CHOP/CHOEP-14 followed by consolidation with alemtuzumab in untreated aggressive T-cell lymphomas (DSHNHL 2003–1): Feasibility and toxicity of a phase II trial of the German High Grade Non-Hodgkin’s Lymphoma Group DSHNHL

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7538-7538 ◽  
Author(s):  
L. H. Trumper ◽  
K. Hohloch ◽  
M. Kloess ◽  
U. Dührsen ◽  
H. Eimermacher ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Trial ◽  
Remission Rate ◽  
Large Cell ◽  
Phase Iii ◽  
Tumor Control ◽  
Treatment Protocols ◽  
T Cell Lymphomas

7538 Background: The clinical course of peripheral T-cell lymphomas (PTCL) is unfavourable. Treatment protocols developed for aggressive B-NHL are employed, with significantly worse outcomes. The MoAb alemtuzumab (CAM) has shown promising activity in T-NHL, although its use may be complicated by severe infections. Methods: In 2003, the DSHNHL group initiated a prospective multicenter phase II trial for previously untreated PTCL. Six cycles of either CHOEP-14 (< 60 y) or CHOP-14 (> 60 y) with G-CSF support are followed by a short consolidation course with CAM, when either a CR or a good PR has been achieved. Inclusion criteria: PTCL-NOS, AILD, intestinal T-NHL, anaplastic large cell T-NHL (ALK negative); age 18–70 y; all IPIs; ECOG PS 0–3. The primary endpoint is feasibility, measured by occurrence SAE and protocol adherence. Secondary endpoints are remission rate, TTF, OS, DFS, tumor control and TRM. CAM is given at a total dose of 133 mg over 4 weeks. Prophylaxis against PCP and herpes infections is mandatory during CAM therapy and is continued until CD 4 cells are > 200/μl. CMV-positive patients are monitored weekly. Results: 35 (of the planned 37) pts have been enrolled, 31 are evaluable. 5/31 pts are still undergoing chemotherapy. 7/31 pts had progressive disease or NC under/after chemotherapy and did not receive CAM. 18 of the 19 pts who achieved a CR/PR (15/4) received CAM. 12 of the CAM pts are in continuous CR, 7 had progressive disease or relapsed. There was no treatment-related death. Of 7 registered SAEs, 3 were related to chemotherapy, 4 to CAM (1 fungal pneumonia, 2 CMV pneumonias, 1 bacterial sepsis after dental procedure). Other CAM side effects were: Herpes Zoster (1), CMV-reactivation (1), grade III-IV neutropenias (2). All pts recovered with appropriate treatment. Conclusion: Preliminary analysis demonstrates that the combination of CHO/E/P-14 followed by a short course of CAM consolidation therapy is feasible without TRM. The adverse effects related to infections can be severe but manageable upon careful monitoring and close follow-up. The phase II trial will close in 4/2006, to be followed by a randomized phase III trial of A-CHOP-14 vs CHOP-14. No significant financial relationships to disclose.

Intensified Chemo-Immunotherapy Including up-Front Autologous or Allogeneic Stem Cell Transplantation (SCT) for Young Patients with Newly Diagnosed Peripheral T-Cell Lymphomas: Final Results of a Phase II Multicenter Prospective Clinical Trial

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1984-1984
Author(s):  
Paolo Corradini ◽  
Umberto Vitolo ◽  
Alessandro Rambaldi ◽  
Rosalba Miceli ◽  
Francesca Patriarca ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Phase Ii ◽  
Progressive Disease ◽  
Newly Diagnosed ◽  
Risk Of Death ◽  
T Cell Lymphomas ◽  
Short Course ◽  
Early Progressive Disease ◽  
Peripheral T Cell Lymphomas

Abstract Abstract 1984 Background: Peripheral T-cell lymphomas (PTCL) are characterized by a poor prognosis, conventional chemotherapy provides a long-term survival of approximately 25%. Few prospective data suggest that autologous SCT (autoSCT) can improve prognosis when used up-front. Allogeneic SCT (alloSCT) can obtain a durable disease control at relapse in 40% of patients (pts). Based upon these premises, we designed a phase II trial for young pts (age 18 –60 yrs) in which intensified chemo-immunotherapy was used before auto or alloSCT. Transplant type was decided according to the donor availability. Primary endpoint was CR rate at one year after the end of treatment. This was the first prospective trial employing high-dose (hd) chemo-immunotherapy and alloSCT frontline in PTCLs. Methods: 64 pts with newly diagnosed PTCL (ALK-positive ALCL cases were excluded) were included (EudraCT N° 200600423433). Histology was centrally reviewed. The intensified pre-transplant phase consisted of 2 courses of CHOP-21 regimen preceded by alemtuzumab (30 mg total dose) followed by 2 courses of Hyper-C-Hidam (hd-methotrexate, hyper-fractionated cyclophosphamide and hd-ara-C). Autologous stem cells were collected after the second Hyper-C-Hidam or after a short course of intermediate dose Ara-C. Responding pts were transplanted according to a genetic stratification based on donor availability: pts with HLA-identical, one antigen mismatched sibling, or allele matched unrelated donors (MUD) received alloSCT. Conditioning regimen was thiotepa-fludara-cyclophosphamide [Corradini et al JCO 2004]; GVHD prophylaxis was cyclosporine, short course methotrexate and 7 mg/kg of Thymoglobuline for alternative donors only. Pts without a donor received BEAM followed by autoSCT. Results: A total of 64 pts were enrolled, but 61 fulfilled all the inclusion criteria and were thus evaluable. Diagnosis included PTCL-not otherwise specified (PTCL-NOS, n=38), ALK-negative ALCL (n=12), angioimmunoblastic lymphoma (AILT, n=9), enteropathy-type T-cell lymphoma (n=2). Median age was 48 years (range, 24–60 yrs). Fifty-seven pts (93%) had advanced disease; IPI was <2: 19 pts (31%), and ≥2: 42 pts (69%); PIT was 0–1 risk factors in 40 (66%), 2–4 risk factors in 21 (34%). Of 61 pts, 56 completed alemtuzumab-CHOP whereas 5 pts had early progressive disease (PD). After induction phase, 38 pts (62%) achieved a response [n=31 CR (51%), n= 7 PR (11%)] whereas 18 (30%) had PD and 5 (8%) died of toxicity in the Hyper-C-Hidam phase. All the 18 pts with early PD died of disease at median time of 180 days since the beginning of treatment. Transplantation-eligible pts were 38 (62%): 14 underwent autoSCT and 23 alloSCT whereas one patient, in continuous CR, did not receive autoSCT for previous viral infection. Overall, at a median follow-up of 33 months, 30 pts (49%) are alive in CR and 31 died (51%) (n=8 death for toxicity, n=23 for PD). Eleven of 14 pts who received autoSCT are alive in CR (3 relapsed). Sixteen of 23 pts who received alloSCT (n=10 matched siblings; n=13 MUD) are alive in CR, 4 (17%) died of disease, and 3 died for toxicity. In a intention-to-treat analysis, the estimated 3-years disease-free survival (DFS), PFS and overall survival (OS) values for entire cohort (61 pts) were 76%, 44%, 47%, respectively. The 3-year cumulative incidence of non-relapse mortality (NRM) and relapse were 13% and 42%, respectively. In univariate analysis, involvement of liver and/or gastrointestinal tract was associated to a poor outcome [PFS: 21% versus 53% (p=0.03); OS: 27% versus 55% (p=0.07)]. At multivariable analysis by Cox model (including as variables IPI, extranodal disease, response and SCT), pts not achieving a clinical response and not receiving SCT had a 5.8 (p=0.0003)- and 8-fold (p=0.0002) risk of death as compared to pts responding and transplanted. Pts not in response or in partial response had a 20-fold (p< 0.0001)- and 3-fold (p=0.07) risk of progression as compared to pts with CR maintained for at least 6 months. Conclusions: Our findings indicate: 1) the achievement of CR is an independent predictor of longer PFS and OS, regardless of IPI or gastric/liver disease; 2) although the trial was not sized for a formal comparison, up-front autoSCT appeared not inferior to alloSCT in responding pts; 3) the use of alemtuzumab and pre-transplant hd-chemotherapy did not reduce the amount of primary refractory or early progressive disease although SCT improves survival. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Dose-adjusted EPOCH chemotherapy for untreated peripheral T-cell lymphomas: a multicenter phase II trial of West-JHOG PTCL0707

Haematologica ◽  
2017 ◽  
Vol 102 (12) ◽  
pp. 2097-2103 ◽  
Author(s):  
Yoshinobu Maeda ◽  
Hisakazu Nishimori ◽  
Isao Yoshida ◽  
Yasushi Hiramatsu ◽  
Masatoshi Uno ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Multicenter Phase ◽  
T Cell Lymphomas ◽  
Peripheral T Cell Lymphomas

scholarly journals Phase II Intergroup Trial of Alisertib in Relapsed and Refractory Peripheral T-Cell Lymphoma and Transformed Mycosis Fungoides: SWOG 1108

2015 ◽  
Vol 33 (21) ◽  
pp. 2399-2404 ◽  
Author(s):  
Paul M. Barr ◽  
Hongli Li ◽  
Catherine Spier ◽  
Daruka Mahadevan ◽  
Michael LeBlanc ◽  
...  
Keyword(s):  
T Cell ◽  
Mycosis Fungoides ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Phase Iii ◽  
Aurora B ◽  
Aurora A Kinase ◽  
Aurora B Kinase

Purpose Aurora A kinase (AAK) is upregulated in highly proliferative lymphomas, suggesting its potential as a therapeutic target. Alisertib is a novel oral AAK inhibitor without adverse safety signals in early-phase studies that demonstrated preliminary activity in T-cell lymphoma. This phase II study was conducted to further investigate the efficacy of alisertib in relapsed or refractory peripheral T-cell non-Hodgkin lymphoma (PTCL). Patients and Methods Eligible patients with histologically confirmed relapsed/refractory PTCL or transformed Mycosis fungoides (tMF) received alisertib 50 mg twice a day for 7 days on 21-day cycles. Results Of 37 eligible patients, the histologic subtypes enrolled included PTCL not otherwise specified (n = 13), angioimmunoblastic T-cell lymphoma (n = 9), tMF (n = 7), adult T-cell lymphoma/leukemia (n = 4), anaplastic large-cell lymphoma (n = 2), and extranodal natural killer/T-cell lymphoma (n = 2). Grade 3 and 4 adverse events in ≥ 5% of patients included neutropenia (32%), anemia (30%), thrombocytopenia (24%), febrile neutropenia (14%), mucositis (11%), and rash (5%). Treatment was discontinued most commonly for disease progression. Among the PTCL subtypes, the overall response rate was 30%, whereas no responses were observed in tMF. Aurora B kinase was more commonly overexpressed than AAK in tumor specimens. Analysis of AAK, Aurora B kinase, MYC, BCL-2, phosphatidylinositol 3-kinase γ, and Notch1 expression revealed no association with response. Conclusion Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL.

scholarly journals A PHASE II TRIAL OF REDUCED DOSE BRENTUXIMAB VEDOTIN FOR CUTANEOUS T‐CELL LYMPHOMAS

2021 ◽  
Vol 39 (S2) ◽  
Author(s):  
N. Khan ◽  
S. Noor ◽  
S. Geller ◽  
M. S. Khodadoust ◽  
M. Kheterpal ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Brentuximab Vedotin ◽  
Reduced Dose ◽  
T Cell Lymphomas

Efficacy and safety of bevacizumab combined with chemotherapy in the treatment of patients with metastatic well-differentiated duodeno-pancreatic endocrine tumors (BETTER study).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4036-4036 ◽  
Author(s):  
Michel Ducreux ◽  
Jean-François Seitz ◽  
Denis Smith ◽  
Dermot O'Toole ◽  
Céline Lepère ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Tumor Control ◽  
Endocrine Tumors ◽  
Efficacy And Safety ◽  
Ki 67 ◽  
Pancreatic Net ◽  
Well Differentiated ◽  
Ecog Ps

4036 Background: Gastrointestinal neuroendocrine tumors (NET) overexpress vascular endothelial growth factor (VEGF), thus we hypothesized that Bevacizumab (Bv), a monoclonal antibody targeting VEGF in combination with chemotherapy may show an activity in duodeno-pancreatic NET. Methods: This multicenter, open-label, non-randomized, two- group phase II trial assessed in one group the efficacy and safety of Bv (7.5 mg/kg IV on day 1, every 3 weeks), combined with 5-FU/streptozotocin (stz): 5-FU 400 mg/m²/d; Stz 500 mg/m²/d IV, d1-5/ every 42 days, during a minimum of 6 months in patients (pts) with progressive, metastatic, well-differentiated duodeno-pancreatic NET (WHO 2000), not previously treated with chemotherapy, ECOG PS ≤2 and Ki 67 index < 15%. Primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate, safety and quality of life. Study duration was 24 months. Results: In the ITT population, 34 pts were enrolled, 22 (64.7%) were men, median age 55.3 years (37.0-77.6), 33 (97.1%) pts had ECOG-PS 0/1. Most metastases were in the liver 33 (97.1%) pts or lymph nodes 14 (41.2%) pts. Ki-67 proliferative index was 0-2% in 8 (25%) pts, 3-4% in 5 (15.6%), 5-9% in 6 (18.8%), 10-14% in 12 (37.5%) and 15% in 1(3.1%) pt. Median treatment duration was 14.0 months; median number of cycles was 10. At 24 months, median PFS was 23.7 months [95%CI: 14.5; not reached] based on 18 events. PFS rate at 18 months was 62%. Tumor control rate was 100% (n= 34) including partial response in 19 (55.9%) pts and stable disease in 15 (44.1%) pts. Survival rate at 24 months was 88%. Median OS was not reached, 5 patients died. CTC grade 3/4 Adverse Events (AEs) occurred in 23 (67.6%) of pts, mainly digestive 5 (14.7%) pts. G3/4 Bv targeted AEs were hypertension in 7 (20.6%) pts and thromboembolism in 4 (11.8%). Conclusions: Efficacy data in this phase II trial assessing a novel approach with Bv and 5-FU/stz in duodeno-pancreatic NET is encouraging and the toxicity profile is acceptable. Results suggest that Bv may have a place in the treatment of pancreatic NET and warrant further investigation in a phase III trial.

Peripheral T-cell lymphomas unspecified presenting in the skin: analysis of prognostic factors in a group of 82 patients

Blood ◽  
2003 ◽  
Vol 102 (6) ◽  
pp. 2213-2219 ◽  
Author(s):  
Marcel W. Bekkenk ◽  
Maarten H. Vermeer ◽  
Patty M. Jansen ◽  
Ariënne M. W. van Marion ◽  
Marijke R. Canninga-van Dijk ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Size ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Skin Lesions ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
T Cell Lymphomas ◽  
Nor Phenotype ◽  
Peripheral T Cell Lymphomas

Abstract In the present study the clinicopathologic and immunophenotypic features of 82 patients with a CD30– peripheral T-cell lymphoma, unspecified, presenting in the skin were evaluated. The purpose of this study was to find out whether subdivision of these lymphomas on the basis of cell size, phenotype, or presentation with only skin lesions is clinically relevant. The study group included 46 primary cutaneous CD30– large cell lymphomas and 17 small/medium-sized T-cell lymphomas as well as 17 peripheral T-cell lymphomas with both skin and extracutaneous disease at the time of diagnosis. Patients with primary cutaneous small- or medium-sized T-cell lymphomas had a significantly better prognosis (5-year-overall survival, 45%) than patients with primary cutaneous CD30– large T-cell lymphomas (12%) and patients presenting with concurrent extracutaneous disease (12%). The favorable prognosis in this group with primary cutaneous small- or medium-sized T-cell lymphomas was particularly found in patients presenting with localized skin lesions expressing a CD3+CD4+CD8– phenotype. In the primary cutaneous T-cell lymphoma (CTCL) group and in the concurrent group, neither extent of skin lesions nor phenotype had any effect on survival. Our results indicate that peripheral T-cell lymphomas, unspecified, presenting in the skin have an unfavorable prognosis, irrespective of the presence or absence of extracutaneous disease at the time of diagnosis, cell size, and expression of a CD4+ or CD8+ phenotype. The only exception was a group of primary cutaneous small- or medium-sized pleomorphic CTCLs with a CD3+CD4+CD8– phenotype and presenting with localized skin lesions.

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