Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma
Condition: T-cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): BCD chemotherapy (Bendamustine, Carboplatin, Dexamethasone)
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): BCD chemotherapy
Intervention MeSH terms: Dexamethasone; Carboplatin; Bendamustine Hydrochloride
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment