Phase II Study of Epigenetic Therapy with Hydralazine and Valproate in Cutaneous T-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5362-5362 ◽  
Author(s):  
Ramiro Espinoza ◽  
Manuel Aguilar Rodríguez ◽  
Nidia P. Zapata ◽  
Jorge Carlos Torres ◽  
Diana Berenice Nolasco ◽  
...  
Keyword(s):  
T Cell ◽  
Partial Response ◽  
Phase Ii ◽  
Therapeutic Response ◽  
Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Epigenetic Therapy ◽  
Average Weight ◽  
Cutaneous T Cell Lymphoma

Abstract Objectives: To evaluate the therapeutic response to treatment with transcriptional therapy that combines hydralazine / valproate(Transkrip) in cancer patients with cutaneous T-cell lymphoma Determine toxicity, duration of response and time to progression of epigenetic therapy with hydralazine / valproate in patients with T-cell lymphomas Material and methods an open-label, phase II, prospective and longitudinal in the National Cancer Institute of Mexico was carried out, recruiting patients diagnosed with Cutaneous T based on WHO classification 2008, newly diagnosed untreated, demographic data were analyzed and vital and somatometry signs, assessment of efficacy was established according to the therapeutic response in lymphomas measured at each visit at the affected sites for each patient, using the m-SWAT system sorted in complete response (CR), partial response (PR ), stable disease (SD) and progression (PE) and is considered response to patients with complete or partial response, these data were collected in the form of case report at baseline in the first consultation, during treatment and at the end the study at each visit to the doctor. Statistical analysis was performed with SPSS version 13.0 software. results 16 patients were selected with diagnosis of cutaneous T-cell lymphoma, one patients discontinued the study at baseline and 4 patients had disease progression during the first months of the study, a total of 10 patients who completed 18 months of study continuing the compassionate use treatment. The median age of patients was 45.8 years analyzed (18-83 years) of which 8 are women (53%) and 7 men (47%) with an ECOG 1 in 93.3% of patients, with an average weight of 72.5 ± 15.99 kg, height 1.6 ± 0.1 m, body mass index 28.3 ± 5.7 kg / m2, 46.7% of overweight patients, systolic blood pressure an average of 116.2 ± 14.3 mmHg and diastolic 75.1 ± 11.04 mmHg with respiratory rate 19.43 ± 1.74 resp / min and 77.8 ± 12.3 cardiac beats / min. Of the 10 patients who completed the study, 100% had complete or partial response itching to 6 month continuing unchanged at month 18, the dream as an adverse event occurred in 33% of patients, this being more frequent, adverse events attributed to the drug were known, expected and mild. From 6 months of treatment, the percentage of partial response and complete response of m-SWAT and pruritus were greater than 90% of patients. conclusions: Hydralazine/Valproate (Transkrip) is a medication that offers patients with cutaneous T-cell lymphoma, both first-line and refractory, a therapeutic alternative with high efficiency and good safety profile. 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.

Tazarotene 0.1% Cream as Monotherapy for Early-Stage Cutaneous T-Cell Lymphoma

2016 ◽  
Vol 20 (3) ◽  
pp. 244-248 ◽  
Author(s):  
Catherine Besner Morin ◽  
David Roberge ◽  
Irina Turchin ◽  
Tina Petrogiannis-Haliotis ◽  
Gizelle Popradi ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Early Stage ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Open Label ◽  
Topical Retinoids ◽  
Few Data ◽  
Mean Time

Background: Numerous treatments are available for cutaneous T-cell lymphoma (CTCL), including systemic retinoids. Very few data are available on topical retinoids. Objectives: The aim of this study was to evaluate the safety and efficiency of tazarotene as monotherapy for early-stage CTCL. Methods: An open-label, prospective study of tazarotene as monotherapy for stages IA to IIA CTCL was conducted. Index lesions on 10 patients were followed for 6 months on treatment, plus at least 6 months off treatment. Results: Six patients (60%) showed complete response (CR). Erythema, scaling, thickness, and lesion area decreased progressively throughout treatment. The mean time to CR was 3.8 months; CR was durable for at least 6 months in 83%. Of the 4 patients (40%) without CR, 2 (20%) had stable disease and 2 (20%) stopped the medication because of local side effects; none showed progression. Conclusions: This is the first Canadian trial providing evidence that topical tazarotene has excellent potential as a monotherapy agent for stages I to IIA CTCL.

Multicenter Phase II Study of Mogamulizumab (KW-0761), a Defucosylated Anti-CCR4 Antibody, in Patients with Relapsed Peripheral and Cutaneous T-Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 795-795 ◽  
Author(s):  
Takashi Ishida ◽  
Michinori Ogura ◽  
Kiyohiko Hatake ◽  
Masafumi Taniwaki ◽  
Kiyoshi Ando ◽  
...  
Keyword(s):  
T Cell ◽  
Phase I ◽  
Clin Oncol ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Cell Subset ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Multicenter Phase

Abstract Abstract 795 Background: Mogamulizumab (KW-0761) is a humanized anti-CCR4 antibody engineered to exert potent ADCC by defucosylation. In a phase I study for patients with CCR4-positive T-cell malignancies, once weekly administration for 4 weeks of mogamulizumab was well tolerated up to 1.0 mg/kg, and encouraging efficacy was observed (J Clin Oncol 2010;28:1591). In a subsequent phase II study in CCR4-positive relapsed adult T-cell leukemia-lymphoma (ATL) patients, mogamulizumab exhibited an overall response rate (ORR) of 50% (J Clin Oncol 2012;30:837), leading to its approval in Japan in 2012 for relapsed/refractory ATL. In addition, a phase I/IIa study for previously treated cutaneous T-cell lymphoma (CTCL) in the USA showed an ORR of 37% (14/38) (T-CELL LYMPHOMA FORUM 2012). Based on these findings, a phase II study of mogamulizumab for relapsed peripheral T-cell lymphoma (PTCL) and CTCL was conducted in Japan. Methods: A multicenter phase II study of mogamulizumab monotherapy for patients with relapsed CCR4-positive PTCL and CTCL was conducted to evaluate efficacy, pharmacokinetic profile, and safety. The primary endpoint was ORR and secondary endpoints included progression-free survival (PFS) and overall survival (OS). At least 35 patients were needed to detect a lower limit of the 95% confidence interval (CI) exceeding the 5% threshold, with an expected ORR for mogamulizumab of 25% with 90% statistical power. Patients received intravenous infusions of mogamulizumab once per week for 8 weeks at a dose of 1.0 mg/kg. Responses were assessed after the 4th and 8th infusions of mogamulizumab by an independent efficacy assessment committee. The histopathological subtypes of PTCL were confirmed by an independent pathology review committee according to the 2008 WHO classification. In addition, we examined blood T-cell subset distributions. Results: A total of 38 patients were enrolled, and 37 patients (male/female 23/14; median age 64 years, range 33–80) received mogamulizumab. One patient was withdrawn due to an infectious complication. Twenty-nine of the 37 assessable patients had PTCL [PTCL- not otherwise specified (NOS), n=16; angioimmunoblastic T-cell lymphoma (AITL), n=12; anaplastic large cell lymphoma (ALCL)-ALK negative, n=1] and 8 had CTCL [mycosis fungoides (MF), n=7; cutaneous ALCL, n=1]. Performance status at enrollment was 0 (n=24), 1 (n=12), and 2 (n=1). The median number of prior systemic chemotherapy regimens was 2 (range 1–6). Of the 37 patients, 25 completed the schedule of 8 planned infusions. Nine patients (24%) discontinued the treatment protocol due to progressive disease and 3 due to adverse events (AEs). The ORR in 37 patients was 35% (13/37, 95% CI, 20 to 53%) with 14% having a complete response (5/37) (Table 1). By PTCL subtype, the ORR was 34% (10/29) for PTCL (3/16 for PTCL-NOS, 6/12 for AITL, and 1/1 for ALCL-ALK negative) and 38% (3/8) for CTCL (2/7 for MF and 1/1 for cutaneous ALCL). AEs possibly, probably, or definitely related to mogamulizumab monotherapy were as follows. Lymphopenia of all grades and that of grades 3–4 were observed in 78% and 70% of the 37 patients, respectively. Leukopenia of all grades and that of grades 3–4 were observed in 43% and 14% of the 37 patients. For all grades and grades 3–4, neutropenia was observed in 35% and 16%, thrombocytopenia in 35% and 3%, ALT increases in 22% and 3%, and skin eruptions in 49% and 8% of patients, respectively. Infusion-related toxicities occurred in 22%, which were all within grade 2 or lower. Fourteen severe AEs were observed in 7 patients, including a grade 3 polymyositis in 1 and grade 2 cytomegalovirus retinitis in 2. All severe AEs were improved. No grade 5 AEs were observed. Pharmacokinetic analysis demonstrated that Cmax and trough (C168h) after the 8th infusion were 45.9 ± 9.3 and 29.0 ± 13.3 μg/mL, respectively. No anti-mogamulizumab antibody has been detected. Updated results of PFS, OS, and T-cell subset analysis are being analyzed for presentation. Conclusions: Mogamulizumab monotherapy showed promising antitumor activity with acceptable toxicity profiles in patients with relapsed PTCL and CTCL, warranting further investigation. Disclosures: Ishida: Kyowa Hakko Kirin Co., Ltd,: Honoraria, Research Funding, Speakers Bureau. Ogura:Kyowa Hakko Kirin Co., Ltd,: Consultancy. Suzumiya:Kyowa Hakko Kirin Co., Ltd,: Consultancy. Inagaki:Kyowa Hakko Kirin Co., Ltd,: Consultancy. Tamura:Kyowa Hakko Kirin Co., Ltd,: Consultancy. Akinaga:Kyowa Hakko Kirin Co., Ltd,: Employment. Tomonaga:Kyowa Hakko Kirin Co., Ltd,: Consultancy. Ueda:Kyowa Hakko Kirin Co., Ltd,: endowed chair Other.

Phase II study of oral panobinostat (LBH589), a potent pan-deacetylase inhibitor, in patients with refractory Cutaneous T-cell Lymphoma (CTCL)

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 8555-8555 ◽  
Author(s):  
M. Duvic ◽  
F. Vanaclocha ◽  
M. G. Bernengo ◽  
C. Okada ◽  
D. Breneman ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Deacetylase Inhibitor

A multicenter, open label, phase II study to assess the efficacy and safety of APO866 in the treatment of patients with refractory or relapsed cutaneous T-cell lymphoma.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e20044-e20044
Author(s):  
Simone M. Goldinger ◽  
Sharon Gobbi ◽  
Michelle Ding ◽  
Anna Lisa Frauchiger ◽  
Regina Fink-Puches ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Efficacy And Safety ◽  
Open Label ◽  
Open Label Phase

Phase II Trial of Oral Panobinostat (LBH589) in Patients with Refractory Cutaneous T-Cell Lymphoma (CTCL).

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1005-1005 ◽  
Author(s):  
Madeleine Duvic ◽  
Jürgen C. Becker ◽  
Stephane Dalle ◽  
Francisco Vanaclocha ◽  
Maria Grazia Bernengo ◽  
...  
Keyword(s):  
T Cell ◽  
Ct Scan ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Systemic Disease ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Efficacy And Safety ◽  
Deacetylase Inhibitor ◽  
Skin Responses

Abstract Background: Panobinostat is a histone deacetylase inhibitor that has shown promising results in cutaneous T-cell lymphoma (CTCL). Objectives: An open-label, multicenter, Phase II study is being conducted with a primary objective of establishing the efficacy and safety of the pan-deacetylase inhibitor, panobinostat (LBH589), for patients (pts) with relapsed/refractory CTCL with Stage IB–IVA mycosis fungoides (MF) or Sézary syndrome (SS). Methods: Inclusion criteria include adequate organ function, no clinically significant cardiovascular abnormalities (QTcF ≤ 450 ms, ECOG PS ≤2), failure of ≥2 prior systemic therapies, and no prior HDAC inhibitor treatment. Pts were grouped as having bexarotene therapy (Group [Gr] 1) or bexarotene naïve (Gr 2). Panobinostat was administered at a dose of 20 mg orally on Days 1, 3, 5, weekly, every 28 days until progression or unacceptable toxicity. Response was based on a composite score, including skin assessment with the modified Severity-Weighted Assessment Tool (mSWAT) and systemic disease assessed by CT scan. Results: To date, 95 pts (Gr 1=62; Gr 2=33) have enrolled with median age of 58 yrs [range 25–88]: 58 male, 37 female; 70 MF, 25 SS. Median prior treatment regimens are 4 and 3 for Gr 1 and 2, respectively. Most pts were ≥Stage IIB at study entry (Gr 1=42; Gr 2=26) and received 1–17+ (median=3) treatment cycles of panobinostat. In Gr 1, 11/62 pts have had confirmed skin responses by SWAT, including 2 complete skin responses. Confirmatory CT scans are pending for 2 patients. In Gr 2, 4/33 pts had confirmed skin and CT scan responses. Common AEs (>20%; all grades, regardless of causality) included diarrhea, thrombocytopenia, nausea, pruritus, fatigue, and asthenia, and Grade 3/4 AEs (>2%, regardless of causality) included thrombocytopenia, neutropenia, pruritus, diarrhea, and hypophosphatemia. Of 4,542 ECGs analyzed, 2 pts have had QTcF >480 ms; 4 had QTcF >60 ms increase from baseline. Conclusions: Panobinostat continues to demonstrate encouraging clinical activity with a manageable safety profile in pts with CTCL. Per predefined criteria, Group 2 enrollment to Stage 2 is open. Updated efficacy and safety data will be presented.

Phase II Study of Chidamide, a New Subtype-Selective Oral Histone Deacetylase Inhibitor, in Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1513-1513 ◽  
Author(s):  
Yuankai Shi ◽  
Mei Dong ◽  
Jun Zhu ◽  
Daobin Zhou ◽  
Huiqiang Huang ◽  
...  
Keyword(s):  
T Cell ◽  
Histone Deacetylase ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Objective Response ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Dosing Regimens ◽  
Subtype Selective

Abstract Background Chidamide (CS055) is a new oral benzamide type of histone deacetylase (HDAC) inhibitor with subtype selective activity against HDAC1, 2, 3 and 10, and it has been approved for relapsed or refractory peripheral T-cell lymphoma (PTCL) in China. This phase II study (ChiCTR-TNC-00000806) was to evaluate the efficacy and safety of chidamide in different dosing regimens in patients with relapsed or refractory cutaneous T-cell Lymphoma (CTCL). Methods Fifty-two patients, all were mycosis fungoides or Sezary syndrome, were enrolled in this study. In the first stage of the study, 26 patients were randomly assigned to receive chidamide 30 mg twice per week for 2 weeks out of a 3-week-cycle (13 patients), or 4 weeks out of a 6-week-cycle (13 patients). Another 26 patients were enrolled in the second stage, and were treated by chidamide of 30 mg twice per week without drug-free holiday. The primary endpoint was objective response rate (ORR). Responses were evaluated based on the overall skin lesions, lymph nodes, blood cells and pruritis. Results The ORRs were 33% (4/12 PRs) for the 3-week-cycle arm, 23% (3/13 PRs) for the 6-week-cycle arm, and 36% (1/25 CR + 8/25 PRs) for the successive dosing arm, respectively. Median duration of response (DOR) was 50, 92, and 169 days for the indicated 3 arms, respectively. Twelve (92%), 11 (85%) and 20 (77%) patients experienced adverse event (AE) in the three arms. Most AEs were in Grade 1 or 2. Thrombocytopenia, leucopenia, fatigue, nausea and diarrhea were most frequently seen. Two serious adverse events (SAE) were reported in the study. One patient in the 3-week-cycle arm was hospitalized for fever and lung infection, and the other in the successive dosing arm was hospitalized for hyperglycemia. Conclusions Chidamide was active and tolerable to relapsed or refractory CTCL. The ORR of chidamide was comparable with the marketed drugs for CTCL. The major toxicities of chidamide were hematologic and gastrointestinal reactions which were controllable. Based on the overall profiles of the three different dosing regimens, 30 mg twice per week successively was clinically recommended. Table 1. Efficacy 3-week-cycle arm(N=12) * 6-week-cycle arm (N=13) Successive dosing arm(N=25) * CR 0 0 1 PR 4 3 8 ORR (%) 4 (33) 3 (23) 9 (36) Median DOR (days) 50 92 169 Median PFS (days) 84 81 88 *patients with ineligible entrance of the study were excluded for the efficacy analysis Table 2. Safety 3-week-cycle arm (N=13) 6-week-cycle arm (N=13) Successive dosing arm (N=26) Patients with AE (%) 12 (92) 11(85) 20 (77) Patients with AE ≥grade 3 (%) 3 (23) 5 (38) 4 (15) Patients with SAE (%) 1 (8) 0 1 (4) AEs in ≥10% of patients (%) Thrombocytopenia 5 (39) 3 (23) 9 (35) Leucopenia 7 (54) 4 (31) 4 (15) Fatigue 3 (23) 3 (23) 3 (12) Nausea 3 (23) 1 (8) 3 (12) Diarrhea 1(8) 1 (8) 3 (12) Fever 0 2 (15) 2 (8) Anemia 1 (8) 2 (15) 1 (4) Disclosures No relevant conflicts of interest to declare.

Results of a phase II study of 506U78 in cutaneous T-cell lymphoma and peripheral T-cell lymphoma: CALGB 59901

2007 ◽  
Vol 48 (1) ◽  
pp. 97-103 ◽  
Author(s):  
Myron S. Czuczman ◽  
Pierluigi Porcu ◽  
Jeffrey Johnson ◽  
Donna Niedzwiecki ◽  
Michael Kelly ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma
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