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

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ClinicalTrials.gov Identifier: NCT02424045
Recruitment Status : Completed
First Posted : April 22, 2015
Last Update Posted : September 6, 2018
Sponsor:
Information provided by (Responsible Party):
Won Seog Kim, Samsung Medical Center

Tracking Information
First Submitted Date  ICMJE April 15, 2015
First Posted Date  ICMJE April 22, 2015
Last Update Posted Date September 6, 2018
Actual Study Start Date  ICMJE May 2015
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02424045 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 21, 2015)
  • 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.
  • 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.
  • 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.
  • Incidence of febrile neutropenia [ Time Frame: 3 years ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma
Official Title  ICMJE A Phase II Trial of Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma: BENCART Trial
Brief Summary

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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE T-cell Lymphoma
Intervention  ICMJE 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 Name: BCD chemotherapy
Study Arms  ICMJE 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

Intervention: Drug: BCD chemotherapy (Bendamustine, Carboplatin, Dexamethasone)
Publications * Park BB, Kim WS, Suh C, Hong JY, Yang DH, Lee WS, Do YR, Koh YI, Won JH, Kim MK, Jo JC, Hyun SY, Kim JA, Oh YH, Lee SS. A phase II trial of bendamustine, carboplatin, and dexamethasone for refractory or relapsed peripheral T-cell lymphoma (BENCART trial). Leuk Lymphoma. 2019 Jun 6:1-7. doi: 10.1080/10428194.2019.1622100. [Epub ahead of print]

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 21, 2015)
30
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2017
Actual Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02424045
Other Study ID Numbers  ICMJE 2014-12-012
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Won Seog Kim, Samsung Medical Center
Study Sponsor  ICMJE Samsung Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Samsung Medical Center
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP