A Prospective Phase II Trial of An L-Asparaginase Containing Regimen in Patients with Refractory or Relapsing Extra Nodal NK/T-Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 579-579 ◽  
Author(s):  
Arnaud Jaccard ◽  
Nathalie Gachard ◽  
Paul Coppo ◽  
Franck Morschhauser ◽  
Lionel Galicier ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Nasal Type ◽  
Prospective Phase ◽  
Nk T Cell

Abstract Extra nodal NK/T-cell lymphoma, nasal type, is an EBV-related highly aggressive disease with a poor outcome, especially when disseminated or recurrent after radiotherapy. L-Asparaginase seems to have a particular efficacy in this disease (Jaccard, 2008, Ann oncol). Nineteen patients with relapsing or refractory extra nodal NK/T-Cell Lymphoma, nasal type, were included in a multicentric prospective phase II trial using the Aspametdex regimen (E coli-L-asparaginase (Kidrolase®) 6000 UI/m2 IM at day 2,4,6,8, methotrexate 3 gr/m2 at day 1 and dexamethasone 40 mg at day 1 to 4 with 3 weeks cycles). Patients below 65 years of age and with a good performance status received 3 cycles and, in case of good response, an intensive treatment with the BEAM regimen and stem cell rescue. Other patients received up to 6 cycles of the Aspametdex protocol. Patients with localized disease received irradiation if not performed before inclusion. The histology was centrally reviewed and EBV viremia was regularly and centrally monitored. The response after 3 cycles was the primary end point. There were 14 men and 4 women (1 patient was excluded after pathologic review), median age was 59.5 (45 to 76), 7 were primary refractory, 11 were in relapse, 6 were in stage IV. Median number of cycles was 3 (1 to 6). Three patients who had an allergic reaction with L-asparaginase received further courses of Erwinia-asparaginase (Erwiniase®) (n= 3). Toxicity related to L-asparaginase was mild, mainly brief leucopenia (n=2), elevation of alanine aminotransferase (n=2) and venous thrombosis (n=1). Response was documented in 17/18 patients, 10 patients were in complete remission (CR) after treatment with L-asparaginase and 5 patients in partial remission. Five patients died of unrelated causes (n=1) or progression of disease (n=4). Thirteen patients are still alive with a median follow-up of 8 months (1 to 29), 5 responding patients progressed at 4, 5, 8, 8 and 22 months after treatment. Six patients are in persistent CR, 2 of these patients had received high dose therapy with autologous stem cell transplant and 1 patient received irradiation after L-asparaginase treatment. These data confirm the excellent activity of L-asparaginase-containing regimens in extranodal NK/T-cell lymphoma. This must be known because of the very poor prognosis of patients with disseminated or relapsing disease with conventional chemotherapy. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma should be tested in prospective trials.

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 II study of SMILE chemotherapy for newly-diagnosed stage IV, relapsed or refractory extranodal NK/T-cell lymphoma, nasal type: NKTSG study.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 8044-8044 ◽  
Author(s):  
M. Yamaguchi ◽  
Y. Kwong ◽  
Y. Maeda ◽  
C. Hashimoto ◽  
W. Kim ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Stage Iv ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Nasal Type ◽  
Nk T Cell

L-Asparaginase in the Treatment of Relapsing Nasal/Nasal Type NK-T-Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4598-4598
Author(s):  
Arnaud Jaccard ◽  
Felipe Suarez ◽  
Jean-Marc Zini ◽  
Pascal Turlure ◽  
Franck Trimoreau ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Gastrointestinal Tract ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Nasal Type ◽  
Western Countries ◽  
Nk T Cell

Abstract Nasal/nasal type NK-T-cell lymphoma is a rare and severe type of non Hodgkin’s lymphoma (NHL) more frequent in asia than in western countries. When localised, radiotherapy seems to be the best treatment. When radiotherapy cannot be used because of dissemination or relapse, chemotherapy protocols used for other types of NHL give poor results. Recently some papers from China and Japan, (Yong W et al: L-asparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int J Hematol. 2003 Aug;78(2):163–7), reported the efficacy of a drug: L-asparaginase, usually used to treat acute lymphoblastic leukemia. Few patients have been treated in Asia and no patient from western countries have been reported. We used this drug in 3 french centers to treat 7 patients with relapsed nasal/nasal type NK-T-cell lymphoma. There were 4 men and 3 women, median age was 52 (39 to 81), the primary site of disease was the nasal cavity in 3 patients, the nasopharynx in 2, the gastrointestinal tract in 1 and the bone marrow in 1. Pathological diagnosis was confirmed by biopsy, showing typical aspect of necrosis and angioinvasion. Tumoral cells were usually CD20 negative, SCD3 positive, CD56 positive. EBV was found by in situ hybridisation in all but one case. When L-asparaginase was given 5 patients were refractory to CHOP and/or DHAP regimen, 5 patients were in stage IV with bone marrow involvment (n=2), cerebral involvment (n=2), gastrointestinal tract involvment (n=1). Hemophagocytosis was seen in 3 patients with typical biological anomalies. L-asparaginase 6000 UI / m2 (1 to 3 courses) was given for 5 to 10 days associated with Dexamethasone 40 mg for 4 days (n=4), methotrexate 3 gr/m2 (n=1) or velbe 6 mg (n=1). 2 patients who had a severe anaphylactic reaction with L-asparaginase received further courses of PEG-asparaginase. Treatment efficacy was evident in all patients with 4 patients in complete remission (CR) and 3 patients in partial remission (PR) after treatment with L-asparaginase. 2 patients died, one of acute GVH after allotransplantation and a second 1 month after the second course of L-asparaginase, probably of pulmonary embolism. Apart from this case toxicity related to L-asparaginase was mild, mainly brief leucopenia and elevation of alanine aminotransferase. With antithrombine III transfusions when its level was below 60% no other thrombotic event was noted. 5 patients are still alive with a median follow-up of 7 months (3 to 13), 4 patients are in persistent CR, 2 had received high dose therapy with autologous stem cell transplant. The efficacy of L-asparaginase to treat nasal and nasal type NK-T-cell lymphoma must be known because of the very poor prognosis of relapsing patients with conventionnal chemotherapy. Prospective studies using L-asparaginase for de novo patients are warranted.

L-Asparaginase Monotherapy in Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma, Nasal Type: Results of A Phase II Study.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2730-2730
Author(s):  
Ye Guo ◽  
Xuejun Ma ◽  
Zuguang Xia ◽  
Kai Xue ◽  
Qunling Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Single Agent ◽  
T Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Nasal Type ◽  
Nk T Cell

Abstract Abstract 2730 Introduction: Recently, L-asparaginase-based combination chemotherapy was found to be effective in salvage treatment in patients with relapsed or refractory extranodal NK/T-cell lymphoma, nasal type. To explore the single-agent activity of L-asparaginase, we conducted a single-institute, prospective phase II study. Methods: Patients with relapsed or refractory extranodal NK/T-cell lymphoma, nasal type were eligible for enrollment regardless of prior treatment. L-asparaginase monotherapy (6000 U/m2 on days 1 to 7) was administered as the protocol treatment and repeated every 3 weeks for at most 8 cycles. For responding patients, the decision to proceed with hematopoietic stem-cell transplantation was made at the discretion of treating physicians. The primary endpoint was the best objective response after L-asparaginase. Results: A total of 40 patients were enrolled and treated with L-asparaginase for a median of 5 cycles (range, 1 – 8). The patient characteristics were shown in Table 1. Half of the patients had stage IV disease at enrollment and the vast majority (18 patients) presented with disseminated cutaneous and soft-tissue involvement. Thirty-seven patients (92.5%) had prior exposure to systemic chemotherapy and 14 of them (37.8%) received more than 1 line. The overall response rate was 82.5%. The complete response (CR) and partial response (PR) rates were 40% and 42.5%, respectively. The incidence of adverse events was shown in Table 2. In short, anemia, neutropenia, hypoalbuminemia, nausea and liver-related disorders were common toxicities, which were usually mild and manageable. No grade 4 adverse events and treatment-related mortality were observed. Five patients (12.5%) developed allergic reaction to L-asparaginase and 3 of them had to withdraw from the study since L-asparaginase re-challenge with prophylactic antiallergic agents was unsuccessful. After a median follow-up time of 31.6 months (range, 21.9 – 41.3), the median progression-free survival (PFS) was 12.8 months and median overall survival (OS) was not reached. Response status (CR, PR or no response) after L-asparaginase had a significant impact on either PFS (Figure 1) or OS (Figure 2). Moreover, its prognostic value was confirmed in the multivariate analysis. Conclusions: L-asparaginase demonstrated a high single-agent activity in salvage setting for patients with extranodal NK/T-cell lymphoma, nasal type. The first-line L-asparaginase-containing chemotherapy regimen warrants urgent investigation. Disclosures: Off Label Use: L-asparaginase, which was used in our study for NK/T-cell lymphoma, is approved to treat acute lymphocytic leukemia by US and Chinese FDA.

A phase II trial of bevacizumab-GemAOD regimen for newly diagnosed extranodal NK/T cell lymphoma.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 7564-7564
Author(s):  
Zhiming Li ◽  
Yu Wang ◽  
Jia Jia Huang ◽  
Tian Xiao Gao ◽  
Ke Wu ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Nk T Cell

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.

Phase II/III randomized trial of CID-ATT with radiotherapy compared with CHOP with radiotherapy as first-line treatment for previously untreated early staging extranodal NK/T-cell lymphoma, nasal type (ENKL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8508-8508 ◽  
Author(s):  
Tongyu Lin ◽  
He Huang ◽  
Chao Yong Liang ◽  
Chengcheng Guo ◽  
Ying Tian ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Line Treatment ◽  
First Line ◽  
Chop Regimen ◽  
Nasal Type ◽  
Nk T Cell ◽  
First Line Treatment

8508 Background: Extranodal NK/T cell lymphoma, nasal type (ENKL) is more prevalent in Asia and has worse prognosis than B-NHL. No therapeutic strategy is currently identified for ENKL. This phase II/III study was undertaken to compare CHOP-B/IMVD/DHAP-Alternating Triple Therapy (CID-ATT) and standard CHOP regimen as first-line treatment prospectively. Methods:109 patients (pts) initially diagnosed as ENKL (16-70 ys old) with Ann Abor Stage I to II were randomized to receive CID-ATT or CHOP regimen from Jan 2006 to Jan 2012. CID-ATT alternated among CHOP-B, IMVD, and DHAP, given in alternating sequence for a total of 6 courses (2 circle). Involved field radiation was administered after 6 courses(2 circle) of CID-ATT regimen or 6 cycles of CHOP regimen. All pts received prophylactic granulocyte colony-stimulating factor, interleukin-11and thrombopoietin for each DHAP cycle. Results: 109 pts were evaluable (54CID-ATT; 55 CHOP). With a median follow-up of 40.3months,OS and PFS was significantly prolonged with CID-ATT compared with CHOP (1yOS :80.2% vs 78.6%, 3yOS:68.0% vs 42.3%, 5yOS: 64.2% vs 34.5%,P=0.023; 1yPFS: 74.9% vs 59.6%, 3yPFS:60.5% vs 32.0%, 5yPFS: 60.5% vs 32.0% ; P=0.016). Compared to CHOP group, CID-ATT group has a much higher complete remission rate (CID-ATT:47/54,87.0 % vs CHOP:29/55,52.7%, P<0.001). The survivals for pts who achieved CR after One circle (3 courses) were significantly better than those who were in non-CR group.(5yOS: CR group in ATT:75.3%, non-CR group in ATT:51.5%, CR group in CHOP:39.3%, non-CR group in CHOP:31.0%; P=0.003). No treatment related death was observed, although Grade III/IV neutropenia (30/54,55.6%) and thrombocytopenia (33/54,61.1%) were observed in CID-ATT regimen, especially in DHAP cycle. Conclusions: Our study has demonstrated that the CID-ATT regimen as an optimal first-line therapy achieved promising clinical activity with safe and tolerated toxicity under close monitoring and good supportive care of untreated early staging ENKL pts. CR of induce chemotherapy following radiotherapy is very important for ENKL survival. Clinical trial information: CSWOG0002.

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