Marqibo (Vincristine Sulfate Liposomes Injection (OPTISOME™) Demonstrates Activity in Patients with Relapsed and Refractory Peripheral T-Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4466-4466
Author(s):  
M. Alma Rodriguez ◽  
Jane N. Winter ◽  
Biao Lu ◽  
Gary Huang ◽  
Gavin S. Choy ◽  
...  
Keyword(s):  
Adverse Event ◽  
T Cell ◽  
Cell Lymphoma ◽  
International Workshop ◽  
Objective Response ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Low Grade ◽  
Peripheral T Cell Lymphoma ◽  
Best Response

Abstract Introduction: New and more effective agents are needed to improve treatment outcomes for patients with relapsed and refractory peripheral T-cell lymphoma (PTCL). Marqibo is a novel formulation of vincristine (VCR) encapsulated in sphingomyelin/cholesterol liposome called OPTISOME. In preclinical studies, OPTISOME technology has been shown to provide targeted, increased, and sustained delivery of VCR to tumor cells compared to non-encapsulated VCR or VCR encapsulated in conventional liposomes. Methods: PTCL patients from two multi-center phase 2 studies of Marqibo in relapsed and refractory lymphoid malignancies are integrated for safety and efficacy evaluation. In both studies, Marqibo (2.0 mg/m2 without dose capping IV over 60 minutes) was administered every 14 days for up to 12 cycles or until toxicity or progressive disease was observed. The primary efficacy endpoint of the 2 studies was the objective response rate (ORR) defined as the percentage of patients whose best response was complete response (CR), complete response unconfirmed, or partial response (PR). Best response was determined according to the International Workshop Response Criteria. Secondary endpoints included adverse event evaluation, time to progression (TTP) and overall survival (OS). Results: Six (3M/3F) patients diagnosed with PTCL received at least one dose of Marqibo. At baseline, the median age was 59 years (range, 34–86). All six patients had aggressive disease and most were heavily pretreated. The median number of prior lines of chemotherapy and immunotherapy regimens was 3 (range, 1–6) and four patients (66.7%) had received prior autologous bone marrow transplant. All patients had prior exposure to neurotoxic therapy: platinum compounds (33.3%), taxanes (16.7%) and VCR (100%). All patients had achieved a CR or PR to their frontline therapy and 50% (3/6) had achieved a CR or PR to their last line of therapy prior to receiving Marqibo. Patients received a median of 4 cycles of Marqibo (range, 1–9). Median cumulative dose of Marqibo was 7 mg/m2 (range, 2–17.4). The most commonly reported adverse event was peripheral sensory neuropathy (3 of 6 patients) and all of Grade 1 severity. Three patients had PR, 1 patient had stable disease, 1 patient experienced disease progression, and 1 patient was unevaluable. Median OS and TTP were 194 and 70 days, respectively. Conclusions: These preliminary results suggest encouraging activity and tolerability of Marqibo in heavily pre-treated relapsed and refractory PTCL patients. Given the high proportion of exposure to neurotoxic agents preceding Marqibo, the low grade neurotoxicity noted following Marqibo is a favorable finding.

Results From a Pivotal, Open-Label, Phase II Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma After Prior Systemic Therapy

2012 ◽  
Vol 30 (6) ◽  
pp. 631-636 ◽  
Author(s):  
Bertrand Coiffier ◽  
Barbara Pro ◽  
H. Miles Prince ◽  
Francine Foss ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Systemic Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Prior Systemic Therapy

Purpose Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Patients and Methods Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days. The primary end point was the rate of complete response/unconfirmed complete response (CR/CRu) as assessed by an independent review committee. Results Of the 131 patients enrolled, 130 had histologically confirmed PTCL by central review. The median number of prior systemic therapies was two (range, one to eight). The objective response rate was 25% (33 of 130), including 15% (19 of 130) with CR/CRu. Patient characteristics, prior stem-cell transplantation, number or type of prior therapies, or response to last prior therapy did not have an impact on response rate. The median duration of response was 17 months, with the longest response ongoing at 34+ months. Of the 19 patients who achieved CR/CRu, 17 (89%) had not experienced disease progression at a median follow-up of 13.4 months. The most common grade ≥ 3 adverse events were thrombocytopenia (24%), neutropenia (20%), and infections (all types, 19%). Conclusion Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.

scholarly journals Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi

2021 ◽  
Vol 11 ◽  
Author(s):  
Laura Ballotta ◽  
Pier Luigi Zinzani ◽  
Stefano Pileri ◽  
Riccardo Bruna ◽  
Monica Tani ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Clinical Trial Registration ◽  
Prospective Phase ◽  
Bcl2 Protein

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified.Clinical Trial Registrationwww.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).

Peripheral T cell lymphoma.

1987 ◽  
Vol 5 (5) ◽  
pp. 750-755 ◽  
Author(s):  
R Liang ◽  
D Todd ◽  
T K Chan ◽  
K L Wong ◽  
F Ho ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Complete Response ◽  
Small Sample ◽  
T Cell Lymphoma ◽  
Chinese Patients ◽  
Peripheral T Cell Lymphoma ◽  
Small Sample Sizes

Thirty-one Chinese patients with peripheral T cell lymphoma (PTCL) were reviewed. Using the modified Japanese Lymphoma Group classification, there were nine (29%) of the pleomorphic type, 16 (52%) immunoblastic lymphadenopathy (IBL)-like, two (7%) T-zone lymphoma, and one (3%) Lennert's lymphoepithelioid type. Three (9%) were not classifiable. All were positive for T11 (E rosette receptor antigen). Fifty-four percent (15 of 28) were positive predominantly for T4 (helper T cell) and 46% (13/28) for T8 (suppressor T cell). The median age of the patients was 57 years. They usually presented with advanced disease, and while extranodal involvement was common, CNS disease was not seen. The IBL-like type was associated with a positive Coombs' test and polyclonal hypergammaglobulinemia. Five of the nine pleomorphic type were checked for antibody to HTLV-I virus and all were negative. PTCL was associated with poor prognosis, which was not influenced by the histologic subtypes and the T4/T8 phenotypes. The complete response rate of 13 consecutive patients who received the BACOP (bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone) L17M regimen was significantly better than the 16 historic controls who received other less-intensive regiments, 84% v 19% (P less than .01). The relapse rate was also significantly lower, 9% v 100% (P less than .001). There appeared to be an improvement in the disease-free survival (DFS) (80% v 0% at 18 months), as well as the overall survival (60% v 36% at 18 months), but the differences did not reach statistical significance due to small sample sizes.

Cutaneous Toxicity Associated with Pralatrexate in Cutaneous and Peripheral T-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3660-3660 ◽  
Author(s):  
Terri L. Parker ◽  
Lisa Barbarotta ◽  
Michael Girardi ◽  
Francine M. Foss
Keyword(s):  
Adverse Event ◽  
Data Analysis ◽  
T Cell ◽  
Cell Lymphoma ◽  
Median Number ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Cutaneous Toxicity ◽  
Off Label

Abstract Abstract 3660 Background: Pralatrexate is a folate analogue metabolic inhibitor that is approved for the treatment of relapsed or refractory peripheral T-cell lymphoma (PTCL) (O'Connor, O.A. et al. JCO. 2011 29: 1181–1189). More recently, pralatrexate has been investigated for the treatment of relapsed or refractory cutaneous T-cell lymphoma (CTCL) (Horowitz, S.M. et al. Blood. 2012 119: 4115–4122). The most common adverse event (AE) observed with pralatrexate has been mucositis with other reported AEs consisting of fatigue, nausea, and cutaneous toxicity. Methods: We retrospectively analyzed the data of 22 patients who had received pralatrexate for a diagnosis of either PTCL or CTCL at our institution since 2010 in order to determine the incidence of cutaneous toxicity. Results: Of the 22 patients, 4 had a diagnosis of PTCL, 18 had CTCL. In the PTCL cohort, the median age was 66.5 with the median number of prior treatments (nonsystemic and systemic) being 2.75. One patient (25%) developed cutaneous toxicity which resulted in death. A skin biopsy revealed toxic erythema of chemotherapy and the skin lesions progressed to bullae and moist desquamation. In the CTCL cohort, the median age was 60 with the median number of treatments being 5. A total of 14 patients (78%) developed cutaneous toxicity. The toxicity included worsening erythema, skin breakdown, ulceration, and pain at the CTCL lesion sites. The majority of patients (n= 10; 71%) developed the toxicity following cycle 1 week 1 of treatment. The development of cutaneous toxicity was seen in 8 patients at a dose of 15mg/m2, in 3 patients at a dose of 10mg/m2, and in 2 patients who underwent dose escalations to 17.5mg/m2 and 20mg/m2respectively. Of those patients who developed cutaneous toxicity, 8 (57%) required the pralatrexate to be held and 2 patients (14%) required hospitalization and treatment with intravenous antibiotics for superimposed skin infection. The cutaneous toxicity observed was not associated with any other adverse event. Seven patients (39%) in the entire CTCL cohort developed grade I/II mucositis and 3 (17%) developed grade I diarrhea. In 7 patients (50%) the pralatrexate was restarted at a lower dose, 3 patients were changed to an every other week dosing schedule, and 2 patients continued on pralatrexate with no change following resolution of their symptoms. Only 2 patients were not continued on pralatrexate following the cutaneous toxicity. In all 12 patients who were retreated with pralatrexate, cutaneous toxicity did not reoccur and the dose was able to be escalated. At the time of data analysis, 7 patients remained on treatment with pralatrexate while the remainder had discontinued therapy secondary to disease progression. Conclusions: In this retrospective review, a high incidence of cutaneous toxicity was seen in CTCL patients who were treated with pralatrexate. The cutaneous toxicity might be interpreted as a “skin flare” since it may be concentrated at sites of CTCL lesions. The majority of patients developed the toxicity with the first dose and were able to continue on pralatrexate at a lower dose with eventual dose escalation. Based on data analysis, the “skin flare” is not dose dependent or associated with disease response. Disclosures: Off Label Use: Pralatrexate is FDA approved for the treatment of relapsed or refractory peripheral T-cell lymphoma. Our abstract discusses its use, specifically the cutaneous toxicity observed, in both peripheral and cutaneous T-cell lymphoma. The use of pralatrexate in relapsed or refractory cutaneous T-cell lymphoma is off-label. Barbarotta:Genentech: Speakers Bureau; Allos: Speakers Bureau. Foss:Seattle Genetics: Consultancy; Celgene: Consultancy; Eisai: Consultancy; Celgene: Study Grant, Study Grant Other; Merck: Study Grant, Study Grant Other; Allos: Consultancy.

scholarly journals Pralatrexate in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results From the Pivotal PROPEL Study

2011 ◽  
Vol 29 (9) ◽  
pp. 1182-1189 ◽  
Author(s):  
Owen A. O'Connor ◽  
Barbara Pro ◽  
Lauren Pinter-Brown ◽  
Nancy Bartlett ◽  
Leslie Popplewell ◽  
...  
Keyword(s):  
T Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
International Workshop ◽  
Progression Free Survival ◽  
Median Number ◽  
T Cell Lymphoma ◽  
Cell Transplant ◽  
Peripheral T Cell Lymphoma ◽  
Prior Therapy

Purpose Peripheral T-cell lymphoma (PTCL) is a poor prognosis subtype of non-Hodgkin's lymphoma with no accepted standard of care. This study evaluated the efficacy and tolerability of pralatrexate, a novel antifolate with promising activity. Patients and Methods Patients with independently confirmed PTCL who progressed following ≥ 1 line of prior therapy received pralatrexate intravenously at 30 mg/m2/wk for 6 weeks in 7-week cycles. Primary assessment of response was made by independent central review using the International Workshop Criteria. The primary end point was overall response rate. Secondary end points included duration of response, progression-free survival (PFS), and overall survival (OS). Results Of 115 patients enrolled, 111 were treated with pralatrexate. The median number of prior systemic therapies was three (range, 1 to 12). The response rate in 109 evaluable patients was 29% (32 of 109), including 12 complete responses (11%) and 20 partial responses (18%), with a median DoR of 10.1 months. Median PFS and OS were 3.5 and 14.5 months, respectively. The most common grade 3/4 adverse events were thrombocytopenia (32%), mucositis (22%), neutropenia (22%), and anemia (18%). Conclusion To our knowledge, PROPEL (Pralatrexate in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma) is the largest prospective study conducted in patients with relapsed or refractory PTCL. Pralatrexate induced durable responses in relapsed or refractory PTCL irrespective of age, histologic subtypes, amount of prior therapy, prior methotrexate, and prior autologous stem-cell transplant. These data formed the basis for the US Food and Drug Administration approval of pralatrexate, the first drug approved for this disease.

Alemtuzumab and DHAP (A-DHAP) Is An Effective Salvage Therapy for Peripheral T-Cell Lymphoma, Unspecified: Interim Results of a Phase II Prospective Multicenter Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5002-5002
Author(s):  
Seok Jin Kim ◽  
Kihyun Kim ◽  
Byung Soo Kim ◽  
Cheolwon Suh ◽  
Won Seog Kim
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Cell Count ◽  
Response Rate ◽  
Chemotherapy Regimen ◽  
Cell Lymphoma ◽  
Objective Response ◽  
T Cell Lymphoma ◽  
Prospective Multicenter Study ◽  
Peripheral T Cell Lymphoma

Abstract Purpose: The prognosis for relapsed or refractory peripheral T-cell lymphomas (PTCLs) is extremely poor, and there is still no consensus on the optimal salvage therapy. Alemtuzumab (Campath-1H®, Bayer-Schering, Berlin, Germany) is a humanized immunoglobulin G1 anti-CD52 monoclonal antibody. Considering the expression of CD52 antigen on the surface of T-cell lymphoma cells, alemtuzumab could be a suitable agent for the treatment of PTCLs. A previous pilot study showed the efficacy of alemtuzumab as a single agent for patients with relapsed or refractory PTCLs. Thus, we designed a new chemotherapy regimen, A-DHAP, consisting of alemtuzumab and DHAP (dexamethasone, cisplatin, and cytarabine) to augment the efficacy of alemtuzumab against PTCLs. Herein, we report the interim results of phase II prospective multicenter study using the A-DHAP regimen in patients with relapsed or refractory PTCLs. Patients and Methods: We enrolled 16 patients between the ages of 18 and 65 years who had histologically confirmed PTCLs, excluding ALK-positive anaplastic large cell lymphoma. Patients were required to have failed primary treatments such as anthracycline-containing regimens. Failure was defined as a relapse from previous confirmed complete response (CR) or progress during treatment. Each patient received DHAP plus an escalated dosage of alemtuzumab (10 mg on day -1 and 30 mg on day 1 and 2) every 3 weeks for up to 3 cycles. Responders then received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Results: At relapse or progression after previous therapy, 13 patients presented as stage III or IV (81.3%). However, 11 patients belonged to low or low-intermediate IPI (international prognostic index) risk as they were less than 60 years old, had normal serum LDH and good performance status. Peripheral T-cell lymphoma, unspecified (PTCL-U) and extranodal NK/T cell lymphoma, nasal type (ENKTCL) were the dominant histological subtypes (14/16, 87.6%). The median treatment was 2 cycles (range 1–3 cycles). Seven patients completed the planned 3 cycles of A-DHAP. Eight patients showed an objective response including four CR and four PR, while seven patients showed PD (Progressive disease), and one patient had SD (Stable disease) after the 3rd cycle. Thus, the objective response rate was 50.0% (8 of 16 patients). When we analyzed the response according to the histological type, the objective response rate was much higher for PTCL-U (85.7%: 3 CR, 3 PR) than for ENKTCL (14.3%, 1 PR). Seven patients could receive autologous stem cell transplantation (ASCT); five patients after objective response and two patients after other salvage treatments. The median CD34+ cell count was more than 3.79×106/kg (range, 2.30 – 5.90×106/kg), and there was no engraftment failure. However, one patient could not receive ASCT because the yield of CD34+ cell count was less than the minimal requirement (2.00×106/kg) although his complete blood cell count was within normal range after the completion of three cycles of A-DHAP chemotherapy. The median overall survival (OS) after enrollment in the study was 6.0 months (95% confidence interval 3.51–8.49 months). Responders to A-DHAP showed a better OS than non-responders (P = 0.038). The most frequent side effects were grade 3/4 leukopenia and infectious complications including cytomegalovirus reactivation, hepatitis B virus infection and pneumonia. Conclusions: The combination of alemtuzumab plus DHAP might be an effective salvage chemotherapy regimen for PTCL-U patients. However, careful monitoring and dosage modification are warranted to prevent treatment-related toxicity.

Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma A clinicopathological study of nine cases

Apmis ◽  
2001 ◽  
Vol 109 (6) ◽  
pp. 419-427 ◽  
Author(s):  
Masaru Kojima ◽  
Shigeo Nakamura ◽  
Hideaki Itoh ◽  
Katsue Yoshida ◽  
Taizan Suchi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Low Grade ◽  
Peripheral T Cell Lymphoma ◽  
Clinicopathological Study

scholarly journals Efficacy and safety of geptanolimab (GB226) for relapsed or refractory peripheral T cell lymphoma: an open-label phase 2 study (Gxplore-002)

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuankai Shi ◽  
Jianqiu Wu ◽  
Zhen Wang ◽  
Liling Zhang ◽  
Zhao Wang ◽  
...  
Keyword(s):  
T Cell ◽  
Adverse Events ◽  
Cell Lymphoma ◽  
Objective Response ◽  
T Cell Lymphoma ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Peripheral T Cell Lymphoma ◽  
Serious Adverse Events ◽  
Phase 2 Study

Abstract Background Peripheral T cell lymphoma (PTCL) is a rare disease and recent approved drugs for relapsed/refractory (r/r) PTCL provided limited clinical benefit. We conducted this study to evaluate the efficacy and safety of geptanolimab (GB226), an anti-PD-1 antibody, in r/r PTCL patients. Methods We did this single-arm, multicenter phase 2 study across 41 sites in China. Eligible patients with r/r PTCL received geptanolimab 3 mg/kg intravenously every 2 weeks until disease progression or intolerable toxicity. All patients who received at least one dose of geptanolimab and histological confirmed PTCL entered full analysis set (FAS). The primary endpoint was objective response rate (ORR) in FAS assessed by the independent radiological review committee (IRRC) per Lugano 2014 criteria. Results Between July 12, 2018, and August 15, 2019, 102 patients were enrolled and received at least one dose of geptanolimab. At the data cutoff date (August 15, 2020), the median follow-up was 4.06 (range 0.30–22.9) months. For 89 patients in FAS, 36 achieved objective response (40.4%, 95% CI 30.2–51.4), of which 13 (14.6%) were complete response and 23 (25.8%) had partial response assessed by IRRC. The median duration of response (DOR) was 11.4 (95% CI 4.8 to not reached) months per IRRC. Patients with PD-L1 expression ≥ 50% derived more benefit from geptanolimab treatment compared to < 50% ones (ORR, 53.3% vs. 25.0%, p = 0.013; median PFS 6.2 vs. 1.5 months, p = 0.002). Grade ≥ 3 treatment-related adverse events occurred in 26 (25.5%) patients, and the most commonly observed were lymphocyte count decreased (n = 4) and platelet count decreased (n = 3). Serious adverse events were observed in 45 (44.1%) patients and 19 (18.6%) were treatment related. Conclusions In this study, geptanolimab showed promising activity and manageable safety profile in patients with r/r PTCL. Anti-PD-1 antibody could be a new treatment approach for this patient population. Trial registration: This clinical trial was registered at the ClinicalTrials.gov (NCT03502629) on April 18, 2018.

Safety and Efficacy of Mitoxantrone Hydrochloride Liposome in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma and Extranodal NK/T-Cell Lymphoma: A Prospective, Single-Arm, Open-Label, Multi-Center, Phase Ⅱ Clinical Trial

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 36-37
Author(s):  
Yan Gao ◽  
Huiqiang Huang ◽  
Xiaoxiao Wang ◽  
Bing Bai ◽  
Yunhong Huang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
T Cell ◽  
Adverse Events ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Objective Response ◽  
T Cell Lymphoma ◽  
Open Label ◽  
Peripheral T Cell Lymphoma ◽  
Pharmaceutical Technology

Background: Peripheral T cell lymphoma (PTCL) and Extranodal NK/T cell lymphoma (ENKTCL) are rare types of non-Hodgkin's lymphoma (NHL), with a higher incidence in Asian countries. Outcomes for patients with relapsed or refractory (R/R) PTCL and ENKTCL are very poor. There is still a lack of effective treatment for these patients. Mitoxantrone is a synthetic anthracenedione anti-cancer drug that is effective in lymphoma, leukemia, and other solid tumors. Liposome preparations have shown higher anti-tumor effect and lower toxicities due to modified drug release and particle shape. Mitoxantrone hydrochloride liposome (PLM60) was manufactured by Shijiazhuang Pharmaceutical Group Co., Ltd. (CSPC). High accumulation in tumor tissue was a key characteristic of PLM60 in our preclinical investigation. The pharmacokinetic parameters, especially half-life of PLM60 was prolonged significantly in phase Ⅰ trial. Phase II exploratory clinical trial showed promising results in R/R PTCL. Therefore, we conducted this pivotal registration phase II trial to evaluate the efficacy and safety of PLM60 in patients with R/R PTCL and ENKTCL. At the present time, this was the first clinical trial to assess PLM60 in treating R/R PTCL and ENKTCL worldwide. Methods : This was a prospective, single-arm, open-label, multi-center, phase II clinical trial. Adult patients with histologically confirmed PTCL (mainly peripheral T cell lymphoma, NOS, PTCL-NOS; angioimmunoblastic T-cell lymphoma, AITL; anaplastic large cell lymphoma, ALCL) after prior anthracyclines-based chemotherapy or ENKTCL failed from asparaginase-contained regimen, ECOG performance status ≤ 1, adequate organ function and bone marrow function, and at least one measurable or evaluable lesion were recruited in this trial. Main exclusion criteria were patients with a cumulative dose of doxorubicin &gt;360 mg/m2, known history of a clinically significant cardiac malfunction or uncontrollable cardiovascular diseases. PLM60 20mg/m2 was administered intravenously every 4 weeks. Treatment may continue for up to 6 cycles or until disease progression, or intolerable toxicity. The primary endpoint was objective response rate (ORR) based on Independent Review Committee (IRC) assessments according to Revised Response Criteria for Malignant Lymphoma (version 2007). Secondary endpoints included ORR based on assessment between investigators, duration of response (DoR), progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. Adverse events were rated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) 4.03. This trial is registered at ClinicalTrials.gov (NCT03776279). Results: One hundred and eight eligible patients were treated in 26 institutions in China between April 26, 2018 and May 19, 2020. Patient characteristics are summarized in Table 1. 98 patients were evaluable for response. 44 patients (40.7%, 95% CI, 31.4-50.6%) achieved an objective response including 22 (20.4%) patients achieved CR based on IRC assessment (Figure 1a). ORR were 34.4% (11/32), 50.0% (13/26), 52.4% (11/21), 12.5% (2/16) , 53.8% (7/13) and the CR rates were 18.8% (6/32), 23.1% (6/26), 28.6% (6/21), 6.3% (1/16), 23.1% (3/13) for PTCL-NOS, AITL, NKTCL, ALCL ALK+/-, and other subtypes , respectively (Figure 2). The ORR for patients who received at least 2 cycles of treatment (N=90) was 60.0% (95% CI, 49.1-70.2%). The investigator-evaluated ORR for the whole cohort was 43.5% (95% CI, 34.0-53.4%) (Figure 1b). Median DCR of all patients was 77.8% (95% CI, 68.8-85.2%). The median DoR of the whole group was 9.8 (95% CI, 5.1-not evaluated) months. 77.3% (34/44) of patients achieved response had a DoR ≥3 months (Figure 3). Median PFS of the whole cohort was 6.7 (95% CI, 5.5-10.4) months, with a 6-month PFS rate of 55.3% (95% CI, 44.5-64.8%). Median OS of the whole group was 16.3 (95% CI, 10.7-not evaluated) months, with a 6-month OS rate of 74.9% (95% CI, 64.9-82.4%) (Figure 4a, 4b). All-grade treatment-emergent adverse events (TEAEs, &gt;5%) are listed in Table 2. The most common toxicities of PLM60 were hematological toxicities. The most common grade ≥3 toxicities were leukocytopenia (50.0%) and neutropenia (45.4%). Conclusion: PLM60 monotherapy yielded promising results for patients with R/R PTCL and ENKTCL with moderate toxicities. Further investigation of combination therapy is warranted. Disclosures Xia: CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.: Current Employment. Xue:CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.: Current Employment. Li:CSPC ZhongQi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.: Current Employment.

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