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

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Brief Title

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

Official Title

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Overall response rate

Secondary Outcome

 Toxicity profiles (Adverse Events and Laboratory Results)

Condition

T-cell Lymphoma

Intervention

BCD chemotherapy (Bendamustine, Carboplatin, Dexamethasone)

Study Arms / Comparison Groups

 BCD chemotherapy
Description:  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

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

30

Start Date

May 2015

Completion Date

September 2017

Primary Completion Date

September 2017

Eligibility Criteria

        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.
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

, , 



Administrative Informations


NCT ID

NCT02424045

Organization ID

2014-12-012


Responsible Party

Principal Investigator

Study Sponsor

Samsung Medical Center


Study Sponsor

, , 


Verification Date

September 2018