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A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial.

ABSTRACT: Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting. This phase 2 study evaluated a novel front-line combination whereby cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternated with pralatrexate (CEOP-P) in PTCL. Patients achieving a complete or partial remission (CR/PR) were eligible for consolidative stem cell transplantation (SCT) after 4 cycles. Thirty-three stage II-IV PTCL patients were treated: 21 PTCL-not otherwise specified (64%), 8 angioimmunoblastic T cell lymphoma (24%) and 4 anaplastic large cell lymphoma (12%). The majority (61%) had stage IV disease and 46% were International Prognostic Index high/intermediate or high risk. Grade 3-4 toxicities included anaemia (27%), thrombocytopenia (12%), febrile neutropenia (18%), mucositis (18%), sepsis (15%), increased creatinine (12%) and liver transaminases (12%). Seventeen patients (52%) achieved a CR. The 2-year progression-free survival and overall survival, were 39% (95% confidence interval 21-57) and 60% (95% confidence interval 39-76), respectively. Fifteen patients (45%) (12 CR) received SCT and all remained in CR at a median follow-up of 21·5 months. CEOP-P did not improve outcomes compared to historical data using CHOP. Defining optimal front line therapy in PTCL continues to be a challenge and an unmet need.

SUBMITTER: Advani RH

PROVIDER: S-EPMC5642048 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial.

Advani Ranjana H RH Ansell Stephen M SM Lechowicz Mary J MJ Beaven Anne W AW Loberiza Fausto F Carson Kenneth R KR Evens Andrew M AM Foss Francine F Horwitz Steven S Pro Barbara B Pinter-Brown Lauren C LC Smith Sonali M SM Shustov Andrei R AR Savage Kerry J KJ Vose Julie M JM

British journal of haematology 20151202 4

Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes using conventional CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy. The anti-folate pralatrexate, the first drug approved for patients with relapsed/refractory PTCL, provided a rationale to incorporate it into the front-line setting. This phase 2 study evaluated a novel front-line combination whereby cyclophosphamide, etoposide, vincristine and prednisone (CEOP) alternated with pralatrexate (CEOP-P) in PTCL. P ...[more]

PMID: 26627450

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Project description:BackgroundData suggests that males experience less toxicity and poorer survival than females treated for Ewing's sarcoma. We instituted an intra-patient dose escalation (DE) policy with Vincristine/Doxorubicin/Cyclophosphamide (VDC) alternating with Ifosfamide/Etoposide (IE) based on hematological nadirs and report its feasibility and safety.MethodsA retrospective review of adherence to DE guidelines and toxicities was conducted for patients who received DE with VDC/IE over 3 years at a single cancer center. Absolute neutrophil counts (ANC) was collected on days 8, 12 and 15 for cycles 1-6. DE of 10%/cycle was applied if ANC?>?1.5×109/L and platelet?>?100×109/L on all blood results. The primary endpoint was the proportion of patients who received appropriate DE. The secondary endpoint was to assess morbidity, changes in hematologic nadirs between gender and age and a comparison with a prior cohort of ESFT patients who did not receive DE. Gender comparisons were assessed via independent 2-sample t-tests assuming unequal variances. Within cycle changes in hematologic nadirs were assessed using repeated measures ANOVA. Relapse free survival and overall survival (OS) curves were estimated using the Kaplan-Meier method.Results23 patients were identified (mean age: 27; range 17-54). 91 decisions for DE were made (1 decision excluded because of progressive disease) with 90% concordance with guidelines. No adverse outcomes occurred as a result of the inappropriate escalation. Grade 3/4 febrile neutropenia (FN) during VDC and IE was 26.1% (6/23 patients) and 17.4% respectively with no difference for those who were DE. Males were less neutropenic after C1 and C3 of VDC compared to females (P-value C1?=?0.003; C3?=?0.005). VDC was associated with greater neutropenia on day 8 whereas IE had greater neutropenia on day 12 (P-value <0.001). During VDC, a non statistical difference in neutropenia was seen for individuals aged 15-25 (n?=?13) compared with older individuals (P-value?=?0.09). OS comparison for those with localized disease with a prior cohort who were not DE showed similar outcomes (P-value?=?0.37).ConclusionsDE is deliverable without increased adverse outcomes. Males have less myelosuppression during VDC, and should be especially considered for DE.

Project description:BackgroundMYC gene rearrangement is present in approximately 10% of aggressive B-cell lymphomas, with half also harbouring a BCL2 gene rearrangement. Multiple retrospective studies of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone) have shown a worse outcome in patients with MYC rearrangement (alone or with rearrangement of BCL2 or BCL6, or both) than in patients without MYC rearrangement, and suggest improved outcomes after more intensive treatment. We aimed to determine the outcome of dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; DA-EPOCH-R), an intensive infusional treatment regimen, in untreated aggressive B-cell lymphoma with MYC rearrangement.MethodsWe present the final analysis of a prospective, multicentre, single-arm, phase 2 study of DA-EPOCH-R in patients with untreated aggressive B-cell lymphoma with MYC rearrangement. DA-EPOCH-R was scheduled to be administered with CNS prophylaxis for six cycles. Primary endpoints included event-free and overall survival. This study is registered with ClinicalTrials.gov (NCT01092182).Findings53 patients were enrolled, with median age of 61 years (range 29-80; IQR 50-70); 43 (81%) patients had stage III-IV disease and 26 (49%) had high-intermediate or high international prognostic index (IPI) scores. 19 patients had confirmed MYC rearrangement alone (single-hit) and 24 also had rearrangement of BCL2, BCL6, or both (double-hit), with similar characteristics between these two groups. After a median follow-up of 55·6 months (IQR 50·5-61·1), 48-month event-free survival was 71·0% (95% CI 56·5-81·4) and 48-month overall survival was 76·7% (95% CI 62·6-86·1) for all patients. Toxicity included grade 4 neutropenia in 160 (53%) of 301 cycles, grade 4 thrombocytopenia in 40 (13%) cycles, and any grade of fever with neutropenia in 56 (19%) cycles. There were three treatment-related deaths (all infections).InterpretationIn this study, DA-EPOCH-R produced durable remission in patients with MYC-rearranged aggressive B-cell lymphomas and should be considered for the treatment of these diseases.FundingCancer Trials Support Unit and Center for Cancer Research of the National Cancer Institute and Genentech.

Project description:ObjectiveChidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma (PTCL). This phase 1b study evaluated the safety, pharmacokinetics, and preliminary efficacy of chidamide in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) for treatment-naïve PTCL patients.MethodsThis study was an open-label, multicenter trial composed of dose escalation and dose expansion. Patients received CHOP for six 21-d cycles and chidamide on d 1, 4, 8 and 11 in each cycle. Four dose levels of chidamide (20, 25, 30 and 35 mg) were evaluated. The primary objective was to evaluate the safety and tolerability of the combination regimen.ResultsA total of 30 patients were evaluated in this study: 15 in the dose-escalation part and 15 in the dose-expansion part. In the dose-escalation study, three patients were enrolled in the 35 mg chidamide cohort. One had dose-limiting toxicity with grade 3 vascular access complications, and one had grade 2 neutropenia with a sustained temperature >38 °C. Dose escalation was stopped at this chidamide dose level. The most common (≥10%) grade 3 or 4 adverse events (AEs) were leukopenia (90.0%), neutropenia (83.3%), vomiting (13.3%), thrombocytopenia (10.0%) and febrile neutropenia (10.0%). No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment. The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3% (25/28), with 16 (57.1%) achieving complete response or unconfirmed complete response. The estimated median progression-free survival was 14.0 months. In summary, we chose chidamide 30 mg as the recommended dose for phase 2.ConclusionsThe addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients, which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.

Project description:IntroductionBrentuximab vedotin (BV) showed high overall remission rates in refractory/relapsed classical Hodgkin's lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). Although the efficacy of BV has been reported in clinical trials, its efficacy as a frontline therapy in real world for patients with CD30 positive subtypes of non-Hodgkin's lymphoma (NHL) such as peripheral T-cell lymphoma with T-follicular helper cell (TFH) phenotype (PTCL, TFH), anaplastic large-cell lymphoma (ALCL) and angioimmunoblastic T-cell lymphoma (AITL) in China has not been well documented.MethodsAnalysis of a real-world, observational, retrospective case series in patients suffering from AITL, sALCL and peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) and other types of PTCL treated with BV in frontline treatment was conducted. The patients were given treatment from May 2020 till June 28, 2021. All patients were pathologically diagnosed to have PTCL before treatment and expressed CD30. Patients received BV (1.8 mg/kg) combined with CEP (cyclophosphamide, epirubicin, prednisone acetate every 3 weeks). The primary endpoint was objective response rates (ORR), and secondary endpoints were duration of response and incidence of adverse events (AEs). Exploratory endpoints such as progression-free survival (PFS) are discussed even though after such a short period.ResultsNineteen patients completed ≥ 1 cycles of BV-CEP treatment (16 cases completed ≥ 4 cycles, 3 cases only completed 1 cycle). Among them, the ORR reached 89.5% [CR 52.7%; partial response (PR) 36.8%]. In the ALCL group, CR reached 100% with the median duration of response of up to 8 months, while in the AITL group, the ORR was 75% and 2 patients had disease progression after treatment with BV + CEP. We also observed that BV-CEP may extend the PFS compared to traditional chemotherapy such as the CHOEP regimen (BV-CEP: not evaluable, CHOEP: 6.5 months), although the median follow-up was only 6.7 months. Adverse events (AEs), including incidence and severity of febrile neutropenia (26% patients in the BV-CEP group and 30% in the CHOEP group), were similar between groups. There was no incidence of AEs leading to treatment withdrawal or death under BV-CEP treatment.ConclusionBV is a promising treatment in patients with ALCL, AITL and PTCL-TFH in frontline treatment settings.

Dataset Information

A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial.

Publications

A phase II study of cyclophosphamide, etoposide, vincristine and prednisone (CEOP) Alternating with Pralatrexate (P) as front line therapy for patients with peripheral T-cell lymphoma (PTCL): final results from the T- cell consortium trial.

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