NCT01596621

A Study of Bendamustine in the Treatment of Chinese Participants With Indolent Non-Hodgkin Lymphoma Refractory to Rituximab Treatment

Completed Phase 3 Results posted Last updated 26 May 2023

What this trial tests

Phase 3 trial testing Bendamustine hydrochloride in Non-Hodgkin Lymphoma in 102 participants. Completed in 24 April 2017.

Timeline

6 August 2012

Primary endpoint
18 June 2015

24 April 2017

Quick facts

Lead sponsor	Teva Branded Pharmaceutical Products R&D, Inc.
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	102
Start date	6 August 2012
Primary completion	18 June 2015
Estimated completion	24 April 2017
Sites	27 locations across China

Drugs / interventions tested

• Bendamustine hydrochloride — full drug profile →

Conditions studied

• Non-Hodgkin Lymphoma — all drugs for Non-Hodgkin Lymphoma →

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. — full company profile →

Who can join

18 and older, any sex, with Non-Hodgkin 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 (ORR) (Assessed by Independent Review Committee [IRC]) Primary · From the date of the first administration of bendamustine to the first documentation of disease progression/relapse, new anticancer therapy, or death (regardless of cause), whichever occurred first (up to 2.5 Years)

The ORR was defined as the percentage of participants who achieved a best response of complete response (CR) or partial response (PR) during the study based on the modified International Workshop Response Criteria. CR: disappearance of all evidence of disease; nodal masses regression on normal size on computed tomography (CT); spleen and liver not palpable and nodule disappeared; bone marrow infiltrate cleared on repeat biopsy. PR: Regression of measurable disease and no new sites; nodal masses ≥50% decrease in sum of the product of the diameters (SPD) of up to 6 largest dominant masses and no

Group	Value	95% CI
Bendamustine	73

Duration of Response (DOR) (Assessed by IRC) Secondary · From the date of first documentation of response to the first documentation of disease progression, new anticancer therapy, or death (regardless of cause), whichever occurred first (up to 2.5 Years)

Duration of response was defined as the time from the date of first documentation of response to the first documentation of disease progression, new anticancer therapy, or death (regardless of cause), whichever occurred first for participants with a best response of CR or PR determined by the modified International Workshop Response Criteria. CR: disappearance of all evidence of disease; nodal masses regression on normal size on CT; spleen and liver not palpable and nodule disappeared; bone marrow infiltrate cleared on repeat biopsy. PR: Regression of measurable disease and no new sites; nodal

Group	Value	95% CI
Bendamustine	16.2	9.3 – NA

Progression-Free Survival (Assessed by IRC) Secondary · From the date of the first administration of bendamustine to the first documentation of disease progression/relapse, new anticancer therapy, or death (regardless of cause), whichever occurred first (up to 2.5 Years)

Progression free survival was defined as the time from the date of the first administration of bendamustine to the first documentation of disease progression/relapse, new anticancer therapy, or death (regardless of cause), whichever occurred first for all participants. Disease progression/relapse: appearance of any new lesion or increase by ≥50% of previously involved sites from nadir.

Group	Value	95% CI
Bendamustine	18.6	12.3 – NA

Maximum Observed Plasma Concentration (Cmax) of Bendamustine Secondary · Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1 (each cycle is 21 days)

Group	Value	95% CI
Bendamustine	3909.9	± 2995.83

Time to Reach Cmax (Tmax) of Bendamustine Secondary · Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1 (each cycle is 21 days)

Group	Value	95% CI
Bendamustine	1.30	0.58 – 1.97

Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Drug Concentration (AUC0-t) of Bendamustine Secondary · Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1 (each cycle is 21 days)

Group	Value	95% CI
Bendamustine	5660.7	± 3932.45

Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) of Bendamustine Secondary · Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1 (each cycle is 21 days)

Group	Value	95% CI
Bendamustine	6278.7	± 4724.82

Rate Constant for Elimination (λz) of Bendamustine Secondary · Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1 (each cycle is 21 days)

Group	Value	95% CI
Bendamustine	0.4525	± 0.24245

Percentage of the AUC0-∞ Based on Extrapolation (%AUCext) Secondary · Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1 (each cycle is 21 days)

Group	Value	95% CI
Bendamustine	0.01	± 0.004

Half-Life (t½) of Bendamustine Secondary · Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1 (each cycle is 21 days)

Group	Value	95% CI
Bendamustine	1.83	± 0.684

Number of Participants With Adverse Events (AEs) Secondary · From first administration of bendamustine through 30 days after the last administration (up to 2.5 Years)

An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.

Group	Value	95% CI
Bendamustine	101

World Health Organization (WHO) Performance Status Secondary · At the end of treatment (up to 2.5 years)

Number of participants with WHO performance status (improved, stayed the same, and deteriorated) at the end of treatment have been reported.

Group	Value	95% CI
Bendamustine	6
Bendamustine	73
Bendamustine	7

Adverse events — posted to ClinicalTrials.gov

Time frame: From first administration of bendamustine through 30 days after the last administration (up to 2.5 Years). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Bendamustine

Serious: 30/102 (29%)

Deaths: —

Serious adverse events (31 terms)

Reaction	System	Bendamustine
Pyrexia	General disorders	—
Pneumonia	Infections and infestations	—
Lung infection	Infections and infestations	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Herpes zoster	Infections and infestations	—
Pancytopenia	Blood and lymphatic system disorders	—
Gastrointestinal infection	Infections and infestations	—
Neutrophil count decreased	Investigations	—
Platelet count decreased	Investigations	—
Bone marrow failure	Blood and lymphatic system disorders	—
Febrile neutropenia	Blood and lymphatic system disorders	—
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Multi-organ failure	General disorders	—
Hepatic failure	Hepatobiliary disorders	—
Hepatitis B	Infections and infestations	—
Herpes virus infection	Infections and infestations	—
Respiratory tract infection	Infections and infestations	—
Upper respiratory tract infection	Infections and infestations	—
Lumbar vertebral fracture	Injury, poisoning and procedural complications	—
Blood bilirubin increased	Investigations	—
White blood cell count decreased	Investigations	—
White blood cell count increased	Investigations	—
Acute myeloid leukaemia	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—

Other adverse events (25 terms — click to expand)

Reaction	System	Bendamustine
White blood cell count decreased	Investigations	—
Neutropenia	Blood and lymphatic system disorders	—
Neutrophil count decreased	Investigations	—
Leukopenia	Blood and lymphatic system disorders	—
Nausea	Gastrointestinal disorders	—
Platelet count decreased	Investigations	—
Vomiting	Gastrointestinal disorders	—
Anaemia	Blood and lymphatic system disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Thrombocytopenia	Blood and lymphatic system disorders	—
Pyrexia	General disorders	—
Lymphocyte count decreased	Investigations	—
Rash	Skin and subcutaneous tissue disorders	—
Asthenia	General disorders	—
Alanine aminotransferase increased	Investigations	—
Infusion site phlebitis	General disorders	—
Lymphopenia	Blood and lymphatic system disorders	—
Upper respiratory tract infection	Infections and infestations	—
Haemoglobin decreased	Investigations	—
Aspartate aminotransferase increased	Investigations	—
Weight decreased	Investigations	—
Pruritus	Skin and subcutaneous tissue disorders	—
Cough	Respiratory, thoracic and mediastinal disorders	—
Fatigue	General disorders	—
Hypokalaemia	Metabolism and nutrition disorders	—

Most-reported serious reactions: Pyrexia, Pneumonia, Lung infection, Respiratory failure, Thrombocytopenia, Herpes zoster, Pancytopenia, Gastrointestinal infection.

Data from ClinicalTrials.gov NCT01596621 adverse events section.

Sponsor's own description

The primary objective of the study is to determine the overall response rate (ORR), which includes complete response (CR) and partial response (PR), to bendamustine treatment in participants with indolent non-Hodgkin lymphoma (NHL) that has progressed after rituximab or a rituximab-containing therapy.

Publications & conference data

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

1. Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study.
   Shi YK, Hong XN, Yang JL, Xu W, et al · · 2021 · cited 3× · PMID 33967195 · DOI 10.1097/cm9.0000000000001463