Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasm, Residual

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Neoplastic Processes

Lymphosarcoma

Follicular Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Obinutuzumab

Bendamustine Hydrochloride

Immunomodulating Agents

Antineoplastic Agents, Alkylating

Alkylating Agents

Antineoplastic Agents, Immunological

Patients with follicular lymphoma treated with obinutuzumab bendamustine \& achieving MRD negativity as well as complete metabolic response on PET-CT at mid-induction would continue obinutuzumab treatment while omitting bendamustin after 4 cycles.

Bendamustin

Uri Abadi, MD

Follicular lymphoma (FL) is a chronic indolent malignancy, where treatment with 6 cycles of bendamustine obinutuzumab (BO) is highly effective but at a cost of increased adverse events.

Tumor specific DNA can be traced in blood and bone marrow of follicular lymphoma patients even after therapy, and when detected after lymphoma treatment it is referred to as minimal residual disease (MRD).

MRD elimination after effective lymphoma treatment is a marker for deep response and correlates with prolonged remission.

In this study we aim to omit chemotherapy after 4 cycles of treatment in patients achieving MRD elimination after 3 months of therapy, as well as complete metabolic response on positron emission computed tomography (PET-CT), hoping to preserve treatment effectiveness while reducing adverse events.

Follicular lymphoma (FL) is the second most common type of non-Hodgkin's lymphoma, with an estimated incidence of 3.18 cases per 100000 people a year in the United States The disease is characterized by an indolent behavior, where often treatment is unnecessary at diagnosis, and a "watch \& wait" approach is the standard of care for asymptomatic patients. FL is also a highly responsive disease for immuno-chemotherapeutic combinations, although most patients will eventually relapse. Since the disease is incurable \& indolent in nature, the therapeutic strategy should aim for disease control, while using treatments with high safety profile in order to minimize the chance for life threatening adverse events.

Therapy with rituximab cyclophosphamide, doxorubicin, vincristine \& prednisone (R-CHOP) combination \& subsequent rituximab maintenance therapy for 24 months shows excellent results with a median progression free survival (PFS) of above a decade.

The more recent GALLIUM trial has shown that combining the monoclonal antibody obinutuzumab with chemotherapy is even more efficacious compared to rituximab combinations. When different combinations were examined in this trial the best results were achieved with the bendamustine-obinutuzumab (BO) combination with 3 year PFS of 84%. Unfortunately the trial also revealed a downside for this effective combination with higher rate of fatal adverse events among patients receiving 6 cycles of bendamustine combinations.

In patients with acute leukemia evaluation for minimal residual disease (MRD) is a routine procedure, and the nature \& length of treatment are guided by MRD status at different time points during therapy.

Among FL patients treated with obinutuzumab-chemotherapy combinations, it has been shown that after 3 cycles of treatment about 90% of patients were MRD negative. In addition MRD negativity at the end of induction in either peripheral blood or bone marrow was found to be associated with improved outcomes in patients with 1st line treatment for FL as well as in the relapsed setting.

These findings raise the possibility for an MRD based treatment approach, where the duration of chemotherapy could be guided by MRD status at mid-induction. Eliminating chemotherapy while continuing immunotherapy after achievement of MRD negativity \& complete metabolic remission on PET-CT at mid-induction could reduce treatment toxicity, while potentially preserving efficacy.

Prospective multicenter, single arm, phase II study

Adjustment of Chemotherapy Duration in Follicular Lymphoma According to Minimal Residual Disease Status

Adjustment of Chemotherapy Duration in Follicular Lymphoma Patients According to Peripheral Blood or Bone Marrow Minimal Residual Disease Status

Progression-free survival is defined as the time from randomization to the earliest event of progression, relapse, or death from any cause. progression-free survival, is assessed by the investigator.

POD24 is defined as disease progression or death due to disease progression occurring within 24 months after treatment initiation, as assessed by the investigator.

Overall survival is defined as the time from study initiation to death from any cause.

MRD will be assessed at mid-induction, end of induction and subsequently every 6 months.

The proportion of various adverse events will be assessed as documented by the investigator.

Rabin Medical Center

Tel-Aviv Sourasky Medical Center

Assuta Ashdod Hospital

Ziv Medical Center

Meir Medical Center

Antirheumatic Agents

Anti-Inflammatory Agents

Anti-Infective Agents

Antibodies

Antibodies, Monoclonal

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Prednisone

Rituximab

Vincristine

Lenalidomide

Immunoglobulins

Compound 21

Immunosuppressive Agents

Immunologic Factors

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Angiogenesis Inhibitors

Growth Inhibitors

Tubulin Modulators

Antimitotic Agents

5 mg (step-up dosing) Day 1 of C1 45 mg Day 8 and Day 15 of C1, 45 mg Day 1 from C2 to C12, 45 mg Day 1 from C13 to C21

Mosunetuzumab

when associated to CHOP IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C20

when associated to CHOP 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C18

1.4 mg/m2 (cap cf. below)$ Day 1 from C1 to C6

Vincristin

when associated to bendamustin IV 375mg/m² SC 1400 mg allowed from C2 Day 1 of C1 Day 1 from C2 to C6 Day 1 from C7 to C18

when associated to bendamustin 1000 mg Day 1, Day 8, Day 15 of C1 Day 1 from C2 to C8 Day 1 from C9 to C20

Julie ASSEMAT

Marion TAYOL

Sylvia SNAUWAERT, Pr

Marie MAEREVOET, MD

Eric VAN DEN NESTE, Pr

Delphine PRANGER, MD

Ciel DE WRIENDT, MD

Christophe BONNET, Pr

Gaetan VANSTRAELEN, MD

Gilles CROCHET, MD

Hacène ZERAZHI, MD

Sophie BERNARD, MD

Adrien CHAUCHET, MD

Fontanet BIJOU, MD

Martin GAUTHIER, MD

Arthur DONY, MD

Romain GUIEZE, Pr

François LEMONNIER, MD

Amandine DURAND, MD

Nadine MORINEAU, MD

Sylvain CARRAS, MD

Sandy AMORIM, MD

Franck MORSCHHAUSER, Pr

Julie ABRAHAM, MD

Gabriel BRISOU, MD

Guillaume CARTRON, Pr

Bernard DRENOU, MD

Thomas GASTINNE, MD

Gaëlle OLIVIER, MD

Catherine THIEBLEMONT, Pr

François-Xavier GROS, MD

Emmanuel BACHY, Pr

Mohammed BOUDERBALA, MD

Stéphanie GUIDEZ, MD

Hannah MOATTI, MD

Eric DUROT, MD

Roch HOUOT, Pr

Fabrice JARDIN, Pr

Clémentine SARKOZY, MD

Ludovic FOUILLET, MD

Luc-Matthieu FORNECKER, Pr

Loïc YSEBAERT, MD

Laurianne DRIEU LA ROCHELLE, MD

Sabine TRICOT, MD

Pierre FEUGIER, Pr

Antoine BONNET, MD

Vincent RIBRAG, MD

Stephanie MAYER, MD

Christian BUSKE, Pr

Maria GOMES DA SILVA, Pr

Alejandro MARTIN GARCIA-SANCHO, MD

Franck MORSCHHAUSER

Christian BUSKE

This study is a phase III, randomized, open-label, international, multicenter, interventional trial, designed to compare the efficacy and safety of mosunetuzumab in combination with lenalidomide versus anti-CD20 monoclonal antibody (mAb) plus chemotherapy in patients with previously untreated FLIPI 2-5 follicular lymphoma.

This study is a phase III, randomized, open-label, international, multicenter, interventional trial, designed to compare the efficacy and safety of mosunetuzumab in combination with lenalidomide versus anti-CD20 monoclonal antibody (mAb) plus chemotherapy in patients with previously untreated Follicular Lymphoma International Prognostic Index (FLIPI) 2-5 follicular lymphoma This study is composed of a screening period (up to 6 weeks before randomization, i.e., 42 days), a treatment period (30 months i.e., 125w), a safety follow-up period (90 days i.e., 3 months), and a survival follow-up period (up to 7 years after the last randomized patient). The enrollment will last approximately 34 months. The total duration of the study will be therefore approximately 10 years.

Once a patient provides written consent, they may enter the screening phase, with a duration up to 6 weeks prior to randomization and initiation of treatment.

Upon completion of the required assessments in the screening phase, and fulfillment of the eligibility criteria, patients will be randomized. Investigators will be requested to indicate their treatment choice among permitted immuno-chemotherapy regimens just before randomization.

The treatment period for each patient starts with the first intake. The patients will receive protocol-specified treatments until:

* inability to achieve a response at the end of induction phase (at M12 evaluation for experimental arm, and at M6 evaluation for control arms),
* relapse or progression of the disease,
* withdrawal of consent,
* or unacceptable toxicity

In the experimental arm, patients will be treated for 1 cycle of 3 weeks for mosunetuzumab and then 11 cycles of 4 weeks for mosunetuzumab and lenalidomide (47 weeks, around 11 months) during the induction phase, and for a maximum of 9 additional cycles of 8 weeks during the maintenance phase (72 weeks, around 17 months), up to around 125 weeks (30 months). Patients should start the maintenance phase 7 to 8 weeks after the start of last induction cycle (C12).

In the control arm, patients will be treated for 8 or 6 cycles of 3 or 4 weeks for anti-CD20 mAb +cyclophosphamide-doxorubicine-vincristine-prednisone (CHOP) or anti-CD20 mAb + Bendamustine, respectively, depending on the assigned arm (24 weeks, around 5 months) during the induction phase, and for a maximum of 12 additional cycles of 8 weeks during the maintenance phase (96 weeks, around 22 months), up to around 125 weeks (30 months). Patients should start the maintenance phase, 6 to 7 or 7 to 8 weeks after the start of last induction cycle (C8 or C6).

The option to cross-over from the control arm to the experimental arm is not allowed.

All randomized patients will be followed for progression-free survival and overall survival using the same schedule. Patients will be followed up from End of treatment evaluation every 3 months during the first two years, then every 6 months during the next 3 years, then yearly until the end of study.

The end of study will occur when all randomized patients have been followed-up for survival for at least 7 years (or discontinued study early).

Study of Mosunetuzumab Plus Lenalidomide Compared to Anti-CD20 Anti-body + Chemotherapy in Follicular Lymphoma FLIPI2-5

A Phase III Randomized, Open-label, International, Multicenter Study Evaluating the Efficacy and Safety of Mosunetuzumab Plus Lenalidomide in Comparison to Anti-CD20 Monoclonal Antibody Plus Chemotherapy in Subjects With Previously Untreated FLIPI 2-5 Follicular Lymphoma

time from randomization to the date of first documented disease progression/relapse or death from any cause, by Lugano 2014

by Lugano 2014, assessed by investigator and IRC

rate of progression of disease (POD) within 2 years of first line therapy

time between randomization and date of first documented disease progression/relapse, initiation of a new anti-lymphoma treatment or death from any cause

time between randomization and date of first documented administration of any new anti-lymphoma treatment

defined for patients with a best overall response of CMR or PMR determined by Lugano 2014, defined as the time of 1st occurrence of CMR or PMR to disease progression/relapse or death from any cause

for patients with a best overall response of CMR determined by Lugano 2014, define as the time of first occurrence of CMR to disease progression/relapse or death from any cause

time from randomization to death from any cause

EORTC QLQ-C30 quality of life questionnaire

FACTLym LYMS quality of life questionnaire

Lymphoma Study Association

Swiss Group for Clinical Cancer Research

Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

The Lymphoma Academic Research Organisation

Bortezomib

Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.

Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

rituximab

bortezomib

lenalidomide

Andrew M. Evens, DO, MS

RATIONALE: Drugs used in chemotherapy, such as bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. It is not yet known whether giving bendamustine hydrochloride and rituximab together alone is more effective than giving bendamustine hydrochloride and rituximab together with bortezomib or lenalidomide in treating follicular lymphoma.

PURPOSE: This randomized phase II trial is studying giving bendamustine hydrochloride and rituximab together with or without bortezomib followed by rituximab with or without lenalidomide to see how well they work in treating patients with high-risk stage II, stage III, or stage IV follicular lymphoma.

OBJECTIVES:

Primary

* To compare the complete remission rate in patients with high-risk follicular lymphoma receiving induction therapy comprising bendamustine hydrochloride and rituximab with vs without bortezomib.
* To compare the 1-year post-induction disease-free survival rate in patients receiving continuation therapy comprising rituximab with vs without lenalidomide.

Secondary

* To determine the 3-year progression-free survival and the 5-year overall survival of these patients.
* To evaluate patient-reported outcomes at baseline and during treatment to determine differences in symptom palliation, treatment-related symptoms, and overall health-related quality of life.
* To examine the association between baseline Follicular Lymphoma International Prognostic Index (FLIPI) information and outcome of these patients.
* To examine the association between baseline and end-of-treatment patient comorbidities assessed by the Cumulative Illness Rating Scale (CIRS) and outcome.
* To create an image and tissue bank including serial PET/CT scans, diagnostic paraffin-embedded tissue, germline DNA, and serial blood and bone marrow samples sufficient to support proposed and future studies of tumor and host characteristics that may predict for clinical outcome, including treatment arm effects, and enhance existing prognostic indices. (exploratory)
* To evaluate the rate of peripheral neuropathy associated with subcutaneous and intravenous bortezomib.

OUTLINE: Patients are stratified according to FLIPI-1score (0-2 vs 3 vs 4-5) and Groupe d'Etude des Lymphomes Folliculaires (GELF) tumor burden (low vs high). Patients are randomized to 1 of 3 treatment arms.

* Arm A then Arm D

  * Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
  * Arm D (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.
* Arm B then Arm E

  * Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
  * Arm E (continuation): Beginning 4 weeks after the completion of induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.
* Arm C then Arm F

  * Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.
  * Arm F (continuation): Immediately after completing induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Quality of life (including fatigue, neurotoxicity, anxiety, and depression) is assessed by questionnaire at baseline and periodically during study therapy.

Blood, bone marrow, and tissue samples may be collected periodically for correlative studies and for a repository.

After completion of study therapy, patients are followed up periodically for 15 years.

Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma

A 3-Arm Randomized Phase II Trial of Bendamustine-Rituximab (BR) Followed by Rituximab vs Bortezomib-BR (BVR) Followed by Rituximab vs BR Followed by Lenalidomide/Rituximab in High Risk Follicular Lymphoma

Individual participant data may be made available upon request as per the ECOG-ACRIN Data Sharing Policy.

Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.

This analysis was conducted among 222 evaluable patients for the primary analysis. The purpose of this analysis is to compare the complete remission rate of rituximab + bendamustine vs. bortezomib + rituximab + bendamustine as induction therapy, therefore, the proportion of patients with complete remission was compared between Arm B (bortezomib + rituximab + bendamustine) and Arms A and C combined (rituximab + bendamustine).

1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.

The purpose of this analysis is to compare the 1-year post-induction disease-free survival (DFS) rate with rituximab plus lenalidomide to rituximab alone as continuation therapy following induction treatment of bendamustine+rituximab, therefore, patients with induction treatment of bendamustine + rituximab + bortezomib were not included in this analysis.

Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. 3-year progression-free survival rate is the proportion of patients who were progression-free and alive at 3 years estimated using the method of Kaplan-Meier.

Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, \>=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.

Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.

Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.

This analysis was conducted among 222 evaluable patients. The proportion of patients with complete remission was compared between patients with Follicular Lymphoma International Prognostic Index (FLIPI) of 3-5 and patients with FLIPI of 0-2/unknown.

The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.

This analysis was conducted among 203 evaluable patients in the continuation treatment portion of the study. The 1-year post induction disease-free survival rate was compared between patients with FLIPI of 3-5 and patients with FLIPI of 0-2/unknown.

The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, \>=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.

The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.

The FLIPI was developed in order to predict prognosis of patients with newly diagnosed follicular lymphoma (FL). The five FLIPI risk factors were: age \> 60 years, Ann Arbor stage III-IV, hemoglobin level \< 12 gm/dL, \>4 nodal areas, and serum LDH level above normal. The FLIPI score was calculated by summing the number of risk factors. The higher the FLIPI score, the worse the prognosis.

Complete remission is defined as complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present prior to therapy.

This analysis was conducted among 250 evaluable patients with Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients with complete remission was compared between patients with CIRS \<10 and patients with CIRS \>=10. Higher CIRS scores indicate higher severity with max score of 56 points.

1-year post induction disease-free survival rate is defined as the proportion of patients achieving complete remission during induction treatment and are alive and maintaining complete remission at 1 year after induction completion.

This analysis was conducted among 250 evaluable patients with Cumulative Illness Rating Scale (CIRS) data available. The proportion of patients disease-free and alive at 1 year post induction treatment was compared between patients with CIRS \<10 and patients with CIRS \>=10. Higher CIRS scores indicate higher severity with max score of 56 points.

Progression-free survival is defined as the time from registration of induction treatment to progression, relapse or death, whichever occurs first. Patients alive without documented progression are censored at last disease assessment. 3-year progression-free survival rate is the proportion of patients who were progression-free and alive at 3 years estimated using the method of Kaplan-Meier.

Progression/relapse is defined as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, \>=50% increase from nadir in the SPD of any previously involved nodes or extranodal masses or the size of other lesions, or \>=50% increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in its short axis.

The 3-year progression-free survival rate is reported by Cumulative Illness Rating Scale (CIRS) score (\<10 vs. \>=10). Higher CIRS scores indicate higher severity with max score of 56 points.

Overall survival is defined as the time from randomization to death or date last known alive. 5-year overall survival rate is the proportion of patients who were alive at 5 years estimated using the method of Kaplan-Meier.

The 5-year overall survival rate is reported by Cumulative Illness Rating Scale (CIRS) score (\<10 vs. \>=10). Higher CIRS scores indicate higher severity with max score of 56 points.

Peripheral neuropathy was assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Proportion of patients with grade 3 or higher peripheral neuropathy was compared between patients with subcutaneous bortezomib and patients with intravenous bortezomib.

The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life.

The Functional Assessment of Cancer Therapy - General (FACT-G) is a 27-item questionnaire that has four areas of measurements (physical well-being, social/family well-being, emotional well-being and functional well-being) with a scale of 0-4. The FACT-G total score ranges between 0 and 108. The higher the score, the better the quality of life.

FACT-G total score at cycle 3 is considered as mid-treatment score. If FACT-G total score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.

The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life.

The Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) is a 15-item questionnaire that evaluates disease-related symptoms and concerns specific to lymphoma with a scale of 0-4. The FACT-Lym subscale score ranges between 0 and 60. The higher the score, the better the quality of life.

FACT-Lym subscale score at cycle 3 is considered as mid-treatment score. If FACT-Lym subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.

The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life.

The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) is comprised of 13 items that assess fatigue and its impact with a scale of 0-4. The FACIT-Fatigue subscale score ranges between 0 and 52. The higher the score, the better the quality of life.

FACIT-Fatigue subscale score at cycle 3 is considered as mid-treatment score. If FACIT-Fatigue subscale score at cycle 3 is not available, the score at cycle 4 will be used as the mid-treatment score.

The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT-GOG-NTX) subscale is comprised of 11 items that assess neurotoxicity with a scale of 0-4. The FACT-GOG-NTX subscale score ranges between 0 and 44. The higher the score, the better the quality of life.

National Cancer Institute (NCI)

ECOG-ACRIN Cancer Research Group

Serious Adverse Events include post-baseline adverse events of grade 3 and higher that are definitely, probably or possibly related to protocol treatment based on the case report forms (CRFs).

Only patients who started protocol therapy are included in the analysis of adverse events. All registered patients are included in the analysis of all-cause mortality.

Deaths were counted in Step 1 (Arms A, B and C) for patients who did not registered to Step 2 continuation treatment.

Arm A (induction): Patients receive rituximab intravenously (IV) on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Arm A

Arm B (induction): Patients receive rituximab IV on day 1; bortezomib IV on days 1, 4, 8, and 11; and bendamustine hydrochloride IV over 1 hour on days 1 and 4. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Arm B

Arm C (induction): Patients receive rituximab IV on day 1 and bendamustine hydrochloride IV over 1 hour on days 1 and 2. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

Arm C

Arm D (continuation after Arm A): Beginning 4 weeks after the completion of Arm A induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Arm D

Arm E (continuation after Arm B): Beginning 4 weeks after the completion of Arm B induction therapy, patients who have stable disease or better at time of post-induction restaging receive rituximab as in arm D.

Arm E

Arm F (continuation after Arm C): Immediately after completing Arm C induction therapy, patients who have stable disease or better at time of post-induction restaging receive oral lenalidomide on days 1-21. Treatment repeats every 4 weeks for 13 courses in the absence of disease progression or unacceptable toxicity. Beginning 4 weeks after the completion of induction therapy, these patients receive rituximab IV on day 1. Treatment repeats every 8 weeks for 2 years in the absence of disease progression or unacceptable toxicity.

Arm F

Arm A Then Arm D (Induction With Bendamustine + Rituximab; Continuation With Rituximab)

Arm B Then Arm E (Induction With Bendamustine + Rituximab + Bortezomib; Continuation With Rituximab)

Arm C Then Arm F (Induction With Bendamustine+Rituximab; Continuation With Lenalidomide + Rituximab)

Total

Eligible and treated patients are included in this analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Adjustment of Chemotherapy Duration in Follicular Lymphoma According to Minimal Residual Disease Status	NCT04934930	Follicular Lymp...	Bendamustin Obinutuzumab	18 Years -	Meir Medical Center
Study of Mosunetuzumab Plus Lenalidomide Compared to Anti-CD20 Anti-body + Chemotherapy in Follicular Lymphoma FLIPI2-5	NCT06284122	Follicular Lymp...	Mosunetuzumab Lenalidomide Rituximab Obinutuzumab Cyclophosphamid... Doxorubicin Vincristin Prednisone Rituximab Obinutuzumab Bendamustin	18 Years -	The Lymphoma Academic Research Organisation
Bendamustine Hydrochloride and Rituximab With or Without Bortezomib Followed by Rituximab With or Without Lenalidomide in Treating Patients With High-Risk Stage II, Stage III, or Stage IV Follicular Lymphoma	NCT01216683	Lymphoma	rituximab Bendamustin bortezomib lenalidomide	18 Years -	Eastern Cooperative Oncology Group
Tumor Registry of Lymphatic Neoplasia	NCT00889798	Non-Hodgkin's L... Chronic Lymphoc... Multiple Myelom...		18 Years -	iOMEDICO AG
Bendamustin Hydrochloride in Patients With Soft Tissue Sarcoma (STS)	NCT00204620	Sarcoma, Soft T...	Bendamustin	18 Years -	University Hospital Tuebingen
Study of Mosunetuzumab Plus Lenalidomide Compared to Anti-CD20 Anti-body + Chemotherapy in Follicular Lymphoma FLIPI2-5	NCT06284122	Follicular Lymp...	Mosunetuzumab Lenalidomide Rituximab Obinutuzumab Cyclophosphamid... Doxorubicin Vincristin Prednisone Rituximab Obinutuzumab Bendamustin	18 Years -	The Lymphoma Academic Research Organisation
A Study of the Zanubrutinib Given in Combination With Bendamustine and Rituximab in (Elderly or TP53 Alterations or Chemotherapy Intolerance) Patients With Newly Diagnosed Mantle Cell Lymphoma	NCT06136351	Lymphoma, Mantl...	Zanubrutinib Rituximab Bendamustin	18 Years -	Ruijin Hospital
Tumor Registry of Lymphatic Neoplasia	NCT00889798	Non-Hodgkin's L... Chronic Lymphoc... Multiple Myelom...		18 Years -	iOMEDICO AG

Spots Global Cancer Trial Database for bendamustin

Every month we try and update this database with for bendamustin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bendamustin

Every month we try and update this database with for bendamustin cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bendamustin cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.