A multicenter, open label, uncontrolled, phase II clinical trial evaluating the safety and efficacy of venetoclax in combination with atezolizumab and obinutuzumab in richter transformation of CLL.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS7575-TPS7575
Author(s):  
Marco Montillo ◽  
Davide Rossi ◽  
Emanuele Zucca ◽  
Anna Maria Frustaci ◽  
Stefano Pileri ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Response Duration ◽  
Lymphocytic Leukemia ◽  
Open Label ◽  
Expansion Phase ◽  
Safety And Efficacy ◽  
Prior Therapy ◽  
Heavily Pretreated ◽  
Ecog Ps

TPS7575 Background: Diffuse large B-cell (DLBCL) transformation from chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), Richter Syndrome (RS), has poor prognosis. Venetoclax, Bcl-2 inhibitor, has shown activity either in DLBCL and DLBCL-type RS. Atezolizumab is a humanized immunoglobulin monoclonal antibody (MoAb) targeting PD-L1 on tumor-infiltrating immune cells or tumor cells and prevents interaction with the PD-1 receptor and B7.1. Obinutuzumab, anti CD-20 MoAb compared to rituximab, presents a greater antibody-dependent cellular cytotoxicity, antibody-dependent cellular phagocytosis and direct cell death. Preliminary data of atezolizumab alone or in combination with obinutuzumab showed to be safe and promising in heavily pretreated DLBCL. We present a phase II trial evaluating safety and efficacy of venetoclax, atezolizumab, obinutuzumab combination in RS. Methods: Eligible pts are: ≥18 years, ECOG PS ≤2, diagnosis of DLBCL RS from CLL/SLL. Exclusion criteria: pretreated RS, prior therapy with venetoclax or atezolizumab, CNS involvement, history of autoimmune disease. The study consists of 2 phases. In the run-in phase 9 pts will be enrolled in three cohorts of 3 subjects each. If no more than 1 pt in each of the 3 groups experiences during the first 3 cycles: treatment-related death or grade 4 non-infective/non-hematologic adverse event; the expansion phase will follow enrolling up to 31 pts. Treatment consists of 35 cycles with: obinutuzumab (1000 mg C1-8), atezolizumab (1200 mg C1-18), venetoclax (400 mg/d C1-35). Primary endpoint of the study is safety and tolerability for the run-in phase; efficacy (overall response, complete remissions, response duration, progression free and overall survival) for the expansion phase. Safety and efficacy are also secondary endpoints of each phase. Exploratory consists of MRD monitored by flow cytometry and ultra-deep NGS of disease markers; correlation between outcome and disease biomarkers. EUDRACT 2018-005028-40. Clinical trial information: 2018-005028-40.

Long-term safety and efficacy of pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in relapsed and refractory multiple myeloma (RRMM) patients enrolled in the MM-002 phase II trial.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8588-8588 ◽  
Author(s):  
David Samuel DiCapua Siegel ◽  
Paul Gerard Guy Richardson ◽  
Ravi Vij ◽  
Craig C. Hofmeister ◽  
Rachid C. Baz ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Response Duration ◽  
Median Number ◽  
Open Label ◽  
Safety And Efficacy ◽  
Vein Thrombosis ◽  
Intent To Treat

8588 Background: MM-002 is a randomized, open-label, multicenter phase II trial evaluating the safety and efficacy of POM with or without LoDEX in advanced RRMM pts. Methods: Pts who had received ≥ 2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT), and were refractory to their last treatment were randomized to POM+LoDEX (POM 4 mg/day, days 1–21 of a 28-day cycle; LoDEX 40 mg/week) or POM alone. End points included progression-free survival (PFS), response rate (according to EBMT criteria and investigator assessment), response duration, overall survival (OS), and safety. The efficacy outcomes are based on the intent-to-treat population (POM+LoDEX, n = 113; POM, n = 108). Results: The median number of prior therapies in each group was 5 (range 1–13). In the POM+LoDEX arm, 30 (27%) pts had high-risk cytogenetics, including del(17p13) and/or t(4p16/14q32). The overall response rate (≥ partial response) was 34% and 15% with POM+LoDEX and POM, respectively, with a median duration of 8.3 (95% CI: 5.8–10.1) and 8.8 (95% CI: 5.5–11.4) mos, respectively. At least minimal response was observed in 45% and 31% of pts, respectively. Median PFS was 4.6 (95% CI: 3.6–5.5) and 2.6 (95% CI: 1.9–2.8) mos with POM+LoDEX and POM, respectively, with a median follow-up of 16.0 and 12.2 mos. Median OS was 16.5 (95% CI: 12.4–18.5) and 13.6 (95% CI: 9.6–18.1) mos, respectively. The most common treatment emergent Gr 3/4 adverse events (AEs) reported in the safety population (n = 219) were neutropenia (44%), anemia (23%), thrombocytopenia (21%), and pneumonia (18%); there were no reports of Gr 3/4 peripheral neuropathy. The incidence of deep-vein thrombosis was low (2%). AEs were managed through dose reductions or interruptions, and supportive care with G-CSF (52%), RBC transfusions (47%), and platelet transfusions (17%). Discontinuations due to AEs were 10%. Conclusions: POM with or without LoDEX is clinically effective and generally well tolerated in RRMM pts who have received multiple prior treatments, including LEN and BORT. AEs were predictable and manageable. Updated data will be presented at the meeting. Clinical trial information: NCT00833833.

Bevacizumab (Bmab) in combination with uracil-tegafur (UFT) and oral leucovorin (LV) in elderly patients (≥ 75 years old) with metastatic colorectal cancer (mCRC): A multicenter phase II trial (J-BLUE study).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 588-588
Author(s):  
Mitsuo Shimada ◽  
Tomohiro Nishina ◽  
Jun Higashijima ◽  
Toshikazu Moriwaki ◽  
Toshiki Masuishi ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Elderly Patients ◽  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Open Label ◽  
Effective Treatment Option ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Ecog Ps

588 Background: Now fluoropyrimidine plus Bmab is considered a recommendable option to the majority of elderly mCRC patients who are deemed inappropriate for the standard doublet chemotherapy with biologics. Our previous phase II study of UFT/ LV in elderly mCRC patients (≥75 years old) had demonstrated acceptable safety and efficacy (overall response rate [ORR] 33%, progression-free survival [PFS] 5.3 months, overall survival [OS] 18 months). The aim of the present study was to investigate the efficacy and safety of Bmab in combination with UFT/LV for elderly mCRC patients. Methods: This study was designed as a single-arm, open-label, multicenter, cooperative group (SGOSG-TCTG) clinical trial (trial registration: UMIN000003515). Key eligibility criteria included age ≥75 years, ECOG performance status (PS) 0 or 1, first-line chemotherapy, measurable lesions, and preserved organ functions. Patients received UFT 300mg/m2/day and LV 75mg/body/day on days 1-21 followed by 7 days rest, and intravenous administration of Bmab 5mg/kg on days 1 and 15. Treatment repeated every 28 days. The primary endpoint was PFS, and secondary endpoints were ORR, OS, and safety. Results: A total of 55 patients were enrolled from 15 institutions between Aug 2008 and Mar 2012. Among them, 52 eligible patients were evaluated. Median age was 80 years (range: 75-87). ECOG PS 0 was 73%. Median PFS was 8.2 months (95% confidence interval [CI], 6.2-10.3, events in 86.5%). Confirmed ORR was 40.4% (95% CI, 27.0-54.9%). Median OS was 18.7 months (95% CI, 10.3-27.0, events in 48%). The most common grade ≥3 treatment-related adverse events were hypertension (11.5%), fatigue (7.7%), nausea (5.8%), and diarrhea (5.8%). The treatment-related death occurred in 2 (3.8%) patients. Main reasons for discontinuation of treatment were disease-progression (62.5%) and toxicity (27.1%). Conclusions: Bmab in combination with UFT/LV is tolerable and effective treatment option for elderly patients (≥75 years old) with mCRC. Further trial with Bmab plus UFT/LV targeting elderly mCRC patients would be warranted. Clinical trial information: 000003515.

Phase 3 Randomized Trial of Fludarabine/Cyclophosphamide Chemotherapy with or without Oblimersen Sodium (Bcl-2 Antisense; Genasense; G3139) for Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 338-338 ◽  
Author(s):  
Kanti R. Rai ◽  
Joseph O. Moore ◽  
Thomas E. Boyd ◽  
Loree M. Larratt ◽  
Anatoliy K. Golenkov ◽  
...  
Keyword(s):  
Phase 1 ◽  
Single Agent ◽  
Chemotherapy Resistance ◽  
Response Duration ◽  
Response Assessment ◽  
Lymphocytic Leukemia ◽  
Phase 3 ◽  
Symptomatic Disease ◽  
Prior Therapy ◽  
Ecog Ps

Abstract Bcl-2 is an anti-apoptotic protein that has been closely linked to chemotherapy resistance and inferior survival in patients (pts) with CLL. Preliminary studies showed that oblimersen, an antisense oligonucleotide that targets Bcl-2, enhanced apoptosis induced by fludarabine (Flu), dexamethasone, and rituximab in cultured CLL cells. In a Phase 1 study, oblimersen displayed modest single-agent activity in CLL pts who had received extensive prior therapy. We conducted a randomized, multinational, Phase 3 trial of chemotherapy given with or without oblimersen in pts with advanced CLL. Eligibility included: symptomatic disease; intermediate or high-risk Rai stage; ≥ 1 Flu-containing regimen; ECOG PS ≤ 2; adequate organ function. Exclusions: stem cell/allogeneic transplant; autoimmune anemia/thrombocytopenia. Pre-randomization strata: prior treatment (1 or 2 vs. ≥ 3 regimens); response vs. refractory to prior Flu; and response duration to last therapy (> or ≤ 6 mos). All pts received Flu 25 mg/m2/d, plus cyclophosphamide (Cy) 250 mg/m2/d, daily for 3 days. Pts randomized to oblimersen received 3 mg/kg/d x 7 days by IV infusion, beginning 4 days before Flu/Cy and on each day of Flu/Cy treatment. Subsequent cycles were repeated every 28 days, for a maximum of 6 cycles, or to the time of CR, intolerable toxicity, or progression. All pts received prophylactic filgrastim, TMP/SMZ, and acyclovir. Response assessment was conducted at every cycle during treatment, and every 2 months thereafter for up to 36 months. The primary endpoint of the study was to compare the proportion of pts who achieved complete (CR) and nodular partial (nPR) responses. Secondary endpoints included: overall response rates (CR/nPR/PR); durable responses; response duration; time-to-progression; clinical benefit; and safety. Bone marrows in responding pts underwent central blinded review. A total of 241 pts were randomized; the last patient was enrolled in the 2nd quarter 2003. All pts have completed ≥ 1 year of follow-up, and results of this trial will be presented.

Efficacy and safety of duvelisib, a phosphoinositide 3 kinase (PI3K) δ and γ inhibitor, in Chinese patients (pts) with relapsed/refractory follicular lymphoma (R/R FL): A single-arm, open-label, multicenter, phase Ⅱ clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19532-e19532
Author(s):  
Zhong Zheng ◽  
Yuhuan Gao ◽  
Yongping Song ◽  
Ying Qian ◽  
Hongmei Jing ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Follicular Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Chinese Patients ◽  
Aggressive Lymphoma ◽  
Efficacy And Safety ◽  
Open Label ◽  
Prior Therapy ◽  
Best Response

e19532 Background: Follicular lymphoma (FL) is a common type of non-Hodgkin’s lymphoma with high rates of recurrence. The conventional therapy for R/R FL is not curative. Duvelisib is a potent inhibitor of both PI3K-δ and PI3K-γ that has been approved by the FDA for pts with R/R chronic lymphocytic leukemia, R/R small lymphocytic lymphoma, and R/R FL after at least two prior therapies. The current study aimed to evaluate the efficacy and safety of duvelisib in Chinese pts with R/R FL after at least two prior therapies. The current study aimed to evaluate the efficacy and safety of duvelisib in Chinese pts with R/R FL after at least two prior therapies. Methods: This was a single-arm, open-label, multi-center, phase Ⅱ clinical trial. Adult pts (ECOG ≤ 2) with histologically confirmed FL who have progressed on or relapsed after at least two prior therapies (at least one prior therapy was rituximab-contained regimen) were recruited. The main exclusion criteria were pts with grade 3b FL or those whose condition showed a propensity to transform to aggressive lymphoma. Duvelisib 25 mg was administered orally, twice daily in a 28-day cycle (max. 12 cycles) until disease progression, intolerable toxicity, death, or withdrawal. The primary endpoint was ORR as determined by Independent Review Committee (IRC) based on the revised International Working Group response criteria for Malignant Lymphoma (IWG 2007). Secondary endpoints included ORR reported by investigators as per IWG 2007; ORR reported by IRC and investigators as per Lugano 2014 criteria; DOR; PFS; OS; TTR; and safety outcomes. Results: 23 pts (22 R/R FL and 1 diffuse large B cell lymphoma) were enrolled and included in efficacy and safety analyses (last patient first dose was on Jun 30, 2020). The median age was 49 (range, 31-70) years, and 30% were females. At the data cut-off date (Dec 30, 2020), as per IWG 2007, the ORR reported by IRC was 83%, with a best response of 6 complete responses (CR) and 13 partial responses (PR); and the ORR reported by investigators was 78%, with a best response of 18 PR. As per Lugano 2014 criteria, the ORR was 83% by IRC (7 CR + 12 PR) and 78% by investigators (2 CR + 16 PR). Median DOR, PFS, and OS have not been reached. Median TTR was 1.8 (range, 1.6-5.5) months by IRC. Treatment-related adverse events (TRAEs) of any grade occurred in 21 (91%) of 23 pts, in which 12 (52%) were ≥ grade 3. The most common ( > 20%) TRAEs were neutropenia (16, 70%), increased alanine aminotransferase (11, 48%), increased aspartate aminotransferase (10, 44%), leukopenia (7, 30%), thrombocytopenia (6, 26%), increased lactate dehydrogenase (5, 22%), and rash (5, 22%). Conclusions: Duvelisib yielded impressive anti-tumor activity with manageable safety profiles in Chinese R/R FL pts and could be a compelling treatment option in this setting. Clinical trial information: NCT04707079.

A multicenter phase II study of erlotinib and bevacizumab in patients with metastatic melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8539-8539 ◽  
Author(s):  
K. Wyman ◽  
D. Spigel ◽  
I. Puzanov ◽  
J. Hainsworth ◽  
M. Kelley ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Metastatic Disease ◽  
Bowel Perforation ◽  
Progression Free Survival ◽  
Response Duration ◽  
Prior Therapy ◽  
Adequate Organ Function ◽  
Melanoma Patients ◽  
Ecog Ps

8539 Background: Erlotinib and bevacizumab have demonstrated activity in a number of malignancies by virtue of interrupting interdependent signaling pathways thought important in tumorigenesis. Melanoma may be an appropriate target based on its expression of EGFR and VEGF. We conducted a phase II multi-institutional trial evaluating erlotinib and bevacizumab in advanced melanoma patients. Methods: Eligibility included measurable disease, ECOG PS = 0–1, adequate organ function, no more than one prior therapy for metastatic disease, and CNS metastases were allowed if limited and controlled. Patients received oral erlotinib 150 mg/day and bevacizumab 10 mg/kg IV Q 2 weeks with tumor evaluation every 8 weeks. The primary outcomes were response rate (RR), response duration, and frequency of PFS >6 months. Secondary outcomes included overall survival, safety, and tolerability. A two-stage accrual design was employed ensuring that = 3/21 patients had PFS >6 months before additional patients were accrued. Results: As of Nov 2006, 29 patients with metastatic melanoma were enrolled. A total of 23 patients were evaluable for response. The majority was male 19/29 (65%) and had a median age = 62 yrs (range 35–78 years). Fifteen of the 29 had stage M1c disease (51.7%) and 18/29 (62.1%) had a PS = 1. Ten patients (34%) had prior adjuvant therapy and 6 patients (21%) prior therapy for metastatic disease. There were 2/23 (9%) partial responses lasting < 6 months and 5/23 (22%) had stable disease lasting > 6 months. The median progression free survival of evaluable patients was 96 days (95% CI: 50 - 142 days). A total of 25 grade III toxicities were observed with the most common being rash/pruritis (n=4), pain (n=4), fatigue (n=3), hypertension (n=2) and diarrhea (n=2). Two grade IV toxicities were observed (myocardial infarction and bowel perforation) both thought to be due to bevacizumab. Conclusion: The combination of erlotinib (150 mg/day) and bevacizumab (10 mg/kg) appears potentially active in patients with metastatic melanoma with largely tolerable toxicities. Accrual of a total of 41 patients will be completed shortly. [Table: see text]

Results of a randomized phase II trial of amrubicin (AMR) versus topotecan (Topo) in patients with extensive-disease small cell lung cancer (ED-SCLC) sensitive to first-line platinum-based chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8028-8028
Author(s):  
R. Jotte ◽  
P. Conkling ◽  
C. Reynolds ◽  
L. Klein ◽  
J. F. Fitzgibbons ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Single Agent ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Open Label ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
Platinum Based Chemotherapy ◽  
Ecog Ps

8028 Background: SCLC presents as ED-SCLC in 60%-70% of patients (pts). AMR, a synthetic anthracycline, is approved for these pts in Japan. We compare the efficacy and safety of single-agent AMR vs topotecan in non-Japanese pts with 2nd-line ED-SCLC sensitive to 1st-line platinum-based chemotherapy. Methods: This phase II, open-label, multicenter study enrolled pts with ED-SCLC sensitive to 1st-line platinum-based chemotherapy (recurrence or progression ≥90 days from 1st-line treatment). Pts aged ≥18 years with ECOG performance status (PS) ≤2 and only 1 prior therapy were eligible. Pts were randomized (2:1) to receive IV AMR 40 mg/m2/d (d, 1–3) or IV topotecan 1.5 mg/m2/d (d 1–5) and treated every 21 days until progression, unacceptable toxicity, or withdrawal. The primary endpoint, overall response rate (ORR, complete + partial response), used RECIST criteria. Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. Results: In all, 76 pts were randomized to AMR (n=50) or topotecan (n=26) with AMR given for a median of 6 cycles (range 1–16) and topotecan 3 cycles (1–16). AMR significantly improved ORR rates vs topotecan (p<0.012; Table ). Median PFS/OS was 4.3 months (95% CI 2.0, 6.1)/9.3 months (95% CI 5.7, 12.0) with AMR vs 3.5 months (95% CI 2.1, 6.3)/8.9 months (95% CI 4.8, 13.8) with topotecan. There was a higher proportion of ECOG PS 2 pts in the AMR group (n=6) vs the topotecan group (n=2). A trend towards improved OS was observed in the ECOG 0–1 subgroup of 68 pts: median OS was 10.5 months with AMR vs 9.7 months with topotecan. The most common grade ≥3 adverse events with AMR vs topotecan were neutropenia (53% vs 74%), thrombocytopenia (31% vs 52%) and leukopenia (27% vs 30%). Three AMR pts (6%) and 1 topotecan pt (4%) died of neutropenic infection. Conclusions: AMR significantly improves ORR and has acceptable tolerability as 2nd-line treatment in pts with sensitive ED-SCLC. [Table: see text] [Table: see text]

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