Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma

September 4, 2018 updated by: Won Seog Kim, Samsung Medical Center

A Phase II Trial of Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma: BENCART Trial

BCD (Bendamustine, carboplatin and dexamethasone)chemotherapy regimen is proposed as the salvage treatment for relapsed or refractory PTCLs in this study protocol, which would be expected to show more promising clinical outcomes than that of bendamustine single therapy. Platinum combination with bendamustine is a theoretically ideal salvage regimen for the patients of PTCLs because these both agents are highly effective drugs in lymphoma treatment and have rare cross-resistance. Carboplatin was selected as a platinum agent for combination with bendamustine, which is a second generation platinum agent and has a less neurotoxicity than that of cisplatin, considering use for previously treated patients with vinc alkaloid agents.

In a prior phase I study of carboplatin in combination with bendamustine for previously untreated small cell lung cancer patients, the recommended dose for phase II studies was bendamustine 100 mg/m2 on day 1 and 2, carboplatin AUC 5 on day 1, respectively [16]. In consideration of previously treated subjects, however, the dose of bendamustine was decided on 80mg/m2 in this study protocol with concerning about the toxicities, especially to severe cytopenia.

Dexamethasone is one of the corticosteroids using a key drug for lymphoid malignancy and has a strong antiemetic effect. Therefore, dexamethasone could enhance the therapeutic efficacy and antiemetic effect, using with bendamustine and carboplatin.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Peripheral T-cell lymphoma (PTCL) represents a heterogeneous group of nodal and extranodal mature T-cell lymphomas, which constitute about 5 - 10% of all non-Hodgkin lymphomas (NHLs) in Western countries compared to 20 - 30% of all lymphomas in the East Asia. The most common histologies include PTCL, not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large cell lymphoma (ALCL) [3]. Most of these subtypes include a high percentage of patients with advanced disease stage, widespread dissemination and aggressive behavior. As a result, the prognosis of PTCL remains dismal, with the 5-year overall survival (OS) rate for many of these subtypes ranging between 25 and 45%, except for ALCL (ALK ), which demonstrates a better 5-year OS (70%) [4 - 6]. Thus, new therapeutic strategies are needed to improve the survival of patients with PTCL.

Current multiagent chemotherapeutic regimens for patients with PTCL are extrapolated mainly from therapeutic paradigms of B-cell lymphomas, with the cornerstone treatment being an anthracycline-containing regimen. Although some patients with PTCL can be cured with these approaches, relapsed and chemorefractory disease constitutes a significant clinical dilemma in the care of these patients [7]. At present, high dose chemotherapy with autologous stem cell support seems to offer potential curative treatment for those patients with relapsed PTCL who are responsive to salvage chemotherapy [8]. However, the majority of elderly patients with relapsed or refractory PTCL cannot benefit from high dose chemotherapy as a result of advanced age, significant comorbidities, poor functional status, toxicities from previous treatments and inherent chemoresistance [9]. Conventional salvage regimens have been mostly designed for younger or fitter populations, and can hardly be delivered to these elderly patients due to marked hematologic and non-hematologic toxicities, mainly involving renal and neurological functions [10]. Therefore, it is imperative that innovative salvage regimens based on drug combinations with increased efficacy and reduced toxicity be explored for the management of elderly patients with relapsed or refractory PTCLs.

BCD chemotherapy regimen is proposed as the salvage treatment for relapsed or refractory PTCLs in this study protocol, which would be expected to show more promising clinical outcomes than that of bendamustine single therapy. Platinum combination with bendamustine is a theoretically ideal salvage regimen for the patients of PTCLs because these both agents are highly effective drugs in lymphoma treatment and have rare cross-resistance. Carboplatin was selected as a platinum agent for combination with bendamustine, which is a second generation platinum agent and has a less neurotoxicity than that of cisplatin, considering use for previously treated patients with vinc alkaloid agents.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 71 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Histologically proven aggressive T-cell Non-Hodgkin's lymphoma (NHL)
  2. Age 18 -75 years
  3. Ann Arbor stage II, III and IV (Appendix A)
  4. Relapsed or refractory cases to previous treatments
  5. Performance status (ECOG) ≤ 2 (Appendix B)

  6. At least one or more bidimensionally measurable lesion(s)

    • ≥ 2 cm by conventional CT
    • ≥ 1 cm by spiral CT
    • skin lesion (photographs should be taken) ≥ 2 cm
    • measurable lesion by physical examination ≥ 2 cm
  7. Cardiac ejection fraction ≥ 50 % as measured by MUGA or 2DECHO without clinically significant abnormalities
  8. Adequate renal function: serum creatinine level < 2 mg/dL (177 μmol/L)
  9. Adequate liver functions: Transaminase (AST/ALT) < 3 X upper normal value (or < 5 x ULN in the presence of DLBCL involvement of the liver), Bilirubin < 2 X upper normal value (or < 5 x ULN in the presence of PTCL involvement of the liver)
  10. Adequate BM functions: hemoglobin ≥ 9 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL, unless abnormalities are due to bone marrow involvement by lymphoma
  11. A negative serum or urine pregnancy test prior to treatment must be available both for pre-menopausal women and for women who are < 1years after the onset of menopause.
  12. Informed consent

Exclusion Criteria:

  1. ALK-positive anaplastic large cell lymphoma and Sezary syndrome.
  2. CNS or testis involvement.
  3. Previously treated with the regimen containing bendamustine or platinum agents.
  4. Any other malignancies within the past 5 years except curatively treated non-melanoma skin cancer or in situ carcinoma of cervix uteri
  5. Pregnant or lactating women, women of childbearing potential not employing adequate contraception
  6. Other serious illness or medical conditions
  7. Unstable cardiac disease despite treatment, myocardial infarction within 6 months prior to study entry
  8. History of significant neurologic or psychiatric disorders including dementia or seizures
  9. Active uncontrolled infection (viral, bacterial or fungal infection)
  10. Other serious medical illnesses
  11. Known hypersensitivity to any of the study drugs or its ingredients
  12. Concomitant administration of any other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: BCD chemotherapy

All patients are scheduled to receive 2 cycles of three-weekly Bendamustine, carboplatin and dexamethasone combination chemotherapy(BCD Chemotherapy).

D1,D2 Bendamustine 80mg/m2 IV over 30-60min D1 Carboplatin AUC 5.0 IV D1-4 Dexamethasone 40mg #2 PO or IV
Drug: BCD chemotherapy (Bendamustine, Carboplatin, Dexamethasone)
All patients are scheduled to receive 2 cycles of three-weekly BCD. After 2 cycles of BCD, if the patients with complete remission (CR) or partial remission (PR) would be eligible for autologous stem cell transplantation (ASCT), stem cell collection after 3rd cycle of BCD and high dose chemotherapy and ASCT will be conducted. While ineligible patients to ASCT with non-progressive disease after 2 cycles of BCD, will be given 4 additional courses of the BCD regimen.
Other Names:
  • BCD chemotherapy

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Overall response rate
Time Frame: 3 years
They should be classified as complete remission (CR), partial remission (PR), stable disease (SD), or progressive disease (PD) according to the Revised Response Criteria for Malignant Lymphoma
3 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Toxicity profiles (Adverse Events and Laboratory Results)
Time Frame: 3 years
Toxicity profiles as measured by Adverse Events and Laboratory Results.The intensity of clinical adverse events will be graded according to the NCI CTCAE version 4.0.
3 years
Progression free survival
Time Frame: 3 years
Time to disease progression is defined as the time from treatment start to the first recording of relapse or disease progression or death of any cause.
3 years
Overall survival
Time Frame: 3 years
Duration of survival is defined as the time from treatment start to death of any cause or the date of last follow-up. Patients who are alive will be censored using the date at which they are last known to be alive.
3 years
Incidence of febrile neutropenia
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Samsung Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2017

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 15, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 22, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 6, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 4, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2014-12-012

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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