CALGB 59901: Results of a Phase II Study of 506U78 in CTCL and PTCL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2486-2486 ◽  
Author(s):  
Myron S. Czuczman ◽  
Pierluigi Porcu ◽  
Jeff Johnson ◽  
Donna Niedzwiecki ◽  
George P. Canellos ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Western Hemisphere ◽  
Water Soluble ◽  
T Cell Lymphoma ◽  
Grade 3

Abstract T-cell lymphoma comprises approximately 10% to 15% of all lymphomas seen in the Western hemisphere and may be broadly categorized into 2 main groups: the various histologies of peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Overall, PTCL patients (pts) are believed to have a worse prognosis than pts with B-cell lymphoma. Except for the favorable subset of ALK-1-positive anaplastic large cell lymphoma, most PTCL are incurable with standard therapy. Salvage chemotherapy is often ineffective in relapsed PTCL or in pts with advanced CTCL no longer responding to agents that modulate T-cell function (e.g. retinoids, interferons, antibodies). New agents are needed for these pts. 506U78 is a pro-drug of ara-G, a deoxyguanosine analogue. Ara-G itself is difficult to synthesize and poorly water soluble. 506U78 is 10 X more water soluble than ara-G and is rapidly demethoxylated in blood to ara-G, which has been shown to be toxic to T-cells at even micromolar concentrations. Based on positive preliminary data with 506U78 in pediatric pts with recurrent/refractory precursor T-lymphoblastic lymphoma or leukemia (PTLL), we activated CALGB protocol 59901, a Phase II study of 506U78 in pts with systemically untreated CTCL or refractory/relapsed PTCL. Objectives were to determine response rate, remission duration, and safety associated with 506U78 given at 1.5 g/m2/day on Days 1, 3, and 5 as an IV infusion q 21 days for a minimum of 2 cycles and/or to continue for 2 cycles after CR (up to max of 8 cycles). Eligibility included: diagnosis of PTCL or CTCL; measurable disease; no CNS lymphoma; no history of seizure disorder or significant (>grade 1) neurologic dysfunction; age <70; PS 0–2; adequate renal and hepatic function; CTCL pts were originally not permitted to have received systemic chemo, but the protocol was amended on 2/15/02 to allow therapy with one prior course of single-agent chemotherapy in an attempt to increase accrual. Nineteen pts were enrolled between 5-15-00 and 3-15-04: 11 CTCL and 8 PTCL pts. Five of 11 CTCL pts had received no prior therapy and 7 of 7 evaluable PTCL pts had received prior chemo and 2 prior BMT. Adverse event (AE) data are available for 18 pts. Grade 3 or 4 AEs were documented in 50% and 28% of pts, respectively. Thirty-three percent of pts experienced Grade 3 or 4 neurologic toxicities which included: ataxia, vertigo, peripheral neuropathy, confusion, and/or depressed consciousness. There were 2 treatment-related deaths, 1 due to infection and 1 due to CNS hemorrhage (both in pts with CTCL). There were 2 PRs to therapy, one each in the PTCL and CTCL groups, with disease progression at 3m and 5.5m, respectively. The overall response rate is 10.5% (1.3% – 33.1%; 95% CI). Fifteen of 19 pts have died. Median EFS was 1.2m (1.0, 1.6 m; 95% CI) and median OS was 3 months (1.4, 9.8m; 95% CI). Due to lack of efficacy and excessive toxicity the protocol was closed on 3/15/04. In contrast to the favorable results seen in pediatric pts with recurrent PTLL, our data demonstrate that 506U78 has low efficacy, is unacceptably toxic and is not recommended as monotherapy in adult pts with CTCL and PTCL.

Pegylated liposomal doxorubicin (PLD) as an alternative treatment of cutaneous T-cell lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8096-8096
Author(s):  
G. Quereux ◽  
A. Khammari ◽  
J. M. Nguyen ◽  
M. Benmiloud ◽  
B. Dreno
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Treatment Duration ◽  
Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Palmoplantar Erythrodysesthesia ◽  
Grade 3

8096 Background: Therapy of cutaneous T-cell lymphoma (CTCL) at early stages consists of various modalities. The advanced or transformed stage of CTCL is treated by the CHOP regimen as standard chemotherapy; has a 40% response rate and relapses within 6 months in > 60% of pts. Methods: A prospective open multicentre Phase II study to evaluate the use of PLD as a CTCL therapeutic agent, with 25 pts, (59±12 years). Eligibility criteria: Pts with histologic proof of CTCL stage II to IV, unresponsive to at least 2 lines of therapy; transformed CTCL or non epidermotropic lymphoma CD30 + or CD30. PLD was administered i.v., 40 mg/m2 every 4 wks for 8 cycles. Objective of study was overall response rate (ORR); secondary objectives were safety, disease-free survival (DFS) and overall survival (OS). Results: Phase II study of 14pts with CTCL stage IIb/III, and 11pts with transformed CTCL, at baseline. Treatment duration was 8 cycles in 13 pts, 2–6 cycles in 10pts, and 2 pts were withdrawn during cycle 1 due to anaphylactic-like reactions. Among 23 treated pts, 5pts (22%) achieved a complete response (CR), 9pts (39%) a partial response (PR), with 61% ORR. DFS was 18 ± 4.5 mos; longest treatment duration was 24 mos. Median OS was 28 ± 3 mos. In general, PLD treatment was well tolerated. The main adverse events were grade 3 neutropenia (4%); grade 3 septicemia (8%) and 1 case of bilateral grade 3 pneumopathy. There were only 3 cases of grade 1 palmoplantar erythrodysesthesia. Conclusions: This is the first prospective multicentric study investigating activity and tolerance of 40 mg/m2 q28days of PLD in CTCL. The current study confirmed effectiveness of PLD(∼61%) in CTCL treatment, but did not show improved efficacy with dose increases (Wollina, Cancer, 2003). This data combined with Wollina’s data, support the use of PLD as a promising therapy in advanced stages of CTCL. The duration of response is superior to that achieved with CHOP. This has been confirmed in a small, trial, and needs to be confirmed in a larger trial. No significant financial relationships to disclose.

Results of a Phase II Study of 506U78 (Nelarabine) in Refractory Indolent B-Cell or Peripheral T-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2681-2681 ◽  
Author(s):  
Michael A. Thompson ◽  
Barbara Pro ◽  
Andreas Sarris ◽  
Fredrick B. Hagemeister ◽  
Andre Goy ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Single Agent ◽  
Complete Response ◽  
Water Soluble ◽  
Adult T Cell Leukemia ◽  
Grade 3

Abstract BACKGROUND: Compound 506U78 (Nelarabine), a water soluble pro-drug of 9-β-d-arabinofuranosyl-guanine, is demethoxylated by adenosine deaminase to ara-G in lymphoblasts. Intracellular ara-G is then phosphorylated via deoxycytidine kinase and mitochondrial deoxyguanosine kinase to its active 5′-triphosphate, ara-GTP. Ara-GTP, a potent inhibitor of DNA polymerase, also incorporates into DNA resulting in cell death. Studies in children and adult T-cell leukemia and non-Hodgkin’s lymphoma (NHL) have shown activity, but with reversible neurotoxicity as the most prominent adverse event. METHODS: We report here the results of a phase II study with 506U78 in adults (median age 64, range 33–81) with relapsed or refractory indolent B-cell or peripheral T-cell NHL. Patients had received a median of 2 prior courses of chemotherapy. 506U78 was given at 1.5 g/m2/day IV on days 1, 3, and 5 every 28 days to a maximum of 6 cycles unless toxicity or progressive disease. If after 4 cycles a complete response (CR) or partial response (PR) was not achieved, then treatment was discontinued. RESULTS: There were 23 patients enrolled including 13 with T-cell and 10 with indolent B-cell NHL. Among 19 assessable for response, the overall response rate (ORR) in T-cell NHL was 4/9 (44%) with 2 CR and 2 PR, while in indolent B-cell NHL the PR was 3/9 (33%) with no CR. In responders, the median time to progression (TTP) was 8 months (range 2–22 months). Sixteen of 22 (73%) patients evaluable for toxicity had grade 3 or 4 adverse events. Neurotoxicity included one grade 3 and one grade 4 event. CONCLUSION: Compound 506U78 is active as a single agent in T-cell and B-cell NHL. Our response rate was higher than the ORR of 10.5% reported previously in the Czuczman et al. (2004) Blood 104(11) abstract in adults with T-cell NHL and there was less neurotoxicity in our study. This may be related to different dosing regimens (every 28 days vs. every 21 days). Compound 506U78 should be further evaluated in clinical trials.

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 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.

A Phase II Study of the Farnesyltransferase Inhibitor Tipifarnib Demonstrates Anti-Tumor Activity In Patients with Relapsed and Refractory Lymphomas

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 287-287
Author(s):  
Thomas E. Witzig ◽  
Tang Hui ◽  
Ivana N Micallef ◽  
Stephen M. Ansell ◽  
Brian Link ◽  
...  
Keyword(s):  
T Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response Duration ◽  
T Cell Lymphoma ◽  
Farnesyltransferase Inhibitor ◽  
Median Response

Abstract Abstract 287 Purpose: Farnesyltransferases are key cellular enzymes involved in the prenylation of proteins. Prenylated proteins are important for malignant cell growth. The purpose of this phase II study (NCT00082888) was to assess tumor response and toxicity associated with the oral farnesyltransferase inhibitor tipifarnib (R115777, Johnson and Johnson) in patients with relapsed aggressive, indolent, or uncommon lymphoma. The uncommon group included low incidence lymphoma types such as Hodgkin lymphoma (HL) and T-cell non-Hodgkin lymphoma- cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). Patients and Methods: Patients with relapsed or refractory non-Hodgkin (NHL) or Hodgkin (HL) were eligible if they had measurable disease, performance status ≤2, platelet count ≥75,000 × 10(6)/L, an absolute neutrophil count ≥1000 × 10(6)/L and a creatinine ≤2 × upper limit of normal. Patients initially received tipifarnib 300 mg twice daily, days 1–21 every 28 days. The trial was conducted by the University of Iowa/Mayo Clinic Lymphoma SPORE. Results: Ninety-three patients with lymphoma (42 aggressive, 15 indolent, and 36 uncommon) enrolled in the trial between March 2004 and November 2008. The median age was 62 years (range, 18–91). The median number of prior therapies was 5 (range, 1–17). The overall response rate (ORR) was 20% (19/93) with 6% (6/93) complete responses (CR) and 14% (13/93) partial responses (PR). The ORR was 17%, 7%, and 31% for the aggressive, indolent, and uncommon groups, respectively (Table). Among the 19 responders were 7 diffuse large B-cell lymphoma (DLBCL), 7 T-cell NHL, 1 follicular grade II, and 4 HL. The overall median response duration for the 19 responders was 7.5 months (mean, 12.8; range, 1.8 – 48.1 months). The median response duration was 11.3 months (mean, 10.1; range, 1.8 – 18.5 months), 2 months, and 7.5 months (mean, 15.5; range, 1.9 – 48.1 months) for the aggressive (7), indolent (1), and uncommon (11) groups, respectively. Five patients in the uncommon group are still receiving treatment with a range of treatment duration between 25 – 60+ months. Among the 5 still receiving treatment 4 responded and 1 is stable. The range of response duration is 15.4, 17.7, 43.1, and 48.1 months. These five patients (2 with HL, 1 anaplastic large cell cutaneous, and 2 PTCL) are currently receiving doses of 400 (1), 200 (2), and 100 (2) mg twice daily. The median time to progression for all patients was 3.6 months (95% CI: 2.1 – 4.5 months). The grade 3,4 toxicities observed were primarily fatigue (10%) and reversible myelosuppression with 11% anemia, 37% neutropenia, and 32% thrombocytopenia. Correlative studies demonstrated tipifarnib-induced upregulation of Bim, a marker of tipifarnib action in lymphoma cell lines, in 7 of 9 paired lymphoma biopsies. Conclusions: Tipifarnib has activity in lymphoma, with responses in patients with heavily pretreated DLBCL, HL and T-cell types, but little activity in follicular NHL. This agent has an excellent toxicity profile and targets a novel pathway. Further studies in combination with other agents are warranted for patients with DLBCL, HL or T-cell NHL. Disclosures: No relevant conflicts of interest to declare.

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.

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