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NCT00369707

Trial of VELCADE and Rituxan as Front-line Tx for Low-grade NHL

Completed Phase 2 Results posted Last updated 6 September 2019
What this trial tests

Phase 2 trial testing Rituximab in Non-Hodgkin's Lymphoma in 42 participants. Completed in 10 October 2014.

Timeline
9 August 2006
Primary endpoint
22 May 2012
10 October 2014

Quick facts

Lead sponsorNorthwestern University
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment42
Start date9 August 2006
Primary completion22 May 2012
Estimated completion10 October 2014
Sites4 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Northwestern University

Who can join

18 and older, any sex, with Non-Hodgkin's Lymphoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (Complete Response and Partial Response) After Three Inductions Cycles of Treatment. Primary · At baseline and at the completion of 3 cycles of treatment where 1 cycle equals 35 days.

The primary objective of this study is to assess the overall response rate. Overall response rate at this time point will be defined as complete response \[CR\] plus partial response \[PR\]) after 3 cycles of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL. Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase \[LDH\]) definit

GroupValue95% CI
Bortezomib and Rituximab71
Overall Response Rate After 1 Course of Induction Therapy Secondary · At baseline and at the completion of cycle 1 (1 cycle =35 days)

Overall response rate (ORR) after 1 cycle of bortezomib/rituximab induction therapy. Overall response rate at this time point will be defined as complete response \[CR\] plus partial response \[PR\]) after 1 cycle of bortezomib/rituximab induction therapy for patients with previously untreated low-grade, B-cell NHL. Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g., lactate dehydrogenase \[LDH\]

GroupValue95% CI
Bortezomib and Rituximab33
Overall Response Rate After Completion of Maintenance Therapy Secondary · At baseline and every 2 months during treatment of up to 3 cycles of induction (1 cycle =35days) and 4 cycles of maintenance (1 cycle =2 months) for up to 12 months.

Overall response rate at completion of bortezomib/rituximab maintenance therapy. Overall response rate at this time point will be defined as complete response \[CR\] plus partial response \[PR\]) after 3 cycles of bortezomib/rituximab induction therapy and up to 4 cycles of maintenance for patients with previously untreated low-grade, B-cell NHL. Complete response requires complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy, and normalization of those biochemical abnormalities (e.g.

GroupValue95% CI
Bortezomib and Rituximab71
Number of Patients That Experience Adverse Events With Bortezomib/Rituximab Combination Treatment Secondary · Day 1 of each cycle and at the completion of cycles 1 and 3, during treatment up to 12 months

Assess the safety and tolerance of bortezomib/rituximab as induction and maintenance therapy. Data will be collected for grade 3 and grade 4 adverse events experienced by patients that are determined to be at least possibly related to at least one study drug. Toxicity data for bortezomib/rituximab will be collected on day 1 of every cycle (1 cycle = 35 days) for up to 7 cycles during treatment according to the National Cancer Institute's Common Toxicity Criteria for adverse events version 3.0 (CTCAE v3.0). In general adverse events (AEs) will be graded according to the following: Grade 1 Mild

Neutropenia
GroupValue95% CI
Bortezomib and Rituximab2
Fever
GroupValue95% CI
Bortezomib and Rituximab2
Infection
GroupValue95% CI
Bortezomib and Rituximab2
Infusion reaction (rituximab)
GroupValue95% CI
Bortezomib and Rituximab2
Cardiac
GroupValue95% CI
Bortezomib and Rituximab2
Fatigue
GroupValue95% CI
Bortezomib and Rituximab2
Throbocytopenia
GroupValue95% CI
Bortezomib and Rituximab1
Diarrhea
GroupValue95% CI
Bortezomib and Rituximab1
Correlation of Tumor Burden Secondary · At the start of treatment and at Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS and OS for all patients is reported at 4 years.

Correlation of tumor burden according to Groupe D'Etude des Lymphomes Follicularies (GELF) with recently developed Follicular Lymphoma International Prognostic Index (FLIPI) prognostic index. All patients enrolled in the study were required to have high tumor burden (HTB) as defined by GELF, where HTB is defined as representing higher risk disease and poorer outcomes than low tumor burden (LTB). Patients were put into low risk or high risk FLIPI groups. Low risk group with a score of 0-2 and high risk group with a score of 3-5. A FLIPI score of 0 to 1 = "low risk" with a 10 year overall survi

4 year PFS high risk FLIPI
GroupValue95% CI
Bortezomib and Rituximab26
4 year PFS low risk FLIPI
GroupValue95% CI
Bortezomib and Rituximab60
4 year OS high risk FLIPI
GroupValue95% CI
Bortezomib and Rituximab81
4 year OS low risk FLIPI
GroupValue95% CI
Bortezomib and Rituximab92
Percentage of Patients With Treatment Failure Secondary · Median follow up for all patients was 50 months and on intent to treat, TTF rate for all patients is reported at 4 years.

Time to Treatment Failure (TTF) rate measured, from the time of first treatment to disease progression, relapse, second tumor, death from any cause, treatment toxicity requiring termination from the study, or for any reason treatment is discontinued permanently.

GroupValue95% CI
Bortezomib and Rituximab26
Progression Free Survival (PFS) Rate Secondary · Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, PFS for all patients is reported at 4 years.

Progression Free Survival is measured from the time of first induction infusion to disease progression, relapse, second tumor, or death from any cause. Progressive disease (PD) requires the following: 1. Appearance of any new lesion or increase by \> 50% in the size of previously involved sites. 2. Increase of \> 50% in the SPD from nadir measurement of all involved dominant lymph nodes and liver nodules and spleen nodules or unequivocal progression in any non measurable disease or nondominant site. 3. \> 50% increase in greatest diameter of any previously identified node greater than 1 cm i

GroupValue95% CI
Bortezomib and Rituximab44
Overall Survival Rate Secondary · Median follow up for all patients was 50 months (range 12-78 months) and on intent to treat, OS rate for all patients is reported at 4 years.

Overall survival (OS) will be measured from the time of first treatment to death from any cause.

GroupValue95% CI
Bortezomib and Rituximab87

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse events were collected for the whole study over a 6 year and 4 month period. On average adverse event information for each patient was collected during patients treatment, for a maximum of 12 months.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Bortezomib and Rituximab
Serious: 7/42 (17%)
Deaths: 6/42

Serious adverse events (8 terms)

ReactionSystemBortezomib and Rituximab
Fever with normal ANCGeneral disorders
Diastolic heart failureCardiac disorders
Congestive Heart Failure exacerbationCardiac disorders
Anal squamous cell carcinomaCongenital, familial and genetic disorders
DehydrationGastrointestinal disorders
PneumoniaInfections and infestations
Lumbar disk painMusculoskeletal and connective tissue disorders
Fainting episode (Syncope)Nervous system disorders
Other adverse events (55 terms — click to expand)

ReactionSystemBortezomib and Rituximab
NauseaGastrointestinal disorders
LymphopeniaBlood and lymphatic system disorders
FatigueGeneral disorders
DiarrheaGastrointestinal disorders
Leukocytes (total white blood cells)Blood and lymphatic system disorders
Hemoglobin (anemia)Blood and lymphatic system disorders
Glucose, serum highMetabolism and nutrition disorders
Allergic reaction/hypersensitivityImmune system disorders
Platelets (thrombocytopenia)Blood and lymphatic system disorders
Rash/desquamationSkin and subcutaneous tissue disorders
Allergic rhinitisImmune system disorders
Neutrophils (neutropenia)Blood and lymphatic system disorders
VomitingGastrointestinal disorders
Sensory neuropathyNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
FeverGeneral disorders
Bilirubin, serum highMetabolism and nutrition disorders
SweatingGeneral disorders
Weight lossGeneral disorders
Pruritus/itchingSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
AnorexiaGastrointestinal disorders
TransaminaseMetabolism and nutrition disorders
Glucose, serum lowMetabolism and nutrition disorders
Potassium, serum lowMetabolism and nutrition disorders
General pain NOSGeneral disorders
Shortness of breath (dyspnea)Respiratory, thoracic and mediastinal disorders
Flu like syndromeGeneral disorders
InsomniaGeneral disorders
Edema in limbsBlood and lymphatic system disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders
Albumin, serum lowMetabolism and nutrition disorders
Calcium, serum lowMetabolism and nutrition disorders
Pain in abdomenGastrointestinal disorders
Mucositis/stomatitisGastrointestinal disorders
Eye infectionInfections and infestations
EdemaBlood and lymphatic system disorders
ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders
Lactic acid dehydrogenase (LDH)Metabolism and nutrition disorders

Most-reported serious reactions: Fever with normal ANC, Diastolic heart failure, Congestive Heart Failure exacerbation, Anal squamous cell carcinoma, Dehydration, Pneumonia, Lumbar disk pain, Fainting episode (Syncope).

Data from ClinicalTrials.gov NCT00369707 adverse events section.

Sponsor's own description

Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. 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. Giving bortezomib together with rituximab may kill more cancer cells. This phase II trial is studying how well giving bortezomib together with rituximab works as first-line therapy in treating patients with low-grade B-cell non-Hodgkin's lymphoma.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Frontline bortezomib and rituximab for the treatment of newly diagnosed high tumour burden indolent non-Hodgkin lymphoma: a multicentre phase II study.
    Evens AM, Smith MR, Lossos IS, Helenowski I, et al · · 2014 · cited 14× · PMID 24761968 · DOI 10.1111/bjh.12915

Verify or expand the search:

Other trials of Rituximab

Trials testing the same drug.

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Other Northwestern University trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00369707.

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