Phase II Trial Of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) Chemotherapy For Patients With Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3037-3037 ◽  
Author(s):  
Seok Jin Kim ◽  
Dok Hyun Yoon ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background The treatment of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type has shifted to non-anthracycline-based intensive chemotherapy with radiotherapy since the poor response of ENKTL to anthracycline due to the expression of a multidrug-resistant (MDR) p-glycoprotein was proven. We previously proposed concurrent chemoradiotherapy (CCRT) followed by chemotherapy which is not affected by MDR and reported a significant improvement of outcomes of localized ENKTL. Based on our accumulated data, we designed a new treatment protocol. First, we added tri-weekly administration of L-asparaginase to reduce the probability of systemic progression during CCRT. Second, we designed MIDLE (methotrexate, ifosfamide, etoposide, dexamethasone, and L-asparaginase) according to previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 40 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly intravenous (IV) administration of 4,000 IU of Escherichia coli L-asparaginase was done. The chemotherapy, MIDLE (methotrexate 3g/m2 on day 1, etoposide 100mg/m2, Ifosfamide 1000mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days up to 2 cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30–77 years). 24 patients were male while only four patients were female. Twenty-two patients were stage IE and six were IIE. All patients completed CCRT, which resulted in 92.9% of overall response rate including 20 complete responses and 6 partial responses. One patient showed stable disease after CCRT whereas the other patient progressed. No grade 3 or 4 hematologic toxicity was found during CCRT. However, grade 3 non-hematologic toxicities included bilirubin elevation (n = 4), mucositis (n = 1), and nausea/vomiting (n = 6). After the completion of CCRT, 23 patients entered the MIDLE chemotherapy as five patients including one disease progression and four cases of withdrawal could not receive MIDLE. All patients achieved complete response after they completed the planned two cycles of MIDLE chemotherapy whereas two patients dropped out after their first cycle due to non-hematologic toxicity. The final complete response rate of patients enrolled was 92.9% (26/28). The major toxicity of MIDLE was grade 3/4 leucopenia, and the non-hematologic toxicity included mucositis and nausea/vomiting. The hepatic toxicity-associated with L-asparaginase was frequent. However, the majority of the hepatic toxicities were grade 1 or 2. With the median potential follow-up of 25 months (95% confidence interval: 19 – 31 months), four patients relapsed. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures: Kwak: celgene: Research Funding.

scholarly journals Final Report on Phase II Trial of L-Asparaginase Plus Concurrent Chemoradiotherapy Followed By Midle (Methotrexate, Ifosfamide, Etoposide, Dexamethasone, and L-asparaginase) Chemotherapy for Patients with Newly Diagnosed Stage I/II Extranodal NK/T-Cell Lymphoma, Nasal Type

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3942-3942
Author(s):  
Dok Hyun Yoon ◽  
Seok Jin Kim ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Background We previously have shown that concurrent chemoradiotherapy (CCRT) followed by chemotherapy such as VIPD (etoposide, ifosfamide, cisplatin and dexamethasone) or VIDL (etoposide, ifosfamide, dexamethasone and L-asparaginase) is an effective treatment for the management of localized extranodal NK/T-cell lymphoma (ENKTL), nasal type. To further improve efficacy, we designed a new treatment protocol, MIDLE (methotrexate, ifosfamide, dexamethasone, L-asparaginase and etoposide), which incorporates tri-weekly administration of L-asparaginase during CCRT to reduce the probability of systemic progression and high dose methotrexate to intensify chemotherapy based on previous excellent outcomes of methotrexate-containing regimens such as SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) and MLD (methotrexate, L-asparaginase, dexamethasone). Methods The treatment scheme of CCRT consisted of radiation 36-45 Gy and weekly administration of cisplatin 30 mg/m2 (total: 4 doses). During the CCRT, tri-weekly 4,000 IU of Escherichia coli L-asparaginase was administered intravenously (IV). The chemotherapy, MIDLE (methotrexate 3 g/m2 on day 1, etoposide 100 mg/m2, Ifosfamide 1000 mg/m2 on day 2-3, dexamethasone 40mg on day 1-4, and L-asparaginase 6000 IU/m2 IV on day 4, 6, 8, 10) was repeated every 28 days for two cycles. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov(NCT01238159). Results Twenty-eight patients with stage IE/IIE ENKTL were enrolled, and the median age was 51 years (range, 30-77 years). Twenty four patients were male while only four patients were female. Twenty-two patients had stage IE and six IIE disease. Twenty four were classified as low risk group and the other four intermediate group according to PINK-E (Kim SJ et al., EHA 2015 S110). All but two patients completed CCRT, which resulted in 85.7% of overall response rate including 16 complete responses (57.1%) and 8 partial responses (28.6%). One showed stable disease (SD) and the other one showed progressive disease (PD) with development of new distant lymph node involvement after CCRT. Grade 3 or 4 hematologic toxicity was not common. Only two patients experienced G3 neutropenia during or after CCRT. However, grade 3 non-hematologic toxicities were noted including bilirubin elevation (n = 3), mucositis (n = 1), anorexia (n=5) and nausea/vomiting (n = 11) Two could not complete CCRT according to the protocol due to G3 allergic reaction to L-asparaginase (n=1) and prolonged G3 mucositis (n=1). After the completion of CCRT, 23 out of 28 patients entered the MIDLE chemotherapy as five patients including one disease progression and four withdrawal during (n=2) or after (n=2) CCRT due to toxicities. All those who completed the planned two cycles of MIDLE chemotherapy achieved complete response after chemotherapy including those with PR (n=6) and SD (n=1) after CCRT. Three patients dropped out during or after their first cycle of MIDLE due to non-hematologic toxicities (recurrent G3 bilirubinemia (n=1), G3 increased creatinine (n=1), G5 infection (n=1)). The final complete response rate was 82% (23/28). It was associated with a significant rate of grade 3/4 neutropenia (n=21) and febrile neutropenia (n=10). Two patients experienced acute kidney injury (AKI) during the first cycle of MIDLE and one of them died of pneumonia complicated by sepsis. With a median follow-up of 46 months (95% confidence interval: 39 - 47 months), four patients progressed and five patients died with the estimated 3-year progression-free survival rate of 74.1% and overall survival rate of 81.5%. PINK-E could successfully stratify both time-to-progression (p=003) and overall survival (p=0.006) in this study. Conclusion L-asparaginase plus concurrent chemoradiotherapy followed by MIDLE chemotherapy may be an effective treatment strategy for stage I/II extranodal NK/T-Cell lymphoma, nasal type. However, higher numbers of patients were withdrawn during or after CCRT due to toxicity or poor tolerance than previous study. MIDLE chemotherapy was associated with high rate of G3 or 4 hematologic toxicities. Thus, this approach should be reserved for selected patients such as young fit but high risk of relapse. PINK-E can be a useful prognostic index for stage I/II extranodal NK/T-Cell lymphoma, nasal type. Disclosures No relevant conflicts of interest to declare.

Concurrent Chemo-Radiotherapy Followed by VIDL (Etoposide, Ifosfamide, Dexamethasone, L-asparaginase) Chemotherapy In Stage I/II Extranodal NK/T-Cell Lymphoma of Nasal Cavity/Nasopharynx

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1765-1765
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Jae-Yong Kwak ◽  
Deok-Hwan Yang ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Prognostic Index ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Major Toxicity ◽  
Nk T Cell ◽  
Grade 3

Abstract Abstract 1765 Background Localized extranodal NK/T-cell lymphoma (ENKTL) mainly occurs in nasal and/or nasopharynx. Thus, ENKTL shows a poor response to anthracycline-based chemotherapy because of the frequent expression of a multidrug-resistant p-glycoprotein, radiotherapy for localized disease produces a higher complete response rate than chemotherapy. However, when ENKTL is treated with radiation alone, local and systemic failures are frequently observed. Therefore, our group previously reported the improved outcome of concurrent chemo-radiotherapy (CCRT) with weekly administration of cisplatin followed by systemic chemotherapy VIPD (etoposide, ifosfamide, cisplatin and dexamethasone). However, the grade 3/4 hematologic toxicity was the major toxicity of VIPD. Thus, in consideration of the risk of toxicity of VIPD, we designed VIDL (etoposide, ifosfamide, dexamethasone, and L-asparaginase) as adjuvant to CCRT. Because etoposide and ifosfamide are less affected by p-glycoprotein, and NK lymphoma cells are known as being sensitive to L-asparaginase, we expected VIDL regimen could be more effective and less toxic than VIPD. Methods Thirty-one newly diagnosed stage IE/IIE nasal/nasopharynx ENKTL patients received CCRT (radiation 40–50.4 Gy and cisplatin 30 mg/m2 weekly). Two cycles of VIDL (etoposide 100 mg/m2 D1–D3, ifosfamide 1200 mg/m2 D1–D3, dexamethasone 40 mg D1–D3, and L-asparaginase 4000IU/m2) were scheduled after CCRT. All patients provided informed written consents and this trial was registered at www.ClinicalTrials.gov (NCT01007526). Results The median age was 46.5 years (range, 22–71 years); 78.1% of all patients were younger than 60 years of age, and male (n = 21) to female (n = 11) was 2:1. Twenty-two patients were stage IE and nine were IIE. The majority of patients were in the low (n = 24) or low–intermediate (n = 6) risk categories of the International Prognostic Index. However, when we grouped patients based on the NK/T cell lymphoma prognostic index (NKPI) proposed previously for ENKTL, which includes the presence of B cell symptoms, lesions at stage III or IV, elevated serum LDH concentration, and lymph node involvement, 25 patients belonged to group I or II and 7 patients were group III or IV (those with more than two risk factors). All patients completed CCRT, which resulted in 90.3% overall response rate including 22 complete response (CR) and 6 partial response (PR). Twenty-seven patients completed the planned two cycles of VIDL while four patients did not because three patients progressed during or after CCRT, and one patient is ongoing. The overall response rate of 27 patients completed VIDL was 92.6%, and two patients relapsed after the completion of VIDL chemotherapy. The major toxicity of VIDL was grade 3/4 leucopenia (85.1%), but there was no treatment-related mortality. The non-hematologic toxicity was tolerable, and the hepatic toxicity-associated with the use of L-asparaginase was frequent (55.5%). However, the majority of the hepatic toxicities were grade 1 or 2. Conclusion Concurrent chemo-radiotherapy followed by VIDL chemotherapy can be an effective treatment strategy with acceptable toxicity in stage I/II extranodal NK/T-Cell lymphoma of nasal cavity/nasopharynx. Disclosures: No relevant conflicts of interest to declare.

Preliminary Results Of Treatment Extranodal NK/T-Cell Lymphoma, Nasal Type Stage I-II AT K Hospital

2020 ◽  
Author(s):  
Linh Phan Van
Keyword(s):  
T Cell ◽  
Partial Response ◽  
Concurrent Chemoradiotherapy ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Female Ratio ◽  
Nasal Type ◽  
Results Of Treatment ◽  
Nk T Cell

Background: Extranodal NK/T-cell lymphoma, nasal type, is a rare subtype of non-Hodgkin lymphoma, origin from natural killer (NK) cells and T cells. This is a rare, fast-growing and poor prognosis disease. Currently there have been not many studies in Vietnam on this issue. We conduct this research with two objects: to describe characteristics of patients and evaluate premininary results of treatment extranodal NK/T cell lymphoma, nasal type, stage I to II at K hospital. Methods: Retrospective study. From January 2017 to June 2020, we enrolled 26 patients with extranodal NK/T cell lymphoma, nasal type, stage I to II. Patients were treated concurrent chemoradiotherapy with cisplatin, followed by 3 cycles of VIPD adjuvant regimen. Results: Patient characteristics: The average age was 43.2. Male/female ratio was 1.36. The most common symptoms were stuffy of nose 84.6%; runny nose 65.4%. Peripheral lymph nodes observed in 19.2%; 50% with B symptom. Staged I was dominated with 73.1%. Treatment results: Concurrent chemoradiotherapy phase: completed response was 26.9%, partial response 53.8% and progression disease 19.2%. At the end of treatment course, the overall response rate was 73% (including 61.5% completed response and 11.5% partial response), 26.9% cases with disease progression. Toxicity: Leukopenia was the most common toxicity (61.1%). Grade III and IV leukopenia were observed in 18.4%. Conclusions: Concurrent chemoradiotherapy followed by adjuvant VIPD regimen with stage I, II is effective regimen and acceptable toxicity.

The Efficacy of Bortezomib-CHOP In Patients with Advanced Stage T or NK/T Cell Lymphomas: The Results of Multicenter Phase II Study.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1791-1791 ◽  
Author(s):  
Seok Jin Kim ◽  
Hyeon-Seok Eom ◽  
Jin Seok Kim ◽  
Hye Jin Kang ◽  
Hyo Jung Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Advanced Stage ◽  
Chop Regimen ◽  
T Cell Lymphomas ◽  
Nk T Cell

Abstract Abstract 1791 Background Advanced stage T-cell or NK/T-cell lymphomas usually show aggressive clinical course and their treatment outcomes are worse than B-cell non-Hodgkin lymphoma. Furthermore, the optimal treatment regimen is not still established for these disease entities. At present, cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) regimen is still used as a primary treatment for advanced stage T or NK/T cell lymphomas although its efficacy is not satisfactory. Thus, more effective treatment regimen is required to improve treatment outcome. The incorporation of new targeted agents into CHOP regimen has been a widely used strategy to develop new regimen for the treatment of lymphoma. Bortezomib, a proteasome inhibitor approved for the use of treatment of multiple myeloma has been tried in many B-cell non-Hodgkin lymphomas. A recent in vitro study results showed that proteasome inhibitor could inhibit the growth of NK/T lymphoma cells. Based on these results, we designed a regimen combining CHOP with. Our previous phase I study determined the maximum tolerated dose of bortezomib as 1.6mg/m2 for combination with CHOP. Thus, we performed the phase II study to evaluate the efficacy of bortezomib plus CHOP chemotherapy. Methods We enrolled patients with newly diagnosed T or NK/T cell lymphoma. All patients were Ann Arbor stage III/IV and had adequate organ function. Patients received bortezomib on days 1 and 8 (weekly schedule, 1.6 mg/m2 per dose) in addition to 750 mg/m2 cyclophosphamide, 50 mg/m2 doxorubicin, 1.4 mg/m2 vincristine on day 1 and 100 mg/day prednisolone on days 1 to 5, every 3 weeks. Six cycles of therapy administered every 21 days were planned. All patients provided written informed consents and this trial was registered at www.ClinicalTrials.gov (NCT00374699). Results 46 patients were enrolled between April 2007 and August 2009. Peripheral T-cell lymphoma, unspecified (n=16) and extranodal NK/T cell lymphoma (n=10) were dominant subtypes while angioimmunoblastic T-cell lymphoma (n=8) and ALK-negative anaplastic large cell lymphoma (n=6) account for 30.4% of all patients. Five patients with cutaneous T-cell lymphoma and one hepatosplenic T-cell lymphoma were also recruited. The median age at diagnosis was 52 years (range 21 – 66 years). Serum LDH elevation (n = 28, 60.9%) and stage IV patients were dominant (n = 32, 69.6%). Thus, the International Prognostic Index risk was dominantly high or high-intermediate (n = 26, 56.5%). Complete response was achieved in 30 patients (65.2%) and partial response was 5 patients (10.9%). As a result, the overall response rate was 76.1%. The comparison of complete response rate based on the subtype demonstrated that the complete response rate of peripheral T-cell lymphoma, unspecified (12/19, 63.2%), angioimmunoblastic T-cell lymphoma (6/8, 75%), anaplastic large cell lymphoma (4/6, 66.7%) and cutaneous T-cell lymphoma (5/5, 100.0%) was better than extranodal NK/T cell lymphoma (3/10, 30.0%). Five patients with extranodal NK/T cell lymphoma progressed during the treatment with bortezomib and CHOP. The hematologic toxicity was the major toxicity of this regimen, thus, grade 3/4 leucopenia and febrile neutropenia were the most frequent toxicity. However, there was no treatment-related mortality. In addition, neurotoxicity was tolerable, so the majority of peripheral neurotoxicity was grade 1 or 2. Conclusion The combined treatment of bortezomib with CHOP is an effective regimen for advanced stage T-cell lymphomas with acceptable toxicity. However, it may not be efficient for advanced stage extranodal NK/T-cell lymphomas. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Phase Ib/IIa Trial of the Combination of Romidepsin, Lenalidomide and Carfilzomib in Patients with Relapsed/Refractory Lymphoma Shows Complete Responses in Relapsed and Refractory T-Cell Lymphomas

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2991-2991 ◽  
Author(s):  
Neha Mehta-Shah ◽  
Alison J Moskowitz ◽  
Matthew Lunning ◽  
Peggy Lynch ◽  
Mark Scheuerman ◽  
...  
Keyword(s):  
T Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Hematologic Toxicity ◽  
Advisory Committees ◽  
Grade 3

Abstract Background:Epigenetic manipulation and immunomodulation are therapeutic strategies in hematologic malignancies. In our previous study, the combination of romidepsin and lenalidomide demonstrated a 58% overall response rate, complete response rate of 11% and median event free survival was 16 weeks in patients (pts) with relapsed or refractory T-cell lymphoma. Given the potential synergy of proteasome inhibitors with histone deacetylase inhibitors and lenalidomide, we conducted a phase Ib/IIa study to evaluate the safety and toxicity of romidepsin and lenalidomide in combination with carfilzomib in pts with relapsed or refractory lymphoma. Here we report the safety, toxicity, and maximum tolerated dose (MTD) from the completed phase I portion of the study as well as the efficacy data from the completed T-cell lymphoma phase IIa cohort. Methods: The phase I portion evaluated toxicity and defined MTD. The clinicalactivity of the combination of romidepsin, lenalidomide, and carfilzomib was assessed in the phase I and lineage specific phase IIa cohorts. Romidepsin and carfilzomib were given IV on days 1, 8 and lenalidomide was given orally on days 1-14 of a 21-day cycle. A standard 3+3 dose escalation schema was followed: The starting dose was romidepsin 8 mg/m2,lenalidomide 15 mg, carfilzomib 36mg/m2. Dose-limiting toxicity (DLT) was defined in cycle 1 as ≥ grade 3 non-hematologic toxicity, grade 4 hematologic toxicity, grade ≥ 3 thrombocytopenia with bleeding, grade 3 hematologic toxicity resulting in a significant delay of treatment or inability to receive day 1 of cycle 2 due to continued drug related toxicity. Tumor response was based on disease-specific criteria.Pts could be treated until progression, intolerance, or response adequate to allow allogeneic transplantation. Results:20 pts were enrolled with 19 evaluable for toxicity (1 patient with T-cell lymphoma progressed prior to receipt of any study drug). 17 pts were treated for T-cell lymphoma (11 in the phase 1 portion and 6 in the phase IIa cohort): peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)-9, angioimmunoblastic T-cell lymphoma (AITL)-4 (one with concurrent diffuse large B-cell lymphoma-DLBCL), mycosis fungoides (MF)-2, transformed MF-1, extra-nodal NK/T-cell lymphoma (ENKTCL)-1. 3 pts in the phase 1 portion were treated for B-cell lymphoma: DLBCL-3. The T-cell lymphoma cohort is complete and efficacy data is reported here. Dose level 2 (romidepsin 8 mg/m2,lenalidomide 15 mg, carfilzomib 45mg/m2) exceeded the MTD with 2/6 DLTs: 1 pt with grade 3 thrombocytopenia resulting in treatment delay and 1 pt with grade 4 thrombocytopenia. There were no DLTs among 6 pts treated in dose level 1 (romidepsin 8 mg/m2,lenalidomide 15 mg, carfilzomib 36mg/m2) and dose level 1 was deemed the MTD. Grade 3-4 toxicities in >10% pts included neutropenia and thrombocytopenia. SAEs included: infection-3, progression of disease resulting in hospitalization-3, fever-2, febrile neutropenia-1, DVT-1, edema-1, dyspnea-1, atrial flutter-1, generalized weakness-1, and vomiting with diarrhea-1. Of the 16 pts with T-cell lymphoma evaluable for response, the overall response rate was 50% (8/16, 95% CI: 25 to 75%). The complete responses rate was 31% (5/16, 95% CI: 11 to 59%) and the partial response rate was 19% (3/16, 95% CI: 4 to 46%). Complete responses were seen in AITL (4/5) and PTCL-NOS (1/8) with 3 pts in CR proceeding to allogeneic stem cell transplantation. Partial responses were seen in PTCL-NOS-1, AITL-1, and transformed MF-1. In T-cell lymphoma, the median event free survival for all pts was 9.7 weeks (95% CI: 6.0 to NR) and for responders was not reached (95% CI: 15.0 to NR). The median time to response was 5.8 weeks. The median duration of response was 9.6 weeks (95% CI: 8.0 to NR). 3 pts underwent allogeneic transplantation following this therapy and another 2 pts with CR remain in continuous remission. Median duration of follow up was 20.4 weeks (range 3.4-40.9 weeks). Conclusions: The MTD dose for phase 2 study was identified as romidepsin 8mg/m2, lenalidomide 15mg and carfilzomib 36mg/m2. No unexpected toxicities have emerged. The preliminary overall and complete response rates of this regimen are promising in T-cell lymphoma, particularly in AITL, and warrants further study. An expansion cohort in B-cell lymphoma cohort is ongoing. Disclosures Moskowitz: Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy. Lunning:Gilead: Consultancy; Bristol-Myer-Squibb: Consultancy; AbbVie: Consultancy; Genentech: Consultancy; Juno: Consultancy; Pharmacyclics: Consultancy; TG Therapeutics: Consultancy; Spectrum: Consultancy; Celgene: Consultancy. Kumar:Celgene: Research Funding; Adaptive Biotechnologies: Research Funding; Seattle Genetics: Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria, Other: Scientific Advisory Board. Zelenetz:Gilead Sciences: Research Funding. Hamlin:Novartis: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Xencor: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Portola: Research Funding; Seattle Genetics: Research Funding; Molecular Templates: Research Funding. Noy:Pharmacyclics, LLC, an AbbVie Company: Other: travel, accommodations, expenses, Research Funding. Palomba:Pharmacyclics: Consultancy. Dogan:Seattle Genetics: Consultancy; Consulting Cancer Panel: Membership on an entity's Board of Directors or advisory committees; Cancer Genetics: Membership on an entity's Board of Directors or advisory committees; Peerview Institute: Consultancy. Horwitz:Bristol-Myers Squibb: Consultancy; Infinity: Consultancy, Research Funding; Celgene: Consultancy; Takeda: Consultancy, Research Funding; ADCT Therapeutics: Research Funding; Huya: Consultancy; Kyowa Hakka Kirin: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Spectrum: Consultancy, Research Funding.

scholarly journals Phase II trial of concurrent chemoradiotherapy with L-asparaginase and MIDLE chemotherapy for newly diagnosed stage I/II extranodal NK/T-cell lymphoma, nasal type (CISL-1008)

Oncotarget ◽  
2016 ◽  
Vol 7 (51) ◽  
pp. 85584-85591 ◽  
Author(s):  
Dok Hyun Yoon ◽  
Seok Jin Kim ◽  
Seong Hyun Jeong ◽  
Dong-Yeop Shin ◽  
Sung Hwa Bae ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Concurrent Chemoradiotherapy ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Stage I ◽  
Newly Diagnosed ◽  
Nasal Type ◽  
Nk T Cell

Phase I/II Study of Concurrent Chemoradiotherapy for Newly-Diagnosed, Localized Nasal NK/T-Cell Lymphoma: Results of a Phase I Portion of JCOG0211-DI.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2685-2685 ◽  
Author(s):  
Motoko Yamaguchi ◽  
Masahiko Oguchi ◽  
Kensei Tobinai ◽  
Nobuo Maseki ◽  
Takayo Suzuki ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
Concurrent Chemoradiotherapy ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Level 1 ◽  
Nk T Cell ◽  
Grade 3 ◽  
Level 2

Abstract Nasal NK/T-cell lymphoma is a rare lymphoid neoplasm, and its standard therapy has not been established. It is one of the Epstein-Barr virus (EBV) - associated lymphoid malignancies, and lymphoma cells express P-glycoprotein concerning multi-drug resistance (MDR) of the disease. Anthracycline-containing chemotherapy followed by radiotherapy (RT) has been established as the standard care for localized aggressive NHL; however this strategy is not effective for localized nasal NK/T-cell lymphoma. The 5-year overall survival rates of RT alone are only 30–40%. To explore a more effective treatment for newly-diagnosed localized nasal NK/T-cell lymphoma, we conducted a multicenter phase I/II study of concurrent chemoradiotherapy consisted of 50 Gy of RT and 3 courses of DeVIC chemotherapy [carboplatin (CBDCA) 300mg/m2 d1 IV, etoposide (ETP) 100mg/m2 d1-3 IV, ifosfamide (IFM) 1.5g/m2 d1-3 IV, dexamethasone (DMS) 40mg/body d1-3 IV; every 21 days]. DeVIC comprised of MDR-non-related agents and ETP that shows both in vitro and in vivo efficacy for NK-cell neoplasms, and is well-known to be effective for EBV-associated hemophagocytic syndrome. Pts with newlydiagnosed, localized (IE and contiguous IIE with cervical node involvement) diseases, 20–69 years of age and PS 0–2 were eligible. The protocol requests the CT based 2 or 3 dimensional RT planning that the volume with appropriate margin (2 cm) to gross tumor, entire nasal cavities and nasopharynx should be irradiated. In the phase I portion, a standard 3+3 design was used to evaluate dose-limiting toxicities (DLTs). The doses of RT and DMS were fixed. Two dose levels of CBDCA/ETP/IFM were evaluated: Level 1 (2/3-dose DeVIC) CBDCA 200mg/m2, ETP 67mg/m2, IFM 1.0g/m2 and Level 2 (100%-dose DeVIC). Enrolled 10 pts showed the following features: age 30–61 yrs (median 44.5), M:F=5:5, stage IE 6, stage IIE 4, B symptom(+) 4, elevated serum LDH 2, PS0 6, PS1 4. No treatment-related death occurred, and no grade 4 non-hematologic toxicities other than transient hypokalemia were observed. Grade 4 neutropenia and grade 3 mucositis due to RT were common. At Level 2, grade 4 leukopenia/anemia/thrombocytopenia and grade 3 infection were more frequent than Level 1. In summary, at Level 1, 1 pt developed PD before evaluation of DLT. Remaining 3 pts did not develop DLT. At Level 2, 4 out of 6 pts developed DLT. Thus, we decided to select the Level 1 for the subsequent phase II portion. Of all 10 enrolled pts, 7 achieved CR, 2 PD, and 1 not evaluable. Of note, all 10 pts achieved local control. Our results suggest that concurrent chemoradiotherapy using MDR-non-related agents and ETP is a promising treatment strategy for localized nasal NK/T-cell lymphoma. Feasibility and efficacy of Level 1 will be evaluated further in the phase II portion.

scholarly journals A Phase II Study of MESA Chemotherapy for Newly Diagnosed, Relapsed or Refractory Extranodal Natural Killer (NK)/T-Cell Lymphoma, Nasal Type: A Multicenter Trial of Northern-West of China

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3945-3945
Author(s):  
Rong Liang ◽  
Gao Guangxun ◽  
Chen Jie Ping ◽  
Jishi Wang ◽  
Xiao min Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Nasal Type ◽  
Nk T Cell ◽  
Grade 3

Abstract Purpose/Background: The nasal type of extranodal natural killer NK/T-cell lymphoma (NKTCL) is a rare aggressive lymphoma with poor prognosis. There is currently no standard treatment. To explore a more effective and feasible treatment for newly diagnosed, relapsed, or refractory NKTCL, we conducted a phase II study of the steroid (Methotrexate, etoposide, dexamethasone, Polyehylene glycol-asparaginase, MESA) regimen and investigated its efficacy and toxicity. Patients and Methods: Patients with newly diagnosed, relapsed, or refractory disease were treated in 5 medical centers. The performance status of 0 to 2 were eligible. At least three cycles of MESA chemotherapy + radiotherapy (RT) + three cycles of MESA chemotherapy were administered as the protocol treatment. The primary endpoints were the complete response (CR) rate, partial response (PR), the overall response rate (ORR), and toxicities. Secondary endpoints were overall survival (OS) and progression-free survival (PFS) rate. Results: A total of 46 eligible patients were enrolled. The median age was 46.1 years (range, 16 to 54 years), and the male: female ratio was 36:10. Among the 35 new diagnosed patients with first-line MESA treatment, the CR/PR at 1 cycle, 2 cycle and 3 cycle was 42.4%/55.9%, 46.9%/50% and 64%/32%, respectively; The ORR was 97.1%, 93.9% and 92.3%. Among 11 relapsed or refractory patients with second-line MESA, the CR/PR at 1 cycle, 2 cycle and 3 cycle was 9.1%/90.9%, 20%/80% and 22.2%/55.6%, respectively; The ORR was 100%, 90.9% and 77.8%. For 35 new diagnosed patients , the 0.5 year, 1 year, 1.5 year, 2 year-OS/PFS was 88.6%/75%, 90%/80%, 92.9%/92.9%, 100%/85.7%, respectively. For 11 relapsed or refractory patients, the 0.5 year, 1 year, 1.5 year, 2 year-OS/PFS was 100%/2.17%, 91.7%/8.7%, 40%/4.3%, 0%/0%, respectively. For 8 advance (IV stage newly diagnosed) NKTCL and 8 relapsed/refractory NKTCL, CR rate was 37.5%(n=6) after 3 cycle MESA, which was less than that of other studies such as SMILE and GELA/GOELAMS. However, PR rate 56.3%(n=9),ORR 93.8%(n=15) and 2y OS rate 81.3%(n=13) were higher than that of other studies. It was showed that different stages had different CR rate and PFS rate. However, the OS had no difference. it was also showed that patients with Ki67≥60% had lower 3 cycle-CR rate and 1 year OS/PFS rate than that of Ki67<60%. Grade 1 and 2 toxicities were frequent during MESA treatment. 4 patients developed grade1/2hypofibrinogenemia. 6 patients experienced grade 3 leukopenia or thrombocytopenia and 3 patients suffered from severe infection. 13 patients had a grade 1/2 abnormal liver function and 1 patient had grade 3 without delay in chemotherapy. Pegaspargase was well tolerated in all of them. No patient developed grade 4 adverse effects. There were no treatment-related deaths. Conclusion: The initial results of MESA chemotherapy for aggressive newly diagnosed, relapsed or refractory NKTCL this type of lymphoma were very encouraging with high effect and safety. These results will require further investigation in larger prospective trials. Disclosures No relevant conflicts of interest to declare.

The efficacy of PEG-Asp-argase-based chemotherapy for nasal-type extranodal NK/T-cell lymphoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e19504-e19504
Author(s):  
Jing-Yun Wen ◽  
Mai Li ◽  
Xing Li ◽  
Qu Lin ◽  
Min Dong ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Invasive Disease ◽  
Bone Marrow Suppression ◽  
T Cell Lymphoma ◽  
Chop Regimen ◽  
Nasal Type ◽  
Nk T Cell

e19504 Background: Nasal-type extranodal NK/T-cell lymphoma (ENKL) is a highly invasive disease with quite poor prognosis.Pegaspargase (PEG-Asp) displays a similar anti-cancer mechanism as that of L-asparaginase (L-ASP), but exhibits lighter antigenicity. The aim of the present research was to evaluate efficacy and safty of PEG-Asp-based regimen in ENKL. Methods: Data were collected from 23 patients with histologically confirmed ENKL who were admitted to the Third Affiliated Hospital of Sun Yat-Sen University from January 2009 to March 2012. Each patient received PEG-Asp 2500 IU/m2/IM on day 1 of each 21-day chemo-cycle. Among them, 8 received combination chemotherapy with CHOP regimen, 11 with EPOCH, and 4 with a CHOP-like regimen (CHOP + bleomycin). The CHOP regimen consisted of cyclophosphamide 750mg/m2, IV (day 1), pirarubicin 40mg/m2, IV (day 1), vincristine 1.4 mg/m2, IV (day 1), and prednisone 100mg, oral (days 1- 5). The EPOCH regimen consisted of etoposide 50mg/m2, epidoxorubicin 12 mg/m2 and vincristine 0.4mg/m2 dissolved in 500mL saline and administered as a continuous IV drip for 24 hours on days 1- 4. Cyclophosphamide 750mg/m2, IV (day 5) and prednisone 60mg/m2, oral (days 1-5), were also administered. In the CHOP-like regimen, bleomycin 15mg was added on days 1-3. Stage I-II patients received local radiotherapy after the chemotherapy. Results: The patients received the PEG-Asp-based chemotherapy for 2-5 cycles (median, 4 cycles). Eleven (47.8%) achieved complete response (CR), and the overall response rate (ORR) was 82.6%. The median time to progression (TTP) was 5 months (range, 2-6 months) and the median OS was 16 months (range, 5-38 months). The 1-year and 2-year survival rate were 82.6% (19/23) and 56.5% (13/23) , respectively. A minor glutamic-pyruvic transaminase (GPT) elevation was observed in 3 patients (13.0%), slight decrease of albumin in 3 (13.0%), reduced fibrinogen level in 2 (8.7%), grade I-II WBC bone marrow suppression in 8 (34.8%), and grade III-IV WBC bone marrow suppression in 3 (13.0%). No allergic incidences were witnessed. Conclusions: Our results suggested PEG-Asp-based chemotherapy presented potential effects in treating nasal-type ENKL with acceptable side effects profile.

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