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
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 . 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.
|Condition or disease||Intervention/treatment||Phase|
|T-cell Lymphoma||Drug: BCD chemotherapy (Bendamustine, Carboplatin, Dexamethasone)||Phase 2|
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) . 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 . 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 . 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 . 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 . 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 :||Interventional (Clinical Trial)|
|Actual Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma: BENCART Trial|
|Actual Study Start Date :||May 2015|
|Actual Primary Completion Date :||September 2017|
|Actual Study Completion Date :||September 2017|
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 Name: BCD chemotherapy
- 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
- 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 ]