line in patients with follicular lymphoma, 1-3A cytological type.
To evaluate the safety, tolerability and feasibility of bendamustine in combination with rituximab as 1st line in patients with follicular lymphoma, 1-3A cytological type.
To evaluate the impact of the regimen modification (bendamustine dose modification and/or extension of inter-cycle interval) into duration of complete and partial responses.
To evaluate estimated treatment duration, reasons of treatment withdrawal.
To evaluate the possibility of unification and standardization of therapy protocol BR (rituximab 375 mg/m2 on day 1 and bendamustine 90 mg/m2 on days 1-2).
To evaluate factors affecting overall and progression-free survival.

Full description

Protocol involves 6 courses of rituximab and bendamustine with 26 days interval between each course (one cycle continues 28 days). Control examination will be performed every two courses (28, 56, 84 days of treatment) and will include (physical examination, monitoring of clinical blood tests, biochemical blood tests, computed tomography, ultrasonography, in patients with gastrointestinal tract involvement - fibrogastroduodenoscopy and colonoscopy). Efficacy of therapeutic impact will be estimated as rates of complete remission, partial remission, stable disease or progression based on tumor size reduction comparing with pretreatment data and evaluated using computed tomography and expressed as a percentage. Patients with partial or complete remission or stable disease after 2 courses continue treatment. Patients with tumor progression excluded from issue. Patients which achieved a complete remission after 2 courses may end treatment after 4 courses.

Safety, tolerability and feasibility which implies hematologic and non-hematologic toxicity will be estimated using data of physical examination, monitoring of clinical blood tests, biochemical blood tests and bone marrow analyses (cytological, morphological and genetic tests).

Enrollment

200 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with the diagnosis of follicular lymphoma confirmed by immunohistochemistry (IHC) analysis in the reference laboratory
Written informed consent for the use of personal data approved by Independent Ethic Committee
Men and women patients, 18-75 years old
ECOG performance status ≤ 3
No previous treatment with chemotherapy and/or radiation therapy of follicular lymphoma

Exclusion criteria

The patient is participating in any clinical trials and/or receiving the experimental treatment.
Transformation of follicular lymphoma to large cell lymphoma (for example, follicular lymphoma IIIB graduation, diffuse large B-cell lymphoma).
Central nervous system involvement.
The presence of a second malignancy within the last 5 years prior to the inclusion into the study except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or prostate cancer.
Clinically significant cardiovascular or cerebro-vascular disease in the past 6 months, such as acute myocardial infarction, unstable angina, significant ventricular arrhythmia, severe heart failure (NYNA class IV), stroke, or uncontrolled hypertension.
Renal impairment (serum creatinine > 150 umol/L), except lymphoid infiltration of kidneys and tumor lysis syndrome.
Liver failure (except leukemic/lymphoid organ infiltration), acute hepatitis (serum bilirubin > 2 x ULN, the activity of ALT and AST > 4 x ULN, prothrombin index < than 50%).
Uncontrolled diabetes mellitus (serum glucose > 15 mmol/L)
Sepsis (septicopyemic focuses, hemodynamic instability, inefficiency of antibacterial therapy) or acute infectious diseases.
HIV, hepatitis B and C (including the absence of the Hbc and Hbs antibodies).
Life-threatening bleeding, except of bleeding from the gastrointestinal tract caused by neoplastic process.
Severe mental disorders (schizophrenia, major depressive syndrome and other productive symptoms).
Physical failure requiring constant care, cachexia (total protein < 35 g/L).
Known hypersensitivity to rituximab components.
Known hypersensitivity to bendamustine components.
Pregnant or currently breast-feeding woman
Neutrophils count < 1500/mm3 and/or platelets count < 75000/mm3.
Surgery prior 15 days before therapy initiation.
In case of serious infectious complications relief, uncontrolled diabetes, hemorrhagic syndrome, hypertension patient may be included into the study