Obinutuzumab (GA101) in Patients With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma: Results From the Phase II GAUGUIN Study

2013 ◽  
Vol 31 (23) ◽  
pp. 2920-2926 ◽  
Author(s):  
Gilles A. Salles ◽  
Franck Morschhauser ◽  
Philippe Solal-Céligny ◽  
Catherine Thieblemont ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Group Versus ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Non Hodgkin Lymphoma ◽  
Flat Dose ◽  
End Of Treatment ◽  
Grade 3 ◽  
Anti Cd20

Purpose The phase II part of the phase I/II GAUGUIN study evaluated the efficacy and safety of two different doses of obinutuzumab (GA101), a type II, glycoengineered, humanized anti-CD20 monoclonal antibody, in patients with relapsed/refractory indolent non-Hodgkin lymphoma. Patients and Methods Patients were randomly assigned to receive eight cycles of obinutuzumab (GA101) as a flat dose of 400 mg on days 1 and 8 of cycle 1 and also on day 1 of cycles 2 to 8 (400/400 mg) or 1,600 mg on days 1 and 8 of cycle 1 and 800 mg on day 1 of cycles 2 to 8 (1,600/800 mg). Results Forty patients were enrolled, including 34 with follicular lymphoma; 38 of 40 patients had previously received rituximab and 22 of 40 were rituximab refractory. The overall response rate at the end of treatment was 55% (95% CI, 32% to 76%) in the 1,600/800-mg group (9% complete responders) and 17% (95% CI, 4% to 41%) in the 400/400-mg group (no complete responders). Five of 10 rituximab-refractory patients had an end-of-treatment response in the 1,600/800-mg group versus one of 12 in the 400/400-mg group. Median progression-free survival was 11.9 months in the 1,600/800-mg group (range, 1.8 to 33.9+ months) and 6.0 months in the 400/400-mg group (range, 1.0 to 33.9+ months). The most common adverse events were infusion-related reactions (IRRs) seen in 73% of patients, but only two patients had grade 3 to 4 IRRs (both in the 1,600/800-mg group). No IRRs were considered serious, and no patients withdrew for IRRs. Conclusion The 1,600/800-mg dose schedule of obinutuzumab (GA101) has encouraging activity with an acceptable safety profile in relapsed/refractory indolent non-Hodgkin lymphoma.

Phase II Study of Ofatumumab in Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report from the German Hodgkin Study Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2729-2729
Author(s):  
Dennis A. Eichenauer ◽  
Helen Goergen ◽  
Annette Pluetschow ◽  
Karolin Behringer ◽  
Stefanie Kreissl ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Antibody Treatment ◽  
Non Hodgkin Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for approximately 5% of all Hodgkin lymphoma (HL) cases. One hallmark of NLPHL is the consistent expression of CD20 on the malignant lymphocyte predominant (LP) cells. To shed more light on the role of anti-CD20 antibody treatment in relapsed NLPHL, we conducted a phase II study evaluating the fully humanized anti-CD20 antibody ofatumumab in 28 patients. Treatment consisted of 8 weekly doses (week 1: 300 mg, week 2-8: 1000 mg) of the antibody. Results: The median age of study patients was 45 years (range: 22-68) and the majority were male (64%). A median of 1 line of therapy (range: 1-5) had been applied prior to study treatment and 7/28 patients (25%) already had rituximab-containing treatment. At the final restaging 3 months after the end of treatment, response was documented in 27/28 patients (96%; 95%-CI: 84%-100%). After a median follow-up of 26 months, 1-year and 2-year progression-free survival (PFS) estimates were 93% and 80%, respectively. No patient died. Transformation into aggressive non-Hodgkin lymphoma (NHL) occurred in 2/28 patients (7.1%). No grade III/IV toxic events were observed. Conclusion: In summary, the anti-CD20 antibody ofatumumab represents a highly active and well tolerated treatment option in relapsed NLPHL. Longer follow-up is required for final conclusions. Disclosures Off Label Use: Ofatumumab in lymphocyte-predominant Hodgkin lymphoma. von Tresckow:Takeda: Consultancy; Celgene: Other: honoraria for preparation of scientific educational events; Novartis: Consultancy, Other: Travel and accomodation, Research Funding; Amgen: Other: honoraria for preparation of scientific educational events. Borchmann:Millennium: Research Funding. Engert:Takeda: Consultancy, Research Funding.

Phase II Study of Rituximab in Newly Diagnosed Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A Report From the German Hodgkin Study Group (GHSG)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2711-2711
Author(s):  
Dennis A. Eichenauer ◽  
Michael Fuchs ◽  
Annette Pluetschow ◽  
Beate Klimm ◽  
Teresa Halbsguth ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Ia ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 2711 Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) accounting for about 5% of cases. The clinical course is usually more indolent than in classical HL (cHL) resulting in an excellent long-term prognosis. This is particularly true for patients diagnosed with early-stage NLPHL representing the majority of cases. However, current standard treatment consisting of chemotherapy and/or radiotherapy (RT) is associated with an increased risk of late toxicity. Thus, there is a need for novel treatment strategies. Since CD20 is consistently expressed on the malignant lymphocyte-predominant (LP) cells, anti-CD20 antibody treatment appears to be a promising option. After impressive response rates were reported in relapsed NLPHL patients, the German Hodgkin Study Group (GHSG) initiated a trial to evaluate the anti-CD20 antibody rituximab in newly diagnosed stage IA NLPHL without clinical risk factors. Methods: Between June 2006 and October 2007, 29 patients from 23 sites were enrolled in this multicenter phase II trial. Study entry was restricted to adult patients (age 18 to 75) with biopsy-proven stage IA NLPHL without clinical risk factors. Treatment consisted of four weekly infusions of the anti-CD20 antibody rituximab at a dose of 375 mg/m2. Efficacy endpoints included remission status as assessed by computed tomography (CT) four weeks after completion of treatment, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) at two years; feasibility endpoints were acute treatment-related toxicities, adverse events, dose reductions and therapy delays. Results: Twenty-eight patients were eligible for the final analysis of this phase II trial; 71.4% of patients were male, 72% had supradiaphragmatic disease and the median age was 40 years. Treatment was conducted in the outpatient setting in the majority of cases. Rituximab was well tolerated; no grade III/IV toxicities were observed. Transfusions of erythrocytes or platelets were not required. At final restaging four weeks after the last rituximab application, 24 patients (85.7%) were in CR/CRu and four patients (14.3%) had partial remission (PR). Thus, overall response rate (ORR) was 100%. After a median follow-up of 43 months, all patients were still alive. Progression-free survival rate estimates at two, three and four years were 85.3%, 81.4% and 77.1%, respectively. Seven patients (25%) have relapsed and two patients developed secondary solid tumors. All patients with NLPHL relapse were successfully salvaged. Conclusions: The results of the present trial confirm the previously reported excellent response of NLPHL patients to rituximab. However, with a relapse rate of 25% at a median observation time of 43 months, rituximab does not seem to be as effective as RT alone or combined-modality strategies in stage IA NLPHL patients. Nonetheless, anti-CD20 antibodies have a favorable toxicity profile and may be offered to selected patients who are at particular risk for long-term side effects such as secondary malignancies. In addition, the combination of anti-CD20 antibodies and chemotherapy may also improve efficacy and decrease toxicity of NLPHL treatment in early unfavorable, advanced or relapsed disease. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study

2015 ◽  
Vol 33 (30) ◽  
pp. 3467-3474 ◽  
Author(s):  
Laurie H. Sehn ◽  
Andre Goy ◽  
Fritz C. Offner ◽  
Giovanni Martinelli ◽  
M. Dolores Caballero ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hodgkin Lymphoma ◽  
Randomized Study ◽  
Progression Free Survival ◽  
Final Analysis ◽  
Phase Iii ◽  
Indolent Lymphoma ◽  
Previous Response ◽  
Non Hodgkin Lymphoma ◽  
Anti Cd20

Purpose Obinutuzumab (GA101), a novel glycoengineered type II anti-CD20 monoclonal antibody, demonstrated responses in single-arm studies of patients with relapsed/refractory non-Hodgkin lymphoma. This is the first prospective, randomized study comparing safety and efficacy of obinutuzumab with rituximab in relapsed indolent lymphoma. The primary end point of this study was the overall response rate (ORR) in patients with follicular lymphoma after induction and safety in patients with indolent lymphoma. Patients and Methods A total of 175 patients with relapsed CD20+ indolent lymphoma requiring therapy and with previous response to a rituximab-containing regimen were randomly assigned (1:1) to four once-per-week infusions of either obinutuzumab (1,000 mg) or rituximab (375 mg/m2). Patients without evidence of disease progression after induction therapy received obinutuzumab or rituximab maintenance therapy every 2 months for up to 2 years. Results Among patients with follicular lymphoma (n = 149), ORR seemed higher for obinutuzumab than rituximab (44.6% v 33.3%; P = .08). This observation was also demonstrated by a blinded independent review panel that measured a higher ORR for obinutuzumab (44.6% v 26.7%; P = .01). However, this difference did not translate into an improvement in progression-free survival. No new safety signals were observed for obinutuzumab, and the incidence of adverse events was balanced between arms, with the exception of infusion-related reactions and cough, which were higher in the obinutuzumab arm. Conclusion Obinutuzumab demonstrated a higher ORR without appreciable differences in safety compared with rituximab. However, the clinical benefit of obinutuzumab in this setting remains unclear and should be evaluated within phase III trials.

Weekly Temsirolimus and Bortezomib For Relapsed Or Refractory B-Cell Non-Hodgkin Lymphoma: A Wisconsin Oncology Network Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3035-3035 ◽  
Author(s):  
Timothy S. Fenske ◽  
KyungMann Kim ◽  
Chong Zhang ◽  
John P. Farnen ◽  
Adedayo A. Onitilo ◽  
...  
Keyword(s):  
Partial Response ◽  
Adverse Events ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Mtor Inhibitors ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

Abstract Background Proteosome inhibitors and mammalian target of rapamycin (mTOR) inhibitors are each known to have activity for various B-cell malignancies, and affect distinct cellular pathways. Preclinical data show synergy between bortezomib and various mTOR inhibitors, supporting this combination in non-Hodgkin lymphoma (NHL). We conducted a phase II trial of temsirolimus and bortezomib in relapsed and refractory B-cell NHL, using a weekly dosing scheme that was previously tested in multiple myeloma (Ghobrial et al, Lancet Oncology, 2011; 263-272). Methods Wisconsin Oncology Network study HO10407 is a single-arm phase II study of IV bortezomib and temsirolimus for patients with relapsed and refractory B-cell NHL. A 35 day cycle was employed with bortezomib given at 1.6 mg/m2 and temsirolimus given at 25 mg IV weekly on days 1, 8, 15, and 22. Initially temsirolimus was also given on day 29 but, due to a high rate of thrombocytopenia, after the first 14 patients were enrolled the protocol was amended and the day 29 temsirolimus dose was removed. Patients were enrolled from 10 sites within the Wisconsin Oncology Network. The primary endpoints were overall response rate (ORR) and progression-free survival (PFS). The secondary endpoints were to determine safety, tolerability, complete response (CR) rate, duration of response (DOR), and overall survival (OS). Results Forty patients were enrolled between February 2011 and May 2013; however one patient withdrew consent immediately after enrollment and was never treated. We are therefore reporting results for 39 patients. The median age was 68, with 72% male. NHL subtypes consisted of diffuse large B-cell lymphoma (DLBCL, n=17), follicular lymphoma (FL, n=10), mantle cell lymphoma (MCL, n=7), small lymphocytic lymphoma (SLL, n=3), and marginal zone lymphoma (MZL, n=2). Patients received a median of 4 prior therapies (range 1 to 11). Three patients were previously treated with bortezomib, one of whom was refractory to a prior bortezomib-containing regimen. As of July, 24, 2013, two patients remained on protocol therapy. The median number of cycles given was 3. Out of 39 patients, CR was achieved in 3 patients (7.7% (95% CI: 1.6% - 21%)), partial response (PR) in 9 patients (23% (95% CI: 11% - 39%)), and stable disease in 9 patients (23% (95% CI: 11% - 39%)). The ORR was therefore 12/39 (31% (95% CI: 17-48%)). Among responders, the DOR ranged from 1.7 to 13.8 months, with a median DOR of 8.5 months (95% CI: 2.9-11.5). The median PFS was 4.7 months (95% CI: 2.1-7.8). The ORR for DLBCL was 18% (3/17, with 2 CR), for FL was 50% (5/10, with no CR), and for MCL was 57% (4/7, with 1 CR). In one patient, protocol therapy led to a partial response which served as a bridge to allogeneic stem cell transplantation. Grade 3/4 adverse events were experienced by 69% of patients. The grade 3/4 adverse events that occurred in at least 10% of patients were anemia (13%), lymphopenia (15%), neutropenia (23%), thrombocytopenia (38%), and gastrointestinal toxicities (15%). Conclusions In this phase II study, the combination of temsirolimus and bortezomib demonstrated activity in a group of heavily pre-treated patients. In some patients dramatic responses were seen, including two DLBCL patients who achieved complete remission after having previously progressed following autologous hematopoietic cell transplantation. Toxicities were manageable and treatment was delivered on an outpatient basis. Further studies with this combination or other proteosome inhibitor + mTOR inhibitor combinations are warranted in specific subtypes of NHL. Disclosures: Fenske: Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy. Off Label Use: Use of the combination of bortezomib and temsirolimus for relpased and refractory B-cell non-Hodgkin lymphoma. Ahuja:Bayer healthcare pharmaceuticals: Consultancy. Kahl:Millennium: Consultancy.

First Analysis of a Phase II Study of Rituximab-Gemcitabine, Cyclophosphamide, Vincristine and Prednisolone (R-GCVP) for Diffuse Large B Cell Lymphoma (DLBCL) Patients Considered Unsuitable for Anthracycline Containing Chemo-Immunotherapy. An NCRI Lymphoma Clinical Studies Group Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1634-1634
Author(s):  
Paul Fields ◽  
Andrew Webb ◽  
Christopher FE Pocock ◽  
William Townsend ◽  
Paul Smith ◽  
...  
Keyword(s):  
Overall Survival ◽  
Ejection Fraction ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Overall Response ◽  
End Of Treatment ◽  
Grade 3

Abstract Abstract 1634FN2 Introduction: The treatment of patients with DLBCL who are unsuitable for anthracycline containing chemotherapy remains a clinical challenge. Gemcitabine is a nucleoside analogue which has proven efficacy in the relapse setting in both non Hodgkin's and Hodgkin's lymphoma. We therefore developed a protocol incorporating Gemcitabine in a first line approach combined with CVP-R chemo-immunotherapy in DLBCL patients considered unfit for anthracycline containing chemotherapy. Methods: We performed a prospective, multicentre phase II trial in patients with DLCBL who were considered unfit for anthracycline containing chemo-immunotherapy. Eligibility criteria included ejection fraction < 50%, or ejection fraction ≥ 50% but with the presence of attendant significant co-morbidities (including: ischaemic heart disease, hypertension, diabetes mellitus), and ECOG PS 0–3. Patients received 6 cycles of Rituximab (375 mg/m2 IV D1), Cyclophosphamide (750mg/m2 IV D1), Vincristine (1.4 mg /m2 IV D1), Prednisolone (100mg, orally D1–5) and Gemcitabine IV D1 and D8. The Gemcitabine dose, if tolerated was sequentially escalated from 750mg/m2 in cycle 1 to 875mg/m2 in cycle 2 to 1000mg/m2 in cycle 3 with the dose maintained at 1000mg/m2 for cycles 4–6. Cycles were repeated every 21 days with growth factor support administered on day 9 of each cycle (pegfilgrastrim 6mg s/c).The primary endpoint was to achieve an overall response rate of > 40% assessed by CT scan at the end of treatment according to the Cheson criteria. Secondary endpoints were progression free survival and overall survival. Results: 62 patients were recruited from 32 UK sites over a 28 month period from April 2008 to July 2010. 66% were male. Median age was 76 years (range 52–90), 48 (77%) were > 70 years. 43 (69%) had stage III/IV disease and 46 (72%) had high – intermediate or high IPI (3–5) disease. ECOG performance status was ≥ 2 in 50% patients. Left ventricular ejection fraction (LVEF) was < 50% in 28 patients (45%). The 34 patients with LVEF ≥ 50% had significant co-morbidities, 22 (65%) had multiple co-morbidities. 44 (70%) received ≥ 3 cycles of treatment, reasons for early termination of treatment in the remaining 18 patients were progression (n=2), toxicity (n=5), death (n=6) patient choice (n=1) and other (n=4). 29 patients (47%) received the full 6 cycles. A total of 250 treatment cycles were delivered. Of the 44 patients who received ≥ 3 cycles of treatment, the dose of Gemcitabine was escalated to the full dose (1000mg/m2) in 67%. Day 8 Gemcitabine was delivered in 215/250 (86%) cycles of treatment. The overall response rate (CR/CRu/PR) at end of treatment for all 62 patients was 60%. For patients who received ≥ 3 cycles of treatment (n =44) the ORR was 79.5% at the end of treatment. There was no significant difference in ORR between those with LVEF <50% and those with LVEF ≥ 50% (71% vs 53%, p=0.155). At a median follow up of 18.2 months the 1 year progression free survival rate for all patients was 52.9% (95% CI 39.4–64.8). The 1 year overall survival (OS) rate is 62.4% (95% CI 48.5–73.6). For the group with LVEF <50% OS was 70.8% (95% CI: 48.4, 84.9) and LVEF group ≥ 50% OS was 55.9% (95% CI 37.1–71).Grade 3/4 haematological toxicity was observed in 54.1% patients. Grade 3/4 infection was observed in 24.6% of patients. The death rate observed related to infection for the whole cohort was 11%. Conclusion: This multicentre trial demonstrates that the R-GCVP regimen delivers excellent overall response rates with durable remissions in a group of patients where anthracycline use was precluded. The efficacy attained in this difficult group of patients provides a platform for testing the regimen in subsequent randomised phase II and phase III studies to confirm its efficacy. Disclosures: No relevant conflicts of interest to declare.

A multicenter phase II study of bendamustine with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8023-8023 ◽  
Author(s):  
Michinori Ogura ◽  
Kiyoshi Ando ◽  
Nozomi Niitsu ◽  
Seok Jin Kim ◽  
Ken Ohmachi ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Salvage Regimen ◽  
Prior Therapy ◽  
Non Hodgkin Lymphoma ◽  
Grade 3

8023 Background: Effective salvage therapies are needed in patients (pts) with relapsed/refractory DLBCL after R-CHOP. Therapy with bendamustine plus rituximab (B-R) was well tolerated and effective in the preceding phase I study in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, including DLBCL. This phase II study assessed the efficacy and safety of B-R in pts with relapsed/refractory DLBCL. Methods: Pts with histologically confirmed DLBCL (excluding transformed disease) and 1-3 prior therapies received rituximab 375 mg/m2 IV on day 1 and bendamustine 120 mg/m2 IV on days 2 and 3 of each 21-day cycle, for up to 6 cycles. Recovery of neutrophil count to ≥1,000/mm3 and platelet count to ≥75,000/mm3 were required prior to the start of each cycle; treatment delays >2 weeks resulted in discontinuation. The primary endpoint was overall response rate (ORR); secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and safety. Results: A total of 63 pts were enrolled; data from 59 pts were available. Median age was 67 (range, 36-75) years with 37 pts over 65 years. The majority of pts (64.4%) had 1 prior therapy; 57 pts (96.6%) were previously treated with rituximab-containing combination chemotherapy and 8 (13.6%) had prior auto-PBSCT. Pts received a median of 4 (range, 1-6) treatment cycles. Sixteen (27.1%) pts completed 6 treatment cycles; most common reasons for early discontinuation were disease progression (n=15) and failure to meet criteria to start the next cycle (n=13). Among 59 pts evaluable for response, ORR was 62.7% with a 37.3% CR rate. The median PFS was 200 days (95% CI, 109-410). Most common grade 3/4 adverse events (AEs) included CD4 lymphocytes decreased (66.1%), neutropenia (54.2%), and thrombocytopenia (10.2%). Four (6.8%) pts discontinued due to serious AEs (cytomegalovirus infection, infection, pneumonia, and pneumonia/respiratory failure). Conclusions: B-R demonstrated promising activity in pts with relapsed/refractory DLBCL. Toxicity was primarily hematologic and generally manageable. These results suggest that B-R is a promising salvage regimen for pts with relapsed/refractory DLBCL after R-CHOP.

scholarly journals DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma

2019 ◽  
Vol 37 (11) ◽  
pp. 912-922 ◽  
Author(s):  
Ian W. Flinn ◽  
Carole B. Miller ◽  
Kirit M. Ardeshna ◽  
Scott Tetreault ◽  
Sarit E. Assouline ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Oral Treatment ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Open Label ◽  
Dual Inhibitor ◽  
Non Hodgkin Lymphoma ◽  
Phosphoinositide 3 Kinase

PURPOSE Indolent non-Hodgkin lymphoma (iNHL) remains largely incurable and often requires multiple lines of treatment after becoming refractory to standard therapies. Duvelisib was approved by the Food and Drug Administration for relapsed or refractory (RR) chronic lymphocytic leukemia or small lymphocytic lymphoma (SLL) and RR follicular lymphoma (FL) after two or more prior systemic therapies. On the basis of the activity of duvelisib, a first-in-class oral dual inhibitor of phosphoinositide 3-kinase-δ,-γ, in RR iNHL in a phase I study, the safety and efficacy of duvelisib monotherapy was evaluated in iNHL refractory to rituximab and either chemotherapy or radioimmunotherapy. PATIENTS AND METHODS Eligible patients had measurable iNHL (FL, SLL, or marginal zone B-cell lymphoma) double refractory to rituximab (monotherapy or in combination) and to either chemotherapy or radioimmunotherapy. All were treated with duvelisib 25 mg orally twice daily in 28-day cycles until progression, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) using the revised International Working Group criteria for malignant lymphoma. RESULTS This open-label, global phase II trial enrolled 129 patients (median age, 65 years; median of three prior lines of therapy) with an ORR of 47.3% (SLL, 67.9%; FL, 42.2%; MZL, 38.9%). The estimated median duration of response was 10 months, and the estimated median progression-free survival was 9.5 months. The most frequent any-grade treatment-emergent adverse events (TEAEs) were diarrhea (48.8%), nausea (29.5%), neutropenia (28.7%), fatigue (27.9%), and cough (27.1%). Among the 88.4% of patients with at least one grade 3 or greater TEAE, the most common TEAEs were neutropenia (24.8%), diarrhea (14.7%), anemia (14.7%), and thrombocytopenia (11.6%). CONCLUSION In the DYNAMO study, oral duvelisib monotherapy demonstrated clinically meaningful activity and a manageable safety profile in heavily pretreated, double-refractory iNHL, consistent with previous observations. Duvelisib may provide a new oral treatment option for this patient population of which many are elderly and in need of additional therapies.

scholarly journals Overall Survival Benefit in Patients With Rituximab-Refractory Indolent Non-Hodgkin Lymphoma Who Received Obinutuzumab Plus Bendamustine Induction and Obinutuzumab Maintenance in the GADOLIN Study

2018 ◽  
Vol 36 (22) ◽  
pp. 2259-2266 ◽  
Author(s):  
Bruce D. Cheson ◽  
Neil Chua ◽  
Jiri Mayer ◽  
Greg Dueck ◽  
Marek Trněný ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin Lymphoma ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Primary Analysis ◽  
Intention To Treat ◽  
Non Hodgkin Lymphoma ◽  
Grade 3 ◽  
Overall Survival Benefit

Purpose To perform an updated analysis of the randomized phase III GADOLIN trial in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated with obinutuzumab (GA101; G) and bendamustine (B). Patients and Methods Patients with histologically documented, rituximab-refractory CD20+ indolent non-Hodgkin lymphoma received G 1,000 mg (days 1, 8, and 15, cycle 1; day 1, cycles 2 to 6) plus B 90 mg/m2/d (days 1 and 2, all cycles) or B 120 mg/m2/d monotherapy. Patients who did not experience disease progression with G-B received G maintenance (1,000 mg every 2 months) for up to 2 years. The primary end point was progression-free survival (PFS). Results Of 413 randomly assigned patients (intention-to-treat [ITT]: G-B, n = 204; B monotherapy, n = 209), 335 had follicular lymphoma (FL; G-B, n = 164; B monotherapy, n = 171). After a median follow-up of 31.8 months, median PFS in ITT patients was 25.8 months (G-B) and 14.1 months (B monotherapy; hazard ratio [HR], 0.57; 95% CI, 0.44 to 0.73; P < .001). Overall survival (OS) also was prolonged (HR, 0.67; 95% CI, 0.47 to 0.96; P = .027). PFS and OS benefits were similar in patients with FL. Grade 3 to 5 adverse events (AEs) were reported by 148 (72.5%) and 133 (65.5%) patients in the G-B and B monotherapy arms, respectively, most commonly neutropenia (G-B, 34.8%; B monotherapy, 27.1%), thrombocytopenia (10.8% and 15.8%), anemia (7.4% and 10.8%), and infusion-related reactions (9.3% and 3.4%). Serious AEs occurred in 89 G-B patients (43.6%) and 75 B monotherapy patients (36.9%); fatal AEs occurred in 16 (7.8%) and 13 (6.4%), respectively. Conclusion This updated analysis confirms the PFS benefit for G-B shown in the primary analysis. A substantial OS benefit also was demonstrated in the ITT population and in patients with FL. Toxicity was similar for both treatments.

Phase II Trial of Weekly Paclitaxel for Unresectable Angiosarcoma: The ANGIOTAX Study

2008 ◽  
Vol 26 (32) ◽  
pp. 5269-5274 ◽  
Author(s):  
Nicolas Penel ◽  
Binh Nguyen Bui ◽  
Jacques-Olivier Bay ◽  
Didier Cupissol ◽  
Isabelle Ray-Coquard ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Weekly Paclitaxel ◽  
Curative Intent ◽  
Free Survival ◽  
Grade 3

Purpose The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma. Patients and Methods Thirty patients were entered onto the study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m2 on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles. Results The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities. Conclusion Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.

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