POLATUZUMAB VEDOTIN (POLA) + OBINUTUZUMAB (G) + LENALIDOMIDE (LEN) IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL): PHASE IB/II INTERIM ANALYSIS

2019 ◽  
Vol 37 ◽  
pp. 175-176 ◽  
Author(s):  
C. Diefenbach ◽  
B. Kahl ◽  
L. Banerjee ◽  
A. McMillan ◽  
R. Ramchandren ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Phase Ib

scholarly journals Safety Profile of Idelalisib in Patients with Refractory Follicular Lymphoma: Interim Analysis of a Noninterventional Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 48-50
Author(s):  
Gilles Salles ◽  
Ka Lung Wu ◽  
Sofya Kovalchuk ◽  
Santiago Mercadal ◽  
Annalisa Chiarenza ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Safety Profile ◽  
Interim Analysis ◽  
Research Funding ◽  
Stage Iii ◽  
Disease Stage ◽  
Stevens Johnson Syndrome ◽  
Risk Of Death ◽  
Registration Trial ◽  
Grade 3

Introduction: Idelalisib, a selective oral inhibitor of PI3Kδ, was approved by the FDA and EMA as monotherapy for patients with advanced follicular lymphoma (FL) based on positive efficacy and safety results from the registration phase 2 trial in patients with indolent non-Hodgkin lymphoma (iNHL) refractory to 2 prior regimens (NCT01282424; 101-09). Phase 3 studies of idelalisib in earlier lines of treatment for iNHL were terminated prematurely due to an increased risk of death and higher incidence of serious adverse events (AEs) associated with idelalisib. Herein, we present the preplanned interim results as of June 8, 2020, of the safety of idelalisib monotherapy in patients with refractory FL treated in the EU from one of the largest noninterventional trials of idelalisib. Methods: This was a noninterventional, partially retrospective cohort study conducted in 10 European countries (EUPAS19618; NCT03568929). Eligible patients were adults aged ≥18 years treated with idelalisib for refractory FL, per the Summary of Product Characteristics and treatment guidelines, in routine clinical practice. Data was collected from patients' medical records and anonymized. Safety events were evaluated and included treatment-emergent AEs (TEAEs), health outcomes of interest (HOIs) requested by the EMA (bowel perforations, Grade ≥3 diarrhea/colitis, progressive multifocal leukoencephalopathy, pneumonitis, Grade ≥3 rash, infections, Stevens-Johnson syndrome, transaminase elevations, and hepatocellular injury), and deaths. TEAEs were defined as AEs that occurred between first dose and 30 days after last dose. Data were summarized using descriptive statistics. Rates per person-year were calculated as the number of patients experiencing an AE divided by the person-time at risk. Results: For the 158 patients included in this analysis, median age was 67 years and 84 (53%) were male. A summary of patient and disease characteristics at baseline are presented in Table 1. At treatment initiation, 47 (30%) patients had grade 2 FL and 105 (66%) had Ann Arbor stage III/IV disease, though these characteristics were not captured for 42% and 20% of patients, respectively; 149 (94%) had ≥2 prior therapies. The median duration of idelalisib exposure was 165 (range 11-1321) days, and patients were observed for a median of 323 (range 12-1676) days. In total, 144 (91%) patients experienced a TEAE, with a rate of 3.36 per person-year. The proportion of patients experiencing Grade 3/4, severe, common, and HOI TEAEs are presented in Table 2. Diarrhea of any grade was the most common TEAE, and infections were the most common treatment-emergent HOI. During the TEAE period, 19 (12%) patients died (Table 2). The proportion of common TEAEs reported in this analysis were lower compared with a subgroup analysis of patients with FL from the registration trial (Salles Haematologica 2017; DOI: 10.3324/haematol.2016.151738), including diarrhea 27% vs 51%, cough 9% vs 32%, fever/pyrexia 10% vs 29%, pneumonia 5% vs 11%; treatment-emergent Grade 3/4 diarrhea/colitis and transaminase elevations were also lower in this analysis: 8% vs 17% and 4% vs 14%. This comparison is limited due to differences in study populations, namely that patients in the registration trial had more advanced disease (stage III/IV, 66% vs 83%) and had a higher median number of prior therapies (3 vs 4). Conclusions: This interim analysis of the safety of idelalisib in patients with refractory FL in this large noninterventional safety study provides an estimate of potential final study findings. The AE profile from this study appears to corroborate the known safety profile of idelalisib. No new safety signals were detected. Disclosures Salles: Bristol Myers Squibb: Consultancy, Other; Genmab: Consultancy; Gilead: Consultancy, Honoraria, Other: Participation in educational events; Epizyme: Consultancy; Abbvie: Consultancy, Honoraria, Other: Participation in educational events; Autolus: Consultancy; Amgen: Honoraria, Other: Participation in educational events; Celgene: Consultancy, Honoraria, Other: Participation in educational events; Debiopharm: Consultancy; Takeda: Consultancy, Honoraria, Other; Novartis: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria, Other; Janssen: Consultancy, Honoraria, Other: Participation in educational events; Karyopharm: Consultancy; Kite: Consultancy, Honoraria, Other; MorphoSys: Consultancy, Honoraria, Other. Pettengell:Celgene: Honoraria; MEI Pharma: Honoraria; Roche Ltd: Honoraria; Takeda: Honoraria. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Abbvie: Other: travel grants, Research Funding; Gilead: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Corradini:Kiowakirin: Consultancy, Honoraria; Incyte: Consultancy; Gilead: Consultancy, Honoraria, Other; F. Hoffman-La Roche Ltd: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Other; BMS: Other; Servier: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other; Kite: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other; Takeda: Consultancy, Honoraria, Other; AbbVie: Consultancy, Honoraria, Other. De Belder:Gilead Sciences Europe, Ltd.: Current Employment. Shah Gupta:Gilead Sciences, Ltd.: Current Employment. van Troostenburg:Gilead Sciences GmbH: Current Employment. Rajakumaraswamy:Gilead Sciences, Inc.: Current Employment. Ramroth:Gilead Sciences, Ltd.: Current Employment.

scholarly journals Interim analysis of a phase Ib study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild type melanoma progressing on prior anti-PD-L1 therapy

2019 ◽  
Vol 30 ◽  
pp. v554 ◽  
Author(s):  
S.K. Sandhu ◽  
V.G. Atkinson ◽  
M Gonzalez Cao ◽  
T. Medina ◽  
A Soria Rivas ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Wild Type ◽  
Phase Ib

Chimeric Anti-CD20 Monoclonal Antibody (Rituximab; Mabtheraâ) in Remission Induction and Maintenance Treatment of Relapsed /Resistant Follicular Non-Hodgkin’s Lymphoma : A Phase III Randomized Intergroup Clinical Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 586-586 ◽  
Author(s):  
Marinus H.J. Van Oers ◽  
Martine Van Glabbeke ◽  
Ivana Teodorovic ◽  
Cynthia Rozewicz ◽  
Richard Klasa ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Hodgkin’S Lymphoma ◽  
Maintenance Treatment ◽  
Initial Diagnosis ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Remission Induction ◽  
Non Hodgkin's Lymphoma

Abstract Background. In view of a) the efficacy of Rituximab (R) monotherapy in relapsed low grade lymphoma; b) the feasibility to combine R with cytostatic drugs c) the potential of such combinations to clear minimal residual disease, in 1999 we started a phase III clinical trial in patients with relapsed follicular non-Hodgkin’s lymphoma, with 2 main objectives. First: to compare CHOP and R-CHOP as to response rate and response quality. Second: to establish the effect of maintenance treatment with R on progression-free survival (PFS ). Study design. Patients with stages III or IV follicular lymphoma at initial diagnosis and relapsed after or resistant to a maximum of two non-anthracycline containing systemic chemotherapy regimens, were randomized to remission induction with either 6 cycles of standard CHOP (once every 3 weeks) or CHOP + R (375 mg /m2 at day 1 of each cycle of CHOP). Those with a complete or partial remission after 6 cycles of therapy underwent a second randomization to no further treatment or maintenance treatment with R (375 mg/m2 once every 3 months until relapse or for a maximum period of two years). Results. In February 2004, a preplanned second interim analysis by the IDMC was performed. At that time 461 patients had been included. Of these, 369 could be evaluated for response (188 CHOP; 181 R-CHOP). The groups did not differ as to age, sex, performance status, time from initial diagnosis, number and type of, and best overall response to prior chemotherapy. Both treatment arms yielded similar PR rates: CHOP 53.7%; R-CHOP 52.5 %. However, there was a highly significant difference in CR rates: CHOP 18.1% versus R-CHOP 30.4 % (p=0.0004). 319 patients have been randomized for maintenance treatment. Of these, 268 were evaluable (132 observation; 136 R maintenance). 1 year and 3 year PFS were 54.9% and 31.2% respectively in the observation arm, and 80.2 % and 67.7% in patients with R maintenance treatment (p< 0.0001). There is as yet no impact on OS: the observed difference (in favor of R maintenance) was not significant for an interim analysis (p=0.03). There were no differences in toxicity between CHOP and R-CHOP induction treatments. Maintenance treatment was associated with minimal toxicity. Because the planned second interim analysis revealed that the primary endpoints for both the induction and maintenance part of the study had been reached, the formal criteria for stopping the trial have now been met. Conclusion. In patients with relapsed/resistant follicular lymphoma R-CHOP remission induction results in a highly significant increase in CR rate as compared to CHOP. Moreover, this is the first trial to show that in these patients Rituximab maintenance treatment achieves a considerable improvement in PFS.

Tolerability and Efficacy of Bortezomib Added to CVP-R for Previously Untreated Advanced Stage Follicular Lymphoma: Interim Analysis of a Phase II Study by the NCIC Clinical Trials Group.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1576-1576 ◽  
Author(s):  
Laurie H Sehn ◽  
David A Macdonald ◽  
Sheldon H. Rubin ◽  
Morel Rubinger ◽  
Kevin R Imrie ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Interim Analysis ◽  
Standard Dose ◽  
Single Agent ◽  
Acceptable Level ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Open Label ◽  
Grade 3

Abstract Background: Despite recent improvements in therapy, follicular lymphoma (FL) remains incurable with standard treatment, warranting investigation of new approaches. Bortezomib, the first-in-class proteasome inhibitor has demonstrated promising efficacy as a single agent in heavily pretreated patients (pts) with FL. This is the first study to evaluate the safety and efficacy of the addition of bortezomib to cyclophosphamide, vincristine, prednisone and rituximab (CVP-R). Methods: This is a phase II multi-center open-label trial adding bortezomib (1.3 mg/m2 day 1&8) to standard dose C(750 mg/m2) V(1.4 mg/m2, capped at 2 mg) P(40 mg/m2 × 5) –R(375 mg/m2) for up to 8 cycles in pts with newly diagnosed stage III/IV FL requiring therapy. Planned accrual is 90 patients. A two-stage design was employed with a planned interim analysis of the first 28 patients to ensure an acceptable level of neurotoxicity (defined as less than 5/28 patients with grade 3/4 neurotoxicity after the first 4 cycles) and meaningful response rate (more than 12/28 patients with a complete response following 8 cycles), prior to enrolling remaining patients. Results: Median age of the first 28 patients was 55 years (range, 30–73). Fifty percent were male and 79% had stage IV disease. FLIPI score at study entry: low 14%, intermediate 43%, high 43%. Overall, the combination of bortezomib and CVP-R was extremely well tolerated. To date, no pts have developed grade 4 neurotoxicity and only 1/28 (4%) has developed grade 3 neurotoxicity within the first 4 cycles (neuropathic pain which resolved without need for treatment modification). The incidence of grade 1 and 2 neurotoxicity was 54% and 25% respectively. Only 3 pts discontinued therapy prematurely (2 pt refusal, 1 progressive disease). Ninety-four percent of planned bortezomib treatments in the first four cycles and 93% of vincristine doses were administered without dose reduction. Hematologic toxicity was mild, with no pts experiencing grade 3/4 anemia or thrombocytopenia. Only 2 episodes of febrile neutropenia occurred and no grade 3/4 infections were noted. Although it is too early to report on efficacy in this ongoing trial, response objectives for stage I have been met, and enrollment to stage 2 is underway. Conclusions: The addition of bortezomib to standard dose CVP-R is very well tolerated, with an acceptable level of neurotoxicity, without compromising the delivery of bortezomib or vincristine. This ongoing study will provide toxicity and efficacy data to facilitate the development of a planned phase III trial.

A Two-Stage Phase Ib Study to Investigate the Pharmacokinetics, Safety and Tolerability of Subcutaneous Rituximab In Patients with Follicular Lymphoma as Part of Maintenance Treatment

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2858-2858 ◽  
Author(s):  
Antonio Salar ◽  
Reda Bouabdallah ◽  
Christine McIntyre ◽  
Pakeeza Sayyed ◽  
Beate Bittner
Keyword(s):  
Adverse Events ◽  
Follicular Lymphoma ◽  
Patient Experience ◽  
Maintenance Treatment ◽  
Fixed Dose ◽  
Pharmacokinetic Parameters ◽  
Two Stage ◽  
Serious Adverse Events ◽  
Maximum Serum ◽  
Phase Ib

Abstract Abstract 2858 Rituximab-containing regimens have become the standard of care for patients suffering from various CD20-positive B-cell malignancies. Currently, rituximab is administered as an intravenous (IV) infusion over several hours. These long infusion times and the side effects related to the infusion were cited by some patients as uncomfortable consequences of the current therapeutic treatment. Furthermore, the required procedure to establish intravenous access is considered invasive and can be painful, particularly in patients with malignant diseases who are treated repeatedly. Subcutaneous (SC) administration could significantly simplify treatment, shortening administration to less than 10 minutes and improving patient experience. Recombinant human hyaluronidase (rHuPH20) has been developed and approved to improve dispersion and absorption of co-administered drugs. It has been combined with rituximab to allow injection volumes larger than 10 mL to be safely and comfortably administered SC. The aims of this Phase Ib study were to select the dose of a new SC rituximab formulation with rHuPH20 giving comparable exposure to IV rituximab and to assess its safety and tolerability in male and female follicular lymphoma (FL) patients during maintenance treatment. This presentation shows the stage 1 data of a two-stage randomized, open-label, multi-centre adaptive Phase Ib study. 124 patients have been randomized to one of four rituximab maintenance treatment groups: 16 patients IV control, 34 patients SC dose 1 [375 mg/m2], 34 patients SC dose 2 [625 mg/m2] and 40 patients SC dose 3 [800 mg/m2]. Prior to randomization, eligible patients were treated with at least one IV rituximab dose at 375 mg/m2 in the maintenance setting. For patients randomized to one of the SC cohorts, a single IV dose was replaced by an SC dose. Patients received rituximab either on a q2m or q3m regimen, as per local practice. Safety data are available from a total of 119 patients. Rituximab SC was generally well tolerated. No clinically significant observations or treatment-related serious adverse events have been reported. A total of 95 adverse events (AEs) were reported in 46 patients (39%). The most commonly documented AE was “administration-associated reaction” (AAR, including rash, erythema and mild discomfort). These AARs were reversible, predominantly mild in intensity and only 1 event necessitated any treatment (metoclopramide for nausea). Overall, the AE profile is not significantly different to that expected in patients treated with rituximab IV (after AAR, the most frequent events were gastrointestinal disorders and mild infections). Four serious adverse events (SAEs) were reported in 4 separate patients, all reported as unrelated to study medication. There were no AEs leading to death, withdrawal or treatment discontinuation. The total volume administered SC in each patient ranged between 4.4 – 15.0 mL. The average injection duration was 2 mL/min. Rituximab maximum serum concentrations in the SC cohorts occurred between Day 2 and Day 8 (48 h and 168 h). Pharmacokinetic parameters were linear with respect to dose over the range of SC doses administered (375, 625 and 800 mg/m2). Rituximab concentrations on Day 28 (C28) and the extent of serum exposure (AUC0-57) in patients administered 625 mg/m2 rituximab SC were comparable to those in patients administered the standard rituximab IV dose of 375 mg/m2 SC. In conclusion, subcutaneous rituximab can be delivered quickly, comfortably and safely while achieving serum exposure comparable to the approved intravenous formulation in FL patients during maintenance treatment. The patient experience was favourable. These results support further testing of subcutaneous rituximab and a fixed dose of 1400 mg rituximab SC has been selected for formal Ctrough non-inferiority testing in stage 2 of the trial. Disclosures: McIntyre: Hoffmann-La Roche Ltd.: Employment. Sayyed: Hoffmann-La Roche Ltd.: Employment. Bittner: Hoffmann-La Roche Ltd.: Employment.

Final Results of a Randomized Phase 2 Multicenter Study of Two Bortezomib Schedules In Patients with Recurrent or Refractory Follicular Lymphoma. Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study FL-05

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 768-768 ◽  
Author(s):  
Vincent Ribrag ◽  
Herve Tilly ◽  
Olivier Casasnovas ◽  
Andre Bosly ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Clinical Study ◽  
Follicular Lymphoma ◽  
Interim Analysis ◽  
Research Funding ◽  
Optimal Schedule ◽  
Dose Schedule ◽  
Open Label ◽  
Qualitative Comparison ◽  
Duration Of Response ◽  
Indolent Lymphomas

Abstract Abstract 768 Background: Bortezomib has previously demonstrated activity in indolent lymphomas including follicular lymphoma (FL). However, the optimal schedule, dose and precise activity of bortezomib in FL remain to be investigated. Aims: To evaluate the efficacy and tolerability of bortezomib in the treatment of advanced FL, but also using a qualitative comparison of two different dose schedules, based on safety, efficacy and dosing convenience to recommend a dose schedule for further clinical studies. Methods: This prospective, randomized, sequential, international, multicenter, 2-arm, non-comparative, open-label, clinical study was conducted from 08–2005 to 09–2008. The eligible subjects (follicular lymphoma grade 1–3, no CNS involvement, in relapse or refractory to previous therapy, ECOG 0–2, Absolute neutrophil count > 1000 cells/mL; Platelets > 50,000 cells/mL, Aspartate transaminase < 3 × ULN; Alanine transaminase < 3 × ULN; Total bilirubin < 2 × ULN; Creatinin level < 150 μmol/L, without known previous HIV serology) were randomized to receive either treatment in a 1:1 ratio. Treatment arm A patients (pts) received 1.5 mg/m2 bortezomib administered biweekly on days 1, 4, 8, and 11 of a 21-day cycle for 8 cycles. Treatment arm B pts received 1.6 mg/m2 bortezomib administered weekly on days 1, 8, 15, and 22 of a 35-day cycle for 6 cycles. Treatment allocation was stratified according to number of prior therapies (1 or 2 versus > 2) and time to progression (TPP) for the last given anti-lymphoma therapy (≤ 12 months versus > 12 months). Responses were assessed using 1999 IWG criteria. An interim analysis was planned after 15 evaluable pts randomized in each treatment arm; if only 5 subjects or fewer respond, the treatment arm was concluded to be ineffective and the treatment arm closed to inclusion; otherwise this treatment arm proceeded to include 50 pts. Results: 87 pts (51 [59%] men and 36 [41%] women) with median age of 65 years (range:40 to 77) were treated with bortezomib. Prior therapies were >2 in 62% and progression <12 months from last therapy in 49%. 30% previously received HDT with ASCT, and all of them were previously treated with immunotherapy. Arm B was closed to inclusion after interim analysis. After this interim analysis, the 6 patients still on therapy in this arm completed therapy according to arm A. 15/50 pts (32%) in arm A (bortezomib 1.5 mg/m2) and 8/37 pts (23%) in arm B (bortezomib 1.6 mg/m2) achieved a complete, unconfirmed complete or partial response at the end of treatment. Median duration of response was 16 (range 1–45) and 15 (1-39) months and PFS was 6 and 7.5 months for arms A and B, respectively. Most drug-related AEs (all grades, all cycles) were mild. AEs > grade 3 observed in more than 5% of pts were lymphopenia (25% both arms), thrombocytopenia (19% and 25% in arms A and B, respectively) and neutropenia (8% both arms). One pt died of possibly drug-related cardiac failure associated with hyponatremia. Conclusions: This study demonstrates tolerability and durable clinical benefit of bortezomib when given at 1.5 mg/m2 biweekly on a 21 days cycle in pts with recurrent or refractory FL. These results suggest recommending this dose schedule for further clinical study. Disclosures: Ribrag: LFB: Honoraria, Research Funding; servier: Research Funding; celgene: Research Funding; pfizer: Honoraria; novartis: Honoraria. Tilly:Amgen: Honoraria. Feugier:roche: Consultancy, Honoraria.

scholarly journals A Phase Ib Study of Obinutuzumab Combined with Lenalidomide for Relapsed/Refractory Follicular B-Cell Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4458-4458 ◽  
Author(s):  
Franck Morschhauser ◽  
Gilles Salles ◽  
Steven Le Gouill ◽  
Herve Tilly ◽  
Catherine Thieblemont ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Median Number ◽  
Fixed Dose ◽  
Unique Type ◽  
Phase Ib ◽  
Advisory Boards ◽  
Grade 3

Abstract BACKGROUND: Lenalidomide exerts anti-proliferative activity on lymphoma cells, enhances T- and NK-cell function, and improves ADCC. The combination of lenalidomide and rituximab (R2) has been shown to be synergistic in pre-clinical models and in patients with relapsed and first-line follicular lymphoma (FL). Obinutuzumab, a unique type II glycoengineered monoclonal anti-CD20 antibody with increased ADCC and increased direct cell death induction compared to rituximab, has shown promising efficacy in NHL. Combining obinutuzumab with lenalidomide might be even more efficient than R2 combination. In 2012, we started a phase Ib/II study to assess the safety and efficacy of this combination (ClinicalTrials.gov: NCT01582776, GALEN) for relapsed/refractory lymphoma patients. Here, we report the phase Ib part whose primary objective was to determine the maximum tolerated dose (MTD) of lenalidomide in combination with a fixed dose of obinutuzumab. METHODS: To identify the MTD of lenalidomide, four patient cohorts received escalating doses (10, 15, 20, and 25 mg) of daily oral lenalidomide on days 1-21 of a 28-day cycle for the first cycle and on days 2-22 of a 28-day cycle from cycles 2 to 6. Intravenous infusions of obinutuzumab at a flat dose of 1000mg were given on Days 8, 15, and 22 of the first cycle and at D1 of cycles 2 to 6 (total of 8 infusions). Steroid premedication was mandatory before first obinutuzumab infusion. All subjects were required to take daily aspirin (100 mg) for deep vein thrombosis (DVT) prophylaxis during study period. Subjects who were unable to tolerate aspirin and subjects with prior history of DVT or at high risk received low molecular weight heparin therapy or warfarin (coumadin) treatment. Dose was escalated in a 3+3 design based on dose limiting toxicity (DLT) assessment during cycle 1 RESULTS: 20 patients with FL ([10 mg: 7; 15 mg: 3; 20 mg: 6, 25 mg: 4] QD) were enrolled between Oct 2012 and Feb 2014 at 7 centers, 10 men/10 women, median age 64 (range, 39–80) years, 15 with Ann Arbor stage IV, median number of prior systemic therapies 2 (range, 1–5) and 8 were rituximab refractory. One patient was withdrawn before receiving any treatment due to neutropenia occurring at baseline screening. Median number of cycles was 6 (range, 1–6). We observed 163 AEs (87 grade 1; 53 grade 2; 21 grade 3; one grade 4 and one grade 5). The most common AEs (All grades, ≥20% patients) were neutropenia (10/19; 53%), constipation (10/19; 53%) asthenia (7/19; 37%), upper respiratory tract infection (7/19; 37%), rash/cutaneous eruption (5/19; 26%), cough (5/19; 26%), diarrhea (4/19 ; 26%) and fever (4/19, 21%). Grade (G) 3/4 AEs occurring in ≥2 patients only consisted in neutropenia (8/19; 42%). Infusion related reactions occurred in 3 patients and did not exceed grade 2. Four DLTs have occurred in 2 patients: one unexplained death (G5) at 10 mg in the setting of G3 worsening pleural effusion; another patient treated at 20 mg had G3 pulmonary infection with G3 hypokalemia, both deemed unrelated to study treatment. The MTD was not reached. Among 19 evaluable patients, 13 (68%) had an overall response according to Cheson 1999 criteria: 7 achieved CR, 3 CRu and 3 PR. CONCLUSION: Oral lenalidomide plus obinutuzumab is well tolerated and effective in patients with relapsed or refractory FL. Recommended dose of lenalidomide was established at 20mg based on the increased incidence of grade 3/4 neutropenia between cycle 2 and 6 at 25mg. The Phase II partis currently assessing theefficacy of lenalidomide (at 20 mg) in combination with obinutuzumab in 2 separate populations of patients: relapsed/refractory follicular lymphoma in one cohort and relapsed/refractory aggressive lymphoma (diffuse large B-cell lymphoma and mantle cell lymphoma) in another cohort. Disclosures Morschhauser: Celgene: advisory boards, advisory boards Other, Honoraria; Genentech/roche: Honoraria, travel grants Other. Off Label Use: obinutuzumab and lenlidomide in relapsed follicular lymphoma. Salles:celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; roche: advisory boards, advisory boards Other, Honoraria, Research Funding. Le Gouill:Roche: Consultancy. Tilly:Roche/Genetech: advisory boards, advisory boards Other, Honoraria; Celgene: advisory boards Other, Honoraria. Cartron:roche: Consultancy, Honoraria; celgene: Honoraria.

INTERIM ANALYSIS OF CENTRAL REVIEW OF END-OF-THERAPY PET IN FOLL12 TRIAL FOR FOLLICULAR LYMPHOMA

2019 ◽  
Vol 37 ◽  
pp. 393-393
Author(s):  
L. Guerra ◽  
F. Bergesio ◽  
A. Versari ◽  
A. Franceschetto ◽  
S. Peano ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Interim Analysis
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