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

Sponsor

Teva Branded Pharmaceutical Products R&D, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01596621

Collaborator

(none)

102

Enrollment

Locations

Arm

56.6

Actual Duration (Months)

3.8

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma	Drug: Bendamustine hydrochloride	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

102 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 6, 2012

Actual Primary Completion Date :

Jun 18, 2015

Actual Study Completion Date :

Apr 24, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Bendamustine 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 Bendamustine will be be administered per dose and schedule specified in the arm description. Other Names: Treanda®

Arm

Intervention/Treatment

Experimental: Bendamustine

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

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

Other Names:

Treanda®

Outcome Measures

Primary Outcome Measures

Overall Response Rate (ORR) (Assessed by IRC) [Up to 2.5 Years]
The ORR is defined as the proportion of patients who achieve a best response of complete response (CR) or partial response (PR) during the study based on the modified International Workshop Response Criteria.

Secondary Outcome Measures

Duration of Response (DOR) (Assessed by IRC) [Up to 2.5 Years]
Duration of response (DOR) is defined as the time from the date of 1st documentation of response to the 1st documentation of disease progression, new anticancer therapy, or death (regardless of cause), whichever occurs first, for patients with a best response of CR or PR determined by the modified International Workshop Response Criteria.
Progression-Free Survival (Assessed by IRC) [Up to 2.5 Years]
Progression free survival (PFS) is 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 patients.
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]
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]
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]
Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC0-∞) of Bendamustine [Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1]
Rate Constant for Elimination (λz) of Bendamustine [Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1]
Percentage Extrapolation of Bendamustine [Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1]
Half-Life (t½) of Bendamustine [Prior to the start of infusion on Day 1 for up to 24 hours after the end of infusion during Cycle 1]
Number of Participants With Adverse Events (AEs) [From first administration of bendamustine up to 2.5 Years]
An AE is any untoward medical occurrence in a participant who receives study drug without regard to possibility of causal relationship. Serious adverse event (SAE) is 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 will include both SAEs and non-serious AEs.
World Health Organization (WHO) Performance Status [From first administration of bendamustine up to 30 days post last dose]
Number of participants with WHO performance status (improved, stayed the same, and deteriorated) at the end of treatment have been reported.
Number of Participants Who Need At Least 1 Hematologic Supportive Care (Plasma, Blood Cells, or Cytokines) [From first administration bendamustine through end of treatment (up to week 24)]
Number of Participants With Concomitant Medication Usage [From first administration bendamustine through end of treatment (up to week 24)]
Concomitant medications include all medications taken while the participant receives study drug.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.
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

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.

Exclusion Criteria:

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.
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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Teva Investigational Site 001	Beijing	China	100021
2	Teva Investigational Site 026	Beijing	China	100029
3	Teva Investigational Site 022	Beijing	China	100044
4	Teva Investigational Site 004	Beijing	China	100071
5	Teva Investigational Site 003	Beijing	China	100142
6	Teva Investigational Site 002	Beijing	China	100191
7	Teva Investigational Site 023	Beijing	China	100600
8	Teva Investigational Site 016	Beijing	China	100730
9	Teva Investigational Site 021	Beijing	China	110108
10	Teva Investigational Site 015	Changchun	China	130000
11	Teva Investigational Site 010	Chengdu	China	610041
12	Teva Investigational Site 008	Guangzhou	China	510000
13	Teva Investigational Site 007	Guangzhou	China	510060
14	Teva Investigational Site 011	Hangzhou	China	310003
15	Teva Investigational Site 019	Harbin	China	150081
16	Teva Investigational Site 025	Hefei	China	230022
17	Teva Investigational Site 024	Lanzhou	China	620102
18	Teva Investigational Site 012	Nanjing	China	210000
19	Teva Investigational Site 013	Nanjing	China	210029
20	Teva Investigational Site 006	Shanghai	China	200032
21	Teva Investigational Site 005	Shanghai	China	200035
22	Teva Investigational Site 009	Shenyang	China	110001
23	Teva Investigational Site 027	Shenyang	China	110042
24	Teva Investigational Site 020	Suzhou	China	215000
25	Teva Investigational Site 014	Tianjin	China	300041
26	Teva Investigational Site 018	Xi'an	China	710032
27	Teva Investigational Site 017	Zhengzhou	China	450000