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.

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 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.

Promising Efficacy with the New Anti-CD20 Antibody GA101 In Heavily Pre-Treated NHL Patients – Updated Results with Encouraging Progression Free Survival (PFS) Data From a Phase II Study In Patients with Relapsed/Refractory Indolent NHL (iNHL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2868-2868 ◽  
Author(s):  
Gilles Andre Salles ◽  
Franck Morschhauser ◽  
Catherine Thieblemont ◽  
Philippe Solal-Céligny ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Survival Advantage ◽  
High Dose ◽  
Free Survival ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 2868 Background: GA101 is the first type II, glycoengineered and humanized monoclonal anti-CD20 antibody with Phase I results (NHL/CLL) (Salles, ASH 2008, 2009; Cartron, EHA 2009; Morschhauser, ASH 2009; Sehn, ASH 2009) and phase II results (Indolent NHL) previously reported (EHA 2010). Based on an additional 1 year follow-up period, we report updated efficacy and safety results with single agent GA101, presenting new and encouraging progression free survival (PFS) data indicating a survival advantage of those patients randomized to the high dose cohort (1600/800mg). Methods: 40 eligible patients were randomized to receive GA101 in a low-dose (LD, n=18) or a high dose (HD, n=22) cohort. GA101 was given on d1, d8, d22 and q21 days for total of 9 infusions. In the LD cohort, GA101 was given 400mg all infusions; in the HD cohort, d1 and d8 at 1600mg and 800mg for subsequent infusions. Primary endpoint was end of treatment response (EOR), assessed 4 weeks after last infusion (44 weeks after treatment start). Secondary objectives were safety, pharmacokinetics and PFS. Results: Patients (Table 1) were heavily pre-treated (median 3 prior therapies) with 55% of patients not responding to or relapsing within six months after a previous rituximab-containing regimen (rituximab refractory). There were no significant differences in demographics and baseline tumour burden between the two cohorts and 75% of patients completed all scheduled 9 infusions. EOR was 17% (3 PR, 6 SD, 7 PD, 2 UNK) in the LD cohort, and 55% (2 CR, 10 PR, 6 SD, 4 PD) in the HD cohort. Of note, 6/22 rituximab-refractory patients (5 HD, 1 LD) responded, with a EOR response of 50% in rituximab-refractory patients in the HD cohort (5/10). Responses occurred across all FcγIIIR genotypes in both cohorts: of 3 responders in LD, 2 patients with F/F genotype, other unknown; of 12 responders in HD; 5 F/F, 7 F/V. Responding patients from both LD and HD groups appeared to have higher GA101 plasma concentrations compared to non-responding patients. Median PFS was 6 months [1.1-16.9+ months] and 11.3 months [1.8-14.2+ months] for the LD and HD cohorts respectively (Hazard ratio 0.55 [95% CI 0.24;1.27]). Of 15 responding patients at EOR, 9 have an ongoing response in follow-up (LD=2, HD=7), with 2 PRs converting to CR (LD=1, HD=1) and another PR to CRu (HD). In addition 2 patients (LD=1, HD=1) in follow-up converted from EOR SD to PR, one patient with an ongoing response and the other subsequently relapsing, therefore 10 patients currently have an ongoing response. GA101 was well tolerated in both cohorts with the most common AEs being infusion related reactions (LD 72%, HD 73% of patients), mostly of G1-2. During treatment, related G3-4 hematological AEs were transient neutropenia (n = 3 in HD), febrile neutropenia (n=1 in HD) and thrombocytopenia (n = 1 in HD), four patients experienced at least one G3-4 Infection (LD n=1, HD n=3). Nine patients experienced a total 12 SAEs during treatment period, with 4 related to GA101 (HD n=4; herpes zoster, febrile neutropenia, pancreatitis, neutropenia) and 2 patients in the additional follow-up period, with SAEs of pyrexia (LD) and bacteraemia (HD), both unrelated to GA101. In addition, no B-cell recovery has been observed to date. Conclusion: GA101 single agent is well tolerated, with promising efficacy and provides very encouraging PFS data, in this group of heavily pre-treated relapsed and refractory iNHL patients, indicating a survival advantage for those patients in the HD cohort (1600/800mg). Disclosure: Salles: Roche: Consultancy, Honoraria. Morschhauser:Roche: Consultancy, Honoraria. Wenger:Roche: Employment. Birkett:Roche: Employment. Cartron:Roche: Consultancy, Honoraria; GSK: Honoraria.

Bendamustine, Bortezomib and Rituximab in Patients (pts) Relapsed/Refractory Indolent and Mantle Cell Non-Hodgkin Lymphoma (NHL): a Multicenter Phase II Clinical Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 924-924 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Julie M. Vose ◽  
Jennifer L Kelly ◽  
Faith Young ◽  
Jane Liesveld ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Research Funding ◽  
Varicella Zoster ◽  
Non Hodgkin Lymphoma ◽  
Multicenter Phase ◽  
Mantle Cell ◽  
Purine Analog ◽  
Heavily Pretreated

Abstract Abstract 924 Bendamustine (B) is an alkylating agent recently approved for relapsed and refractory indolent non-Hodgkin lymphoma NHL. In vitro studies suggest synergy between bendamustine and rituximab (R), and two phase II trials of this combination demonstrated tolerability and high response rates in indolent and mantle cell (MCL) NHL. The proteasome inhibitor bortezomib (Velcade; V) has significant single agent activity in indolent and mantle cell NHL. We have completed enrollment of a multicenter phase II trial combining bortezomib with the bendamustine/rituximab combination. Eligible pts had relapsed or refractory indolent or mantle cell NHL. Treatment consisted of B 90 mg/m2 day 1 and 4; R 375 mg/m2 day 1 and V 1.3 mg/m2 day 1, 4, 8, 11. Six 28-day cycles of therapy were planned. 31 patients (23 male) were enrolled; median age was 64 yrs (range 44-84). Histology included 16 follicular NHL, 7 MCL, 3 marginal zone NHL, 3 SLL and 2 lymphoplasmacytic NHL. Patients were heavily pretreated with a median of 4 prior regimens, including anthracycline containing chemotherapy (n=19), purine analog chemotherapy (n=6), ASCT (n=6), and radioimmunotherapy (n=9). 10 pts were refractory to rituximab and 25 pts had advanced stage disease at time of study. One pt never received therapy due to transformation. One pt died of sepsis after the first cycle of therapy. Common expected toxicities included thrombocytopenia, fatigue, fever, anemia, neutropenia and infusion reactions. Peripheral neuropathy was reported in 18 pts, including 2 with grade 3 neurotoxicity; additionally 14 patients reported constipation. There were 5 pts who developed varicella zoster reactivation (no prophylaxis given). Fourteen pts completed 6 cycles; reasons for premature withdrawal include progressive disease (PD), (n=4); cytopenias (n=4), infection (n=2), death (n=1) and nausea (n=1); 4 patients currently remain on treatment as of August 2009. Of 25 pts evaluable for response, overall response rate was 84% (95%CI 65%-94%). Best response following therapy was CR/Cru: 13 (52%); PR: 8 (32%); SD: 1(4%); PD: 3 (12%). Interestingly, 11/11 pts with FL responded to treatment (including 7 (64%) CR/CRu), and 5/7 pts with MCL responded to treatment. With a median follow-up of 13 months, 4 patients have died (3 of PD). There is no association between prior ASCT, radioimmunotherapy or purine analog chemotherapy and premature study withdrawal. There was also no association between rituximab sensitivity and response to BVR. Correlative laboratory studies are ongoing to determine predictors of toxicity and response. In summary, in this heavily pretreated population (as compared with prior studies of BR, including 33% rituximab-refractory pts), the BVR regimen is highly active, with over half of evaluable pts achieving CR/CRu. It appears more toxic than BR alone, with expected additive toxicities from V. Prophylaxis against varicella zoster reactivation is indicated when using this regimen. Further follow-up will determine whether the high CR/CRu rate corresponds to prolonged PFS. These promising results warrant additional evaluation of this regimen in de novo disease. Ultimately, a randomized trial will be necessary to determine the degree to which V adds efficacy to the BR combination. Disclosures: Friedberg: cephalon: Research Funding; millenium: Research Funding; genentech: LymphoCare Advisory Board. Off Label Use: bendamustine/bortezomib/rituximab combination therapy.

Promising Efficacy with the New Anti-CD20 Antibody GA101 In Heavily Pre-Treated NHL Patients – First Results From a Phase II Study In Patients with Relapsed/Refractory DLBCL and MCL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2878-2878 ◽  
Author(s):  
Guillaume Cartron ◽  
Catherine Thieblemont ◽  
Philippe Solal-Celigny ◽  
Franck Morschhhauser ◽  
Corinne Haioun ◽  
...  
Keyword(s):  
Treatment Period ◽  
Phase Ii ◽  
Single Agent ◽  
Plasma Concentrations ◽  
Progression Free Survival ◽  
Respiratory Arrest ◽  
High Dose ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 2878 Background: GA101 is the first type II, glycoengineered and humanized monoclonal anti-CD20 antibody with Phase I (Salles, ASH 2008, 2009; Cartron, EHA 2009; Morschhauser, ASH 2009; Sehn, ASH 2009) and indolent NHL phase II results (Salles, EHA, 2010) previously reported. Methods: Forty eligible patients [25 DLBCL/15 MCL] were randomized to receive GA101 in a low-dose (LD, n=21 [10 DLBCL/11 MCL]) or a high dose (HD, n=19 [15 DLBCL/4 MCL]) cohort. GA101 was given on d1, d8, d22 and q21 days for total of 9 infusions. In the LD cohort, GA101 was given 400mg all infusions; in the HD cohort, d1 and d8 at 1600mg and 800mg thereafter. Primary endpoint was end of treatment response (EOR), assessed 4 weeks after last infusion (44 weeks after treatment start). Secondary objectives were safety, pharmacokinetics and progression free survival (PFS). Results: Patients (Table 1) were heavily pre-treated (median 3 prior therapies), with 63% of patients not responding to or relapsing within six months after a previous rituximab-containing regimen (rituximab refractory) and 45% of patients completed all 9 infusions. For the LD cohort, EOR was 24% 5/21 (DLBCL – 2 PR, 1 CRu; MCL – 2 CR) and 32% (6/19) in the HD cohort (DLBCL – 4 PR; MCL – 2 PR). For DLBCL patients EOR was:28% (7/15) (1 CRu, 6 PR). For MCL patients EOR was: 27% (4/15) (2 CR, 2 PR). Of 13 refractory patients in LD, 1 patient achieved PR (8%) and of 12 refractory patients in HD, 3 patients achieved PR (25%), with two converting to CR during additional follow-up. Median PFS was 78 days [8-356+] and 83 days [7-428+] for the LD and HD cohorts respectively (Hazard ratio 0.88 [95% CI 0.43;1.79]).The most common AEs were G1-2 infusion related reactions (LD 81%, HD 68% of patients). Fourteen patients experienced at least one SAE during treatment period (LD=9, HD=5), with 7 related to GA101 (LD n=5, HD n=2), and 5 of these events associated with the first infusion (IRR=3; TLS=2), one after day 8 infusion (pyrexia), and one after cycle 6 infusion (bradycardia). During treatment, related G3-4 hematological AEs were transient neutropenia (n = 1 in HD), anemia (n = 2 in LD) and thrombocytopenia (n = 3 in LD). Ten patients had at least one G1-2 infection (5 in each cohort) with no G3-4 infections reported. GA101 plasma profiles were explored reflecting that mantle cell lymphoma patients in the HD (n=4) and LD (n=10) appeared to show lower plasma concentrations compared to DLBCL patients. There were 17 patient deaths reported (LD=11, HD=6), with 14 due to PD and 3 due to AE (1 during treatment period; cardio-respiratory arrest; not GA101-related) and two SAEs (LD) in follow-up (gastric haemorrhage, lung infection – both not GA101-related). Conclusion: In this group of heavily pre-treated DLBCL and MCL patients, single-agent GA101 was well tolerated with promising evidence of efficacy. Disclosure: Cartron: Roche: Consultancy, Honoraria; GSK: Honoraria. Morschhhauser:Roche: Honoraria. Birkett:Roche: Employment. Wenger:Roche: Employment. Asikanius:Roche: Employment. Salles:Roche: Honoraria.

Phase 2 study of rituximab in newly diagnosed stage IA nodular lymphocyte-predominant Hodgkin lymphoma: a report from the German Hodgkin Study Group

Blood ◽  
2011 ◽  
Vol 118 (16) ◽  
pp. 4363-4365 ◽  
Author(s):  
Dennis A. Eichenauer ◽  
Michael Fuchs ◽  
Annette Pluetschow ◽  
Beate Klimm ◽  
Teresa Halbsguth ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Early Stage ◽  
Progression Free Survival ◽  
Clinical Activity ◽  
Phase 2 ◽  
Newly Diagnosed ◽  
Antibody Treatment ◽  
Stage Ia ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) accounts for ∼ 5% of Hodgkin lymphoma cases. The disease is characterized by a strong CD20 expression on the malignant cells and a more indolent clinical course compared with classic HL. Anti-CD20 antibody treatment has shown clinical activity in relapsed NLPHL. In this phase 2 trial, we investigated rituximab in newly diagnosed stage IA NLPHL patients. Four weekly applications at 375 mg/m2 were given. Among the 28 evaluable patients, overall response rate was 100%, 24 patients (85.7%) achieved complete remission, and 4 (14.3%) achieved partial remission. At a median follow-up of 43 months, overall survival was 100%; progression-free survival at 12, 24, and 36 months was 96.4%, 85.3%, and 81.4%, respectively. No grade 3 or 4 toxicity was observed. Although treatment results with rituximab appear inferior compared with radiotherapy and combined-modality approaches in early-stage patients, investigation of anti-CD20 antibody-based combinations in NLPHL is warranted. This study was registered at www.clinicaltrials.gov as #NCT00346684.

scholarly journals Phase II study of oral fludarabine in combination with rituximab for relapsed indolent B-cell non-Hodgkin lymphoma

2009 ◽  
Vol 100 (10) ◽  
pp. 1951-1956 ◽  
Author(s):  
Kensei Tobinai ◽  
Ken-ichi Ishizawa ◽  
Michinori Ogura ◽  
Kuniaki Itoh ◽  
Yasuo Morishima ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Non Hodgkin Lymphoma
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