Bendamustine in the Treatment of Chinese Patients With Indolent Non-Hodgkin Lymphoma Refractory to Rituximab Treatment

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Teva Pharmaceutical Industries
Sponsor:
Information provided by (Responsible Party):
Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier:
NCT01596621
First received: May 2, 2012
Last updated: September 30, 2014
Last verified: September 2014
  Purpose

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 patients with indolent non-Hodgkin lymphoma (NHL) that has progressed after rituximab or a rituximab-containing therapy.


Condition Intervention Phase
Non-Hodgkin Lymphoma
Drug: Bendamustine hydrochloride
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Teva Pharmaceutical Industries:

Primary Outcome Measures:
  • Overall response rate (ORR) [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
    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) for patients who achieved a best response of PR or better [ Time Frame: up to 2.5 Years ] [ Designated as safety issue: No ]
    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 for all patients [ Time Frame: up to 2.5 Years ] [ Designated as safety issue: No ]
    Progression free survival (PFS) is defined as the time from the date of the 1st administration of bendamustine to the 1st documentation of disease progression/relapse, new anticancer therapy, or death (regardless of cause), whichever occurred first for all patients.

  • Pharmacokinetic Parameters [ Time Frame: Prior to the start of infusion on Day 1 for up to 24 hours during Cycle 1 ] [ Designated as safety issue: No ]

    Blood samples will be collected from a subset of 15 patients during Cycle 1 at a minimum of 3 study centers to evaluate the following:

    • maximum observed plasma drug concentration (Cmax)
    • time to maximum observed drug concentration (tmax) by inspection
    • area under the plasma drug concentration by time curve from time 0 to the time of the last measurable drug concentration (AUC0-t)
    • AUC from time zero to infinity (AUC0-∞)
    • percentage extrapolation
    • apparent plasma terminal elimination rate constant (λz) and associated half-life (t½)

  • Safety Parameters [ Time Frame: From signing of the informed consent form through 30 days after the last administration ] [ Designated as safety issue: Yes ]

    Safety will be assessed by the following:

    • occurrence of adverse events throughout the study
    • clinical laboratory (serum chemistry and hematology) test results
    • vital signs (blood pressure, pulse, and body temperature) measurements
    • World Health Organization (WHO) performance status
    • electrocardiogram (ECG) findings
    • concomitant medication usage
    • the need for hematologic supportive care


Estimated Enrollment: 100
Study Start Date: July 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine hydrochloride
This is a single-arm study, in which all subjects enrolled are administered the study drug.
Drug: Bendamustine hydrochloride
Bendamustine will be supplied in 20-mL, amber, single-use vials containing 100 mg of bendamustine hydrochloride as a white to off-white lyophilized powder. The drug will be labeled as study drug with the study number and batch number. Patients will be administered bendamustine hydrochloride 120mg/m^2 as a 60-minute infusion, and not more than 120 minutes, on days 1 and 2 of each 21-day treatment cycle for 6 planned cycles or up to 8 total cycles. Dose reductions or modifications may be made as appropriate. Day 1 only of the 21-day cycle may be ±1 day. Day 2 dosing should begin 24 ±4 hours after the start of the day 1 dose.
Other Name: Treanda®

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 patients 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. Patients are expected to participate in this study for approximately 2.5 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients are included in the study if all of the following criteria are met:

  1. The patient has documented relapse from indolent B-cell NHL. Patients with the following subtypes of indolent NHL are eligible for this study:

    • small lymphocytic lymphoma (peripheral B cell count <5000 cells/mm3)
    • lymphoplasmacytic lymphoma
    • splenic marginal zone B-cell lymphoma (±villous lymphocytes)
    • extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type
    • nodal marginal zone lymphoma (±monocytoid B-cells)
    • follicle center lymphoma
    • follicular (grade 1, 2, or 3a) lymphoma
  2. The patient has disease documented to have progressed despite rituximab treatment. The patient's disease is considered to be rituximab refractory if any of the following criteria are met at any time during the patient's treatment history (progression must be documented by computed tomography [CT] scan or magnetic resonance imaging [MRI] or biopsy) or if a patient 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)]:

    • rituximab-only regimen: Patients who receive a full course of single-agent rituximab (at least 2 doses of 375 mg/m2 [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: Patients who have a history of a full course of rituximab (at least 2 doses of 375 mg/m2 [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: Patients who receive a full course of rituximab (at least 2 doses of 375 mg/m2 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: Patients who have a history of a full course of rituximab treatment (at least 2 doses of 375 mg/m2 [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. Patients could receive additional systemic treatment after the qualifying rituximab regimen.
  3. The patient 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.
  4. The patient has a bidimensionally measurable disease with at least 1 lesion measuring 2.0 cm or more in a single dimension. Patients who have previous involved-field irradiation can be included, provided the irradiated area is not the only source of measurable disease.
  5. The patient is at least 18 years old at the time of informed consent.
  6. The patient has a WHO performance status of 0, 1, or 2.
  7. The patient has absolute neutrophil count (ANC) 1000 cells/mm3 or more and platelet count 85000 cells/mm3 or more.
  8. The patient has a creatinine clearance of more than 30 mL/min as determined by the Cockcroft-Gault calculation.
  9. The patient has adequate hepatic function (no more than 2.5 times the 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). Patients with nonclinically significant elevations of bilirubin due to Gilbert's disease are eligible.
  10. The patient has had a bone marrow biopsy within 6 weeks before the 1st dose of bendamustine.
  11. 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.
  12. Women of childbearing potential must have a negative serum or urine pregnancy test.
  13. 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.
  14. The patient has an estimated life expectancy of at least 3 months.
  15. The patient (or patient's legal representative) provides written informed consent.

Exclusion Criteria:

Patients are excluded from participating in this study if 1 or more of the following criteria are met:

  1. The patient 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.
  2. The patient has received treatment with an investigational agent within 4 weeks of day 1 of cycle 1.
  3. The patient has received hematopoietic growth factors within 4 weeks of day 1 of cycle 1. However, patients receiving chronic erythropoietin treatment are eligible for inclusion in this study.
  4. The patient has a history of previous high-dose chemotherapy with allogeneic stem cell support (history of autologous stem cell support is permissible).
  5. The patient 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.)
  6. The patient has transformed disease.
  7. The patient has any history of central nervous system (CNS) or leptomeningeal lymphoma.
  8. The patient 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.
  9. The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study immediately.)
  10. The patient 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.
  11. The patient 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.
  12. The patient has a known hypersensitivity to mannitol.
  13. The patient has used bendamustine previously.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01596621

Contacts
Contact: US Teva Medical Information 800-896-5855

Locations
China
Teva Investigational Site 001 Recruiting
Beijing, China
Teva Investigational Site 004 Recruiting
Beijing, China
Teva Investigational Site 002 Recruiting
Beijing, China
Teva Investigational Site 021 Not yet recruiting
Beijing, China
Teva Investigational Site 022 Not yet recruiting
Beijing, China
Teva Investigational Site 016 Recruiting
Beijing, China
Teva Investigational Site 026 Recruiting
Beijing, China
Teva Investigational Site 003 Recruiting
Beijing, China
Teva Investigational Site 023 Not yet recruiting
Beijing City, China
Teva Investigational Site 015 Recruiting
Changchun, China
Teva Investigational Site 010 Recruiting
Chengdu, China
Teva Investigational Site 007 Recruiting
Guangzhou, China
Teva Investigational Site 008 Recruiting
Guangzhou, Guangdong Province, China
Teva Investigational Site 011 Recruiting
Hangzhou, , Zhejiang, China
Teva Investigational Site 019 Recruiting
Harbin, China
Teva Investigational Site 025 Not yet recruiting
Hefei, China
Teva Investigational Site 024 Recruiting
Lanzhou, China
Teva Investigational Site 013 Recruiting
Nanjing, Jiangsu Province, China
Teva Investigational Site 012 Recruiting
Nanjing,Jiangsu Province, China
Teva Investigational Site 006 Recruiting
Shanghai, China
Teva Investigational Site 005 Recruiting
Shanghai, China
Teva Investigational Site 027 Recruiting
Shenyang, China
Teva Investigational Site 009 Recruiting
Shenyang City, Liaoning Province, China
Teva Investigational Site 020 Recruiting
Sushow, China
Teva Investigational Site 018 Recruiting
Xi'an, China
Teva Investigational Site 017 Recruiting
Zhengzhou, China
Sponsors and Collaborators
Teva Branded Pharmaceutical Products, R&D Inc.
  More Information

No publications provided

Responsible Party: Teva Pharmaceutical Industries ( Teva Branded Pharmaceutical Products, R&D Inc. )
ClinicalTrials.gov Identifier: NCT01596621     History of Changes
Other Study ID Numbers: C18083/3076
Study First Received: May 2, 2012
Last Updated: September 30, 2014
Health Authority: China: Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by Teva Pharmaceutical Industries:
Bendamustine hydrochloride
CEP-18083
Treanda®
Non-Hodgkin Lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bendamustine
Nitrogen Mustard Compounds
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 19, 2014