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

NCT01596621 | Completed Phase 3 Results DMC

• 1 other identifier: C18083/3076
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 27

Brief Summary

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.

Conditions

Non-Hodgkin Lymphoma

Keywords

Bendamustine hydrochloride; CEP-18083; Treanda®; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR) (Assessed by Independent Review Committee [IRC])

  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 increase in size of other nodes; spleen and liver ≥50% decrease in SPD of nodules and no increase in size of liver or spleen.

  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)

Secondary Outcomes (13)

• Duration of Response (DOR) (Assessed by IRC)

  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)

• Progression-Free Survival (Assessed by IRC)

  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)

• Maximum Observed Plasma Concentration (Cmax) of Bendamustine

  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)

• Time to Reach Cmax (Tmax) of Bendamustine

  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)

• Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Drug Concentration (AUC0-t) of Bendamustine

  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)

Study Arms (1)

Bendamustine

EXPERIMENTAL

Participants will receive bendamustine hydrochloride administered at 120 milligrams (mg)/square meter (m\^2) intravenously (IV) as a 60-minute infusion, and not more than 120 minutes, on Days 1 and 2 in each 21-day treatment cycle for 6 planned cycles and up to 8 total cycles.

Drug: Bendamustine hydrochloride

Interventions

Bendamustine hydrochloride DRUG

Bendamustine will be be administered per dose and schedule specified in the arm description.

Also known as: Treanda®

Bendamustine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- The participant has documented relapse from indolent B-cell NHL. Participants with the following subtypes of indolent NHL are eligible for this study: i) small lymphocytic lymphoma (peripheral B cell count \<5000 cells/cubic millimeters \[mm\^3\]) ii) lymphoplasmacytic lymphoma iii) splenic marginal zone B-cell lymphoma (±villous lymphocytes) iv) extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type v) nodal marginal zone lymphoma (±monocytoid B-cells) vi) follicle center lymphoma vii) follicular (grade 1, 2, or 3a) lymphoma
• \- The participant has disease documented to have progressed despite rituximab treatment. The participant's disease is considered to be rituximab refractory if any of the following criteria are met at any time during the participant's treatment history (progression must be documented by computed tomography \[CT\] scan or magnetic resonance imaging \[MRI\] or biopsy) or if a participant has palpable lymph nodes that were well documented in size and, after rituximab treatment, palpable disease remains or comes back \[CT, MRI, or biopsy is preferred and performed whenever possible to document progressive disease (PD)\]: i) rituximab-only regimen: Participants who receive a full course of single-agent rituximab (at least 2 doses of 375 mg/m\^2 \[or a therapeutically-active dose\] weekly) and have no response (do not obtain a PR or better) to treatment or progress after a full regimen of rituximab was given.
• ii) rituximab maintenance therapy or extended schedule: Participants who have a history of a full course of rituximab (at least 2 doses of 375 mg/m\^2 \[or a therapeutically-active dose\] as a single agent \[weekly\] or in combination with chemotherapy \[day 1 of each of 4 cycles\]) and are on a maintenance regimen, and progress before the next scheduled rituximab dose or after completing a maintenance rituximab regimen.
• iii) rituximab-chemotherapy combination regimen: Participants who receive a full course of rituximab (at least 2 doses of 375 mg/m\^2 or a therapeutically-active dose \[on day 1 of each of 2 cycles\]) in combination with chemotherapy and have no response (do not obtain a PR or better) to treatment or progress after the last dose of rituximab in a regimen.
• iv) full rituximab exposure treatment: Participants who have a history of a full course of rituximab treatment (at least 2 doses of 375 mg/m\^2 \[or a therapeutically-active dose\] as a single agent or in combination with chemotherapy) and, in a subsequent rituximab/chemotherapy combination regimen, have no response (do not obtain a PR or better) to treatment or progress after the last dose of rituximab in a given regimen, even if the subsequent regimen included less than 2 doses of rituximab. Participants could receive additional systemic treatment after the qualifying rituximab regimen.
• The participant has received treatment with at least 1, but no more than 3, previous chemotherapy regimens. A regimen is defined as a new treatment combination or agent. Retreatment with the identical regimen or agent does not count as a new regimen; however, change from cyclophosphamide, vincristine, and prednisolone (CVP) to cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is counted as a new regimen. Rituximab, radioimmunotherapy, or other biologic treatments not combined with chemotherapy are not counted as a regimen.
• The participant has a bidimensionally measurable disease with at least 1 lesion measuring 2.0 centimeters (cm) or more in a single dimension. Participants who have previous involved-field irradiation can be included, provided the irradiated area is not the only source of measurable disease.
• The participant has a World Health Organization (WHO) performance status of 0, 1, or 2.
• The participant has absolute neutrophil count (ANC) 1000 cells/mm\^3 or more and platelet count 85000 cells/mm\^3 or more.
• The participant has a creatinine clearance of more than 30 mL/min as determined by the Cockcroft-Gault calculation.
• The participant has adequate hepatic function (no more than 2.5 times the upper limit of normal (ULN) for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and no more than 1.5 times the upper limit of the normal range (ULN) for total bilirubin). Participants with nonclinically significant elevations of bilirubin due to Gilbert's disease are eligible.
• The participant has had a bone marrow biopsy within 6 weeks before the 1st dose of bendamustine.
• Women of childbearing potential (not surgically sterile or 1 year postmenopausal) must use a medically accepted method of contraception and must agree to continue use of this method starting 2 weeks before the start of study drug treatment, during study drug treatment, and for 3 months after the end of study drug treatment. Acceptable methods of contraception include abstinence, barrier method with spermicide, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
• Women of childbearing potential must have a negative serum or urine pregnancy test.
• Men not surgically sterile or who are capable of producing offspring must practice abstinence or use a barrier method of birth control, and must agree to continue use of this method starting 2 weeks before the start of study drug treatment, during study drug treatment, and for 3 months after the end of study drug treatment.

You may not qualify if:

• The participant has received previous radiotherapy, radioimmunotherapy, chemotherapy, or immunotherapy within 4 weeks before day 1 of cycle 1 or has failed to recover (to Common Terminology Criteria for Adverse Events \[CTCAE\] toxicity grade 1 or 2) from clinically significant nonhematologic adverse events due to any agents administered previously.
• The participant has received treatment with an investigational agent within 4 weeks of day 1 of cycle 1.
• The participant has a history of previous high-dose chemotherapy with allogeneic stem cell support (history of autologous stem cell support is permissible).
• The participant is receiving or has received treatment with therapeutic doses of systemic steroids within 4 weeks of day 1 of cycle 1. (Low doses of chronic steroids \[prednisone or equivalent\] up to 20 mg/day for non-neoplastic disorders or for indications other than lymphoma or lymphoma-related complications are permitted.)
• The participant has transformed disease.
• The participant has any history of central nervous system (CNS) or leptomeningeal lymphoma.
• The participant has, or has had within the past 5 years, an active malignancy other than the target cancer. The exceptions are prostate cancer (Gleason grade \<6 with prostate specific antigen \[PSA\] levels within the normal range), in situ cervical or breast carcinoma, and nonmelanoma skin cancer that have received definitive treatment.
• The participant is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study immediately.)
• The participant has a serious infection, medical condition, or psychiatric condition that, in the opinion of the investigator, might interfere with the achievement of the study objectives.
• The participant is known to be positive for human immunodeficiency virus (HIV), have active hepatitis B, or active hepatitis C (anti-hepatitis C virus \[HCV\] positive). Hepatitis B surface antigen must be tested. The determination of active disease is left up to the Investigator.
• The participant has a known hypersensitivity to mannitol.
• The participant has used bendamustine previously.

Sponsors & Collaborators

• Teva Branded Pharmaceutical Products R&D, Inc.: lead

Study Sites (27)

Teva Investigational Site 001

Beijing, 100021, China

Location

Teva Investigational Site 026

Beijing, 100029, China

Location

Teva Investigational Site 022

Beijing, 100044, China

Location

Teva Investigational Site 004

Beijing, 100071, China

Location

Teva Investigational Site 003

Beijing, 100142, China

Location

Teva Investigational Site 002

Beijing, 100191, China

Location

Teva Investigational Site 023

Beijing, 100600, China

Location

Teva Investigational Site 016

Beijing, 100730, China

Location

Teva Investigational Site 021

Beijing, 110108, China

Location

Teva Investigational Site 015

Changchun, 130000, China

Location

Teva Investigational Site 010

Chengdu, 610041, China

Location

Teva Investigational Site 008

Guangzhou, 510000, China

Location

Teva Investigational Site 007

Guangzhou, 510060, China

Location

Teva Investigational Site 011

Hangzhou, 310003, China

Location

Teva Investigational Site 019

Harbin, 150081, China

Location

Teva Investigational Site 025

Hefei, 230022, China

Location

Teva Investigational Site 024

Lanzhou, 620102, China

Location

Teva Investigational Site 012

Nanjing, 210000, China

Location

Teva Investigational Site 013

Nanjing, 210029, China

Location

Teva Investigational Site 006

Shanghai, 200032, China

Location

Teva Investigational Site 005

Shanghai, 200035, China

Location

Teva Investigational Site 009

Shenyang, 110001, China

Location

Teva Investigational Site 027

Shenyang, 110042, China

Location

Teva Investigational Site 020

Suzhou, 215000, China

Location

Teva Investigational Site 014

Tianjin, 300041, China

Location

Teva Investigational Site 018

Xi'an, 710032, China

Location

Teva Investigational Site 017

Zhengzhou, 450000, China

Location

Related Publications (1)

• Shi YK, Hong XN, Yang JL, Xu W, Huang HQ, Xiao XB, Zhu J, Zhou DB, Han XH, Wu JQ, Zhang MZ, Jin J, Ke XY, Li W, Wu DP, Yang SM, Du X, Jia YQ, Liu AC, Liu DH, Shen ZX, Zhang LS, James L, Hellriegel E. Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study. Chin Med J (Engl). 2021 May 6;134(11):1299-1309. doi: 10.1097/CM9.0000000000001463.

  PMID: 33967195 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Teva Branded Pharmaceutical Products R&D, Inc.

USMedInfo@tevapharm.com

1-888-483-8279

Study Officials

• Teva Medical Expert, MD

  Teva Branded Pharmaceutical Products R&D, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2012
• First Posted: May 11, 2012
• Study Start: August 6, 2012
• Primary Completion: June 18, 2015
• Study Completion: April 24, 2017
• Last Updated: May 26, 2023
• Results First Posted: May 26, 2023

Record last verified: 2023-05

Locations

CN (27)