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Non-Hodgkin LymphomaPhase 3NCT01596621

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

A Phase 3 study testing Bendamustine hydrochloride in people with Non-Hodgkin Lymphoma, run by Teva Branded Pharmaceutical Products R&D, Inc. at 27 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-Hodgkin Lymphoma
What is being tested?
Bendamustine hydrochloride
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
102 participants
Where
27 sitesChina
Study dates
6 Aug 2012to 24 Apr 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
  • 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.
  • 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.
  • 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.
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  • 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.
  • The participant has an estimated life expectancy of at least 3 months.
  • The participant (or participant's legal representative) provides written informed consent.

Who cannot join

  • 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 received hematopoietic growth factors within 4 weeks of day 1 of cycle 1. However, participants receiving chronic erythropoietin treatment are eligible for inclusion in this study.
  • 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.
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  • 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.

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

China27 sites

  • Teva Investigational Site 001

    Beijing, 100021

  • Teva Investigational Site 026

    Beijing, 100029

  • Teva Investigational Site 022

    Beijing, 100044

  • Teva Investigational Site 004

    Beijing, 100071

  • Teva Investigational Site 003

    Beijing, 100142

  • Teva Investigational Site 002

    Beijing, 100191

  • Teva Investigational Site 023

    Beijing, 100600

  • Teva Investigational Site 016

    Beijing, 100730

  • Teva Investigational Site 021

    Beijing, 110108

  • Teva Investigational Site 015

    Changchun, 130000

  • Teva Investigational Site 010

    Chengdu, 610041

  • Teva Investigational Site 008

    Guangzhou, 510000

  • Teva Investigational Site 007

    Guangzhou, 510060

  • Teva Investigational Site 011

    Hangzhou, 310003

  • Teva Investigational Site 019

    Harbin, 150081

  • Teva Investigational Site 025

    Hefei, 230022

  • Teva Investigational Site 024

    Lanzhou, 620102

  • Teva Investigational Site 012

    Nanjing, 210000

  • Teva Investigational Site 013

    Nanjing, 210029

  • Teva Investigational Site 006

    Shanghai, 200032

  • Teva Investigational Site 005

    Shanghai, 200035

  • Teva Investigational Site 009

    Shenyang, 110001

  • Teva Investigational Site 027

    Shenyang, 110042

  • Teva Investigational Site 020

    Suzhou, 215000

  • Teva Investigational Site 014

    Tianjin, 300041

  • Teva Investigational Site 018

    Xi'an, 710032

  • Teva Investigational Site 017

    Zhengzhou, 450000

Other trials in China

About this study

Official title: An Open-Label Study to Evaluate Bendamustine Hydrochloride in the Treatment of Chinese Patients With Indolent Non-Hodgkin Lymphoma (NHL) Refractory to Rituximab Treatment

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.

Read the detailed description

This is a multicenter, nonrandomized, open-label, single-agent clinical study conducted in China, and is designed to investigate the use of bendamustine in the treatment of Chinese participants with relapsed, rituximab-refractory indolent NHL. The study consists of a screening period of up to 4 weeks, a treatment period of approximately 24 weeks (up to eight 21-day cycles), and a long-term follow-up period for up to 2 years after the last dose of study drug. Participants are expected to participate in this study for approximately 2.5 years.

Being tested
Bendamustine hydrochloride
Keywords
Bendamustine hydrochloride, CEP-18083, Treanda®, Non-Hodgkin Lymphoma
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bendamustine hydrochlorideDrug

    Also called Treanda®

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

Study groups in NCT01596621
Study groupRoleWhat they receive
BendamustineExperimentalParticipants 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.
Receives: Drug: Bendamustine hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Duration of Response (DOR) (Assessed by IRC)

    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 masses ≥50% decrease in 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. Disease progression: any new lesion or increase by ≥50% of previously involved sites from nadir.

    Measured: 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)

  2. Progression-Free Survival (Assessed by IRC)

    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.

    Measured: 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)

  3. Maximum Observed Plasma Concentration (Cmax) of Bendamustine

    Measured: 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)

  4. Time to Reach Cmax (Tmax) of Bendamustine

    Measured: 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)

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

    Measured: 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)

  6. Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) of Bendamustine

    Measured: 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)

  7. Rate Constant for Elimination (λz) of Bendamustine

    Measured: 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)

  8. Percentage of the AUC0-∞ Based on Extrapolation (%AUCext)

    Measured: 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)

  9. Half-Life (t½) of Bendamustine

    Measured: 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)

  10. Number of Participants With Adverse Events (AEs)

    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'.

    Measured: From first administration of bendamustine through 30 days after the last administration (up to 2.5 Years)

  11. World Health Organization (WHO) Performance Status

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

    Measured: At the end of treatment (up to 2.5 years)

  12. Number of Participants Who Need At Least 1 Hematologic Supportive Care (Plasma, Blood Cells, or Cytokines)

    Measured: From first administration of bendamustine up to the end of treatment (up to 2.5 Years)

  13. Number of Participants With Concomitant Medication Usage

    Concomitant medications included all medications taken while the participant received study drug.

    Measured: From first administration of bendamustine up to the end of treatment (up to 2.5 Years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2012 (estimated)
  2. Study start6 Aug 2012
  3. Primary completion18 Jun 2015
  4. Study completion24 Apr 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
102 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01596621
Sponsor's protocol ID
C18083/3076
Status last verified
May 2023
First submitted
2 May 2012
Last updated
26 May 2023
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 33967195

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Bendamustine hydrochloride in people with Non-Hodgkin Lymphoma, run by Teva Branded Pharmaceutical Products R&D, Inc. at 27 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response Rate (ORR) (Assessed by Independent Review Committee [IRC]) (time frame: 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01596621, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2023.

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