A phase II study of enzalutamide (Enz) with dutasteride (Dut) or finasteride (Fin) in men ≥ 65 years with hormone-naive systemic prostate cancer (HNSPCa): Tolerability and geriatric asssessment (GA) results.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e16518-e16518
Author(s):  
Jason Zittel ◽  
Chunkit Fung ◽  
Dilip Sankar Babu ◽  
Elizabeth A. Guancial ◽  
Deepak M. Sahasrabudhe ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Older Men ◽  
Geriatric Depression ◽  
Grade 5 ◽  
Common Grade ◽  
Grade 3

e16518 Background: Older men are at a high risk for adverse events (AEs) from androgen deprivation therapy (ADT). In this phase II study, we evaluated Enz and Dut/Fin in lieu of ADT for at-risk older patients with HNSPCa. Methods: Eligible patients were ≥65 years (y); at high risk of AEs from ADT by GA or treating physicians; metastatic (M1) or non-metastatic (M0) HNSPCa with a PSA doubling time ≤ 9 months and testosterone > 50ng/dl. They received Enz 160 mg/day and Dut 0.5 mg/day or Fin 5 mg/day until disease progression. GA was performed at baseline and week (wk) 61 and/or at the time of progression. GA included validated tests: Instrumental Activities of Daily Living (IADL), fall history, Short Physical Performance Battery (SPPB), Geriatric Depression Scale (GDS), and Montreal Cognitive Assessment (MOCA). The prevalence of impairment for each assessment was calculated; change in prevalence from baseline to wk 61 was analyzed using paired sample t-test. Results: 43 patients were enrolled in the study. Median age at enrollment was 78 y (range 66-94) and 93% were ECOG 0-1; 37% (n = 16) had M0 and 63% (n = 27) had M1 HNSPCa, with the majority (67%) having Gleason 6 or 7 disease. At baseline, 18.6% met the cutoff for impairment for IADLs, 53.7% for SPPB, 7.9% for GDS and 64.3% for MOCA; 9.8% had a recent fall. Median baseline PSA was 11.38 ng/ml (range: 2-145). At the time of analysis, 29 men (67.4%) remain on study treatment. 95.3%, 74.4% and 46.5% of patients reported at least one Grade 1, 2 or 3 AE respectively. No patient had a Grade 4 AE and one Grade 5 AE was reported but was an unrelated event. The most common Grade 3 AEs were hypertension (27.8%), GI (19.4%), and cardiac (8.3%); all Grade 3 GI AEs reported were deemed unrelated to the study drugs. Only impairment in ≥ 1 IADL showed a statistically significant increase in prevalence at wk 61 of treatment (40.6%) compared to baseline (18.6%, p = 0.036). Conclusions: For older men with HNSPCa, Enz with Dut/Fin demonstrated efficacy with reasonable toxicity profile, and no significant impact on the majority of GA domains. Clinical trial information: NCT02213107.

scholarly journals Phase II Study of Lenalidomide and Rituximab As Salvage Therapy for Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

2013 ◽  
Vol 31 (5) ◽  
pp. 584-591 ◽  
Author(s):  
Xavier C. Badoux ◽  
Michael J. Keating ◽  
Sijin Wen ◽  
William G. Wierda ◽  
Susan M. O'Brien ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Phase Ii ◽  
Salvage Therapy ◽  
Phase Ii Study ◽  
Venous Thromboembolic Event ◽  
Febrile Episode ◽  
Lymphocytic Leukemia ◽  
Common Grade ◽  
Venous Thromboembolic ◽  
Grade 3

Purpose Lenalidomide is an immunomodulatory drug active as salvage therapy for chronic lymphocytic leukemia (CLL). We combined lenalidomide with rituximab to improve response rates in patients with relapsed or refractory CLL. Patients and Methods Fifty-nine adult patients (age 42 to 82 years) with relapsed or refractory CLL were enrolled onto a phase II study of lenalidomide and rituximab. Patients had received prior fludarabine-based therapy or chemoimmunotherapy. Rituximab (375 mg/m2 intravenously) was administered weekly during cycle one and on day 1 of cycles three to 12. Lenalidomide was started on day 9 of cycle one at 10 mg orally and administered daily continuously. Each cycle was 28 days. Rituximab was administered for 12 cycles; lenalidomide could continue indefinitely if patients benefitted clinically. Results The overall response rate was 66%, including 12% complete responses and 12% nodular partial remissions. Time to treatment failure was 17.4 months. Median overall survival has not been reached; estimated survival at 36 months is 71%. The most common grade 3 or 4 toxicity was neutropenia (73% of patients). Fourteen patients (24%) experienced a grade 3 to 4 infection or febrile episode. There was one episode of grade 3 tumor lysis; one patient experienced renal failure during the first cycle of therapy, and one venous thromboembolic event occurred during the study. Conclusion The combination of lenalidomide and rituximab is active in patients with recurrent CLL and warrants further investigation.

Long-Term Follow Up Of a Randomized Phase II Study Of The JAK2-Selective Inhibitor Fedratinib (SAR302503) In Patients With Myelofibrosis (MF)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4047-4047 ◽  
Author(s):  
Animesh Pardanani ◽  
Ayalew Tefferi ◽  
Catriona HM Jamieson ◽  
Nashat Y Gabrail ◽  
Claudia Lebedinsky ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Progression ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Hematologic Toxicity ◽  
Costal Margin ◽  
Spleen Volume ◽  
Randomized Phase Ii ◽  
Grade 3

Abstract Background We previously reported that patients with MF enrolled in a randomized Phase II study of fedratinib (SAR302503) (ARD11936; NCT01420770) had clinically meaningful reductions in splenomegaly and improvements in MF-associated constitutional symptoms after 24 weeks of treatment (Haematologica 2013;98:S1113). Here, we report updated efficacy and safety results from this study after 48 weeks of treatment (end of Cycle 12). Methods Patients with intermediate risk-2 or high-risk MF were randomized to receive once-daily fedratinib at doses of 300 mg, 400 mg, or 500 mg, for consecutive 4-weekly cycles, until disease progression or unacceptable toxicity. Eligible patients were aged ≥18 years, with palpable splenomegaly (5 cm below costal margin), and a platelet count ≥50 × 109/L. The primary measure for this study was percent change in spleen volume from baseline at the end of Cycle 3 (Blood 2012:120;Abstract 2837. Haematologica 2013;98:S1113). Endpoints for the current analysis included spleen response (≥35% reduction in spleen volume from baseline, assessed by a blinded independent central review by MRI), safety, and changes in bone marrow fibrosis (BMF). Results A total of 31 patients were randomized and treated: median age 63 years, 52% male, 58% primary MF, 58% high-risk MF, 90% JAK2V617F positive. The median numbers of treatment cycles were 12, 14, and 13 in the 300 mg, 400 mg and 500 mg dose groups, respectively, with median durations of exposure of 48.2, 56.2, and 52.4 weeks. At the cut-off date for this analysis, 21 patients (68%) remained on treatment; the most common reasons for treatment discontinuation were adverse events (AEs) (n=5) and withdrawal of consent (n=2). Overall, 58% (18/31) of patients achieved a spleen response at any time during treatment. The median spleen response duration was >35 weeks at all doses (Table). At Week 48, a spleen response was achieved by 30% (3/10), 80% (8/10), and 45% (5/11) of patients in the 300 mg, 400 mg, and 500 mg groups, respectively. Responses were generally maintained across all treatment groups. From Week 24 to Week 48 two additional patients achieved a spleen response (both in the 400 mg group), while one patient in the 500 mg group did not maintain a response (this patient had a fedratinib dose reduction to 200 mg). Changes in BMF up to Week 48 are being evaluated. The most common non-hematologic AE was diarrhea, with a Grade 3 rate of 13% (4/31 patients) but no Grade 4 cases were recorded. The rates of diarrhea decreased after the first cycle of treatment; from Cycle 2, the incidence of diarrhea (any grade) did not exceed 16% (5/31) at any cycle, and only one case of diarrhea was reported at Week 48 (end of Cycle 12). Anemia was the most-common hematologic toxicity, with a Grade 3 rate of 58% (18/31); no Grade 4 cases were reported. All Grades thrombocytopenia occurred in 55% (17/31) of patients, Grade 3 in three patients, and Grade 4 in two patients. Discontinuation of treatment due to AEs occurred in five patients over the 48 weeks (300 mg [n=2]; 400 mg [n=2]; 500 mg [n=1]), with two cases reported after Week 24 (dyspnea and leukocytosis [400 mg]; anemia and thrombocytopenia [500 mg]). There were 2 deaths (one in the 300 mg group due to unknown reasons [85 days after fedratinib discontinuation] and one in the 500 mg group due to disease progression [36 days after fedratinib discontinuation]). No cases of leukemic transformation were reported. Conclusions This updated analysis of the ARD11936 Phase II trial shows that treatment with fedratinib results in durable reductions in splenomegaly in patients with MF. No additional safety signals were observed with prolonged exposure to fedratinib. This study was sponsored by Sanofi. Disclosures: Pardanani: Sanofi, Bristol Myers Squibb, PharmaMar and JW Pharma: Clinical trial support Other. Jamieson:J&J, Roche: Research Funding; Sanofi: Membership on an entity’s Board of Directors or advisory committees. Lebedinsky:Sanofi: Employment. Gao:Sanofi: Employment. Talpaz:Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Research Funding; Novartis, Bristol-Myers Squibb, Ariad, Deciphera: Speakers Bureau.

Randomized, open-label, phase II study comparing five-weekly S-1 plus cisplatin (SP) with tri-weekly capecitabine plus cisplatin (XP) in chemotherapy-naïve patients with HER2 negative advanced gastric cancer (AGC): OGSG 1105 HERBIS-4A trial.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 102-102
Author(s):  
Atsushi Takeno ◽  
Youichi Makari ◽  
Shunji Endo ◽  
Jin Matsuyama ◽  
Ryohei Kawabata ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Open Label ◽  
Group 13 ◽  
Common Grade ◽  
Open Label Phase ◽  
Secondary Endpoints ◽  
Grade 3 ◽  
To Receive

102 Background: This phase II study aimed to investigate the safety and efficacy of XP compared to SP in the first-line treatment of HER2 negative AGC. Methods: Patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2 on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2 twice daily for 14 days plus cisplatin 80 mg/m2 on day 1, every 3 weeks). Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), time to treatment failure (TTF), and adverse events. Results: 84 eligible patients were randomly assigned to receive SP ( N = 41) or XP ( N = 43). No statistical difference was observed in overall RR between the SP and XP groups [51.2% (95% CI, 35.1% to 67.1%) vs. 53.5% (95% CI, 37.7% to 68.8%), P = 1.000]. Despite not significant, however, SP vs. XP showed a trend toward better PFS [median, 5.9 months vs. 4.1 months; hazard ratio (HR), 0.763; 95% CI, 0.462 to 1.259; P = .284] and OS (median, 13.5 months vs. 10.0 months; HR, 0.776; 95% CI, 0.485 to 1.244; P = .290). This trend in the SP vs. XP comparison was more pronounced in TTF (median, 4.5 months vs. 3.1 months; HR, 0.651; 95% CI, 0.421 to 1.006; P = .052). Common grade 3 to 4 hematological toxicities were neutropenia and anemia (SP group, 23% and 23%; XP group, 35% and 28%). Grade 3-4 anorexia and hyponatremia were more frequently seen in the XP group (31% and 16%) compared to the SP group (13% and 5%). Treatment-related deaths occurred in one patient (2.3%) in the XP group. Conclusions: XP failed to demonstrate the superior efficacy over SP. Higher incidence of severe toxicities by XP suggests SP as the standard 1st line chemotherapy for HER2 negative AGC in Japan. Clinical trial information: UMIN000006755.

Phase II study of postperative radiotherapy (RT), cisplatin (Ci), and cetuximab (Ce) in resected bad prognostic head and neck squamous cell carcinoma (HNSCC): Toxicity analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e16051-e16051
Author(s):  
Karen Benezery ◽  
Christian Righini ◽  
Emmanuel Chamorey ◽  
Benjamin Lallemant ◽  
Herve le Caer ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Oral Cavity ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Disease Free Survival ◽  
Incomplete Resection ◽  
Common Grade ◽  
Prospective Phase ◽  
Grade 3 ◽  
The Impact

e16051 Background: Despite toxic multimodal about 60% of resected HNSCC relapse. The addition of both Ce or Ci to RT improved overall survival of patients with HNSCC. Consequently, we designed a prospective phase II study, to evaluate the feasibility and efficacy of concomitant RT-Ci and Ce in bad prognostic resected HNSCC. Methods: Patients have resected HNSCC of the oral cavity , oropharynx, larynx or hypopharynx, and at least one of the following adverse prognostic factors: microscopically incomplete resection, >2 metastatic lymph nodes and/or >1 lymph node with extracapsular spread, vascular and/or lymphatic emboli, >2 perineural invasion, positive margins and pT4. All patients received: RT 70-72Gy in 7 weeks concurrent with Ce 250mg/m² weekly (6-7 weeks), after a loading dose of 400mg/m², and Ci 75mg/m² every 3 weeks x3 cycles. The primary endpoint is the 2 years disease-free survival. Results: 45 patients (35 Male) were enrolled, and 44 were evaluable for toxicity. Median age was 56 years (27-70). The tumor site was oral cavity (21), oropharynx (17), hypopharynx (3) and larynx (4). 39% of the patients had stage T2, 14% stage T3 and 27% stage T4. The nodal status was 0-2b in 80% of cases. The main adverse prognostic factors were the nodal involvement and microscopical positive resection (80% of patients). The RT-Ce-Ci regimen was discontinued in 11 cases including 7 due to toxicity. Among the 352 cycles (ie Ce+/-Ci) initially planned, 301 were delivered. Cutaneous and mucosal toxicity were the most common grade 3/4 side effects, accounting for 35% and 33%, respectively, and remained manageable. Grade 3 lymphopenia has been noted in 25% of cases. No treatment-related death was recorded. Conclusions: The triple association of RT-Ce-Ci appears to be safe and feasible in patients with bad prognostic resected HNSCC. The toxicity profile is comparable to that reported for RT-Ci or RT-Ce alone. Longer follow-up is required to evaluate the impact of addition of Ce to RT-Ci on survival.

A phase II study of Recchia's immunomodulatory schedule (RIS) as a maintenance therapy in high-risk tumors after a response.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3074-3074
Author(s):  
Manuel Sureda ◽  
Joseba Rebollo ◽  
Begona Vazquez ◽  
Pere Bretcha ◽  
Rosa Cañon ◽  
...  
Keyword(s):  
High Risk ◽  
Solid Tumors ◽  
Phase Ii ◽  
Low Dose ◽  
Residual Disease ◽  
Phase Ii Study ◽  
Interleukin 2 ◽  
Induced Response ◽  
Response To Chemotherapy ◽  
Grade 3

3074 Background: F. Recchia et al. (Interleukin-2 and 13-cis retinoic acid in the treatment of minimal residual disease: A phase II study. Int J Oncol. 20: 1275-1282, 2002) previously defined the possibility of achieving a chronic immune stimulation through a prolonged low dose sc interleukin 2 (IL2)-based schedule, leading to a prolongation of PFS in advanced cancer patients (pts). A confirmatory phase II study was started. Methods: Pts diagnosed of high risk solid tumors in response to chemotherapy were included. RIS consisted in low dose IL2 (1.8 MU sc per day, 5 days per week, 3 weeks per month) plus oral isotreonin (CRA, 0.5 mg/kg) the same days of IL2 and/or sc PEG-interferon (50 µg per week of treatment). No Chx was allowed with RIS, but concurrent maintenance with TKI or Hx was permitted. Results: Since 08/2007 to 01/2013, 69 pts (39 M/30 F, median age 60 y, range 31-78) were included. 51 pts were treated with stage IV disease. 36 pts entered in complete response (CR), 29 in partial response (PR), 1 with progressive disease, 3 adjuvant. 4/69 grade 3/4 toxicity, (6%): 1 fatal poliserositis resistant to cortisone after 20 months of RIS, 1 stopped RIS for reaction requiring steroids, 1 for multiinfarction dementia, 1 for grade 3 liver toxicity. 3 pts presented other alterations managed along the course of the RIS (1 PVT, 1 ITP, 1 angina resolved after stent placement). Grade 1-2 fever, fatigue and joint pain were commonly observed but usually controlled with NSAIDs. Among the 68 pts evaluable for response, one pt progressed, 26 presented stable disease (median TTP 3 mo, range 2-28), 3 presented PR (1 melanoma, 1 prostatic ca, 1 ovarian ca; 9, 11 and 28 mo respectively), and 38 maintained or presented CR (median TTP 19 mo, range 2-62+). Three pts in PR were converted to a CR during RIS (1 pancreatic ca, 1 ovarian ca, 1 larynx ca). Conclusions: In this study we confirm the previous results reported by F. Recchia et al. RIS represents a good alternative for high risk pts with solid tumors after systemic chemotherapy induced response with acceptable tolerability and offers in selected pts a possibility of obtaining a CR after a PR. Further validation and randomized studies are warranted.

scholarly journals Accuracy of 12 short versions of the Geriatric Depression Scale to detect depression in a prospective study of a high-risk population with different levels of cognition

2019 ◽  
pp. 1-10
Author(s):  
Simona Sacuiu ◽  
Nazib M. Seidu ◽  
Robert Sigström ◽  
Therese Rydberg Sterner ◽  
Lena Johansson ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
High Risk ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Depression Symptoms ◽  
High Risk Population ◽  
Geriatric Depression ◽  
Risk Population ◽  
Optimal Criterion ◽  
Short Versions

ABSTRACT Objectives: To determine the accuracy of 12 previously validated short versions of the Geriatric Depression Scale (GDS) to detect major depressive disorder (MDD) in a high-risk population with and without global cognitive impairment. Design: Cross-sectional study. Setting: Five hospitals, Western Sweden. Participants: Older adults (age ≥70 years, n = 60) assessed at a home visit 1 year after hospital care in connection with suicide attempt. Measurements: Depression symptoms were rated using the established 15-item GDS. Eleven short GDS versions identified by a recent systematic review were derived from this administered version. Receiver operating characteristic curves and area under the curve (AUC) for the identification of MDD diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, were obtained for each version. The Youden Index optimal criterion was used to determine the appropriate cutoffs. Analyses were repeated after stratification by cognitive status (Mini Mental State Examination score ≤24 and >24) for the best performing GDS short versions and the established 15-item GDS. Results: The 7-item GDS according to Broekman et al. (2011), with a cutoff 3, was the most accurate among the 12 short versions (AUC 0.90, 95% confidence interval 0.80–1.00), identifying MDD with sensitivity 88% and specificity 81%. The cutoff score remained consistent in the presence of global cognitive impairment, which was not the case for the standardized 15-item GDS. Conclusion: The Broekman 7-item GDS had high accuracy to detect MDD in this prospective clinical cohort at high risk for MDD. Further testing of GDS short versions in diverse settings is required.

scholarly journals Efficacy and Safety of Newer Targeted Immunotherapy for Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5650-5650
Author(s):  
Shehroz Aslam ◽  
Rida Riaz ◽  
Mustafa Nadeem Malik ◽  
Abdul Rafae ◽  
Warda Faridi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Common Grade ◽  
Grade 3 ◽  
Phase Iii Studies ◽  
Ongoing Phase ◽  
Targeted Immunotherapy

Abstract Introduction: Targeted immunotherapy includes monoclonal antibodies, antibody-drug conjugates and chimeric antigen receptor T-cells (CAR-T cells). With recent advancements, the study of novel agents that target various cellular receptors involved on myeloma cells, have been actively pursued. The main aim of our study is to review and summarize published literature on the efficacy and safety of these targeted immunotherapies in patients (pts) with multiple myeloma (MM). Methods: We performed a comprehensive literature search on articles published after 2012 using the following databases (Pubmed, Embase, Cochrane, Web of Science and Clinicaltrials.gov). We included 6 completed and 16 ongoing phase II, III trials involving both newly diagnosed MM (NDMM) as well as relapsed/refractory MM (RRMM) pts. Results: Siltuximab: We included 3 phase II trials of Siltuximab (S) involving 243 pts. One hundred ninety-one pts had RRMM while 52 pts had NDMM. The overall response rate (ORR) was 45.50 % and 88% in RRMM and NDMM pts respectively. In a phase II trial involving 52 transplant ineligible NDMM pts, S (11mg/kg) in combination with bortezomib (V), melphalan (M) and prednisolone was given. In 49 evaluable pts, the ORR was 88% with complete response (CR) in 27% pts, very good partial response (VGPR) in 71% pts, and partial response (PR) in 61% pts. The median progression-free survival (mPFS) was 17 months (mo) while the overall survival (OS) at 1 year (y) was 88%. The most common grade 3 and 4 adverse effects (AEs) were neutropenia (62%), thrombocytopenia (44%), pneumonia (17%), and anemia (13%). In a phase II trial involving 142 pts with RRMM, S (6mg/kg) in combination with V was given. The number (no.) of prior therapies were 1-3. In 131 evaluable pts, ORR was 55% with CR in 11% pts and PR in 44% pts. The mPFS was 8 mo (p=0.345) while the OS at 1 y was 81%. The most common grade 3 and 4 AEs were neutropenia (49%), and thrombocytopenia (48%). In another phase II trial involving 49 pts with RRMM, S (6mg/kg) in combination with dexamethasone (D) was given. The median no. of prior therapies was 4. In 47 evaluable pts, the ORR was 19% while the mPFS and OS were 3.7 mo (95% CI= 2.8-4.9) and 20.4 mo (95% CI= 11.4-32.3) respectively. The most common grade 3 and 4 AEs were neutropenia (36.7%), thrombocytopenia (53%), anemia (32.6%), leukopenia (8%), and fatigue (16.3%). Only one ongoing phase II study was found (Table 2). No phase III studies were found. Isatuximab (SAR650984): In a phase II trial involving 97 pts with RRMM, escalating doses of isatuximab (3-20 mg/kg) were given. The median age of pts was 62.5 y. The median no. of prior therapies was 5. At dose ≥10 mg/kg, maximum ORR of 24% was observed. The most common AEs were nausea (33%), fatigue (30%), dyspnea (26%), and cough (24%). Two ongoing phase II studies and 3 ongoing phase III studies were found (Table 2). Pembrolizumab and nivolumab: In a phase II study involving 48 pts with RRMM, pembrolizumab (200mg) in combination with pomalidomide and D was given. The median no. of prior therapies was 3. The ORR was 60% with CR in 8.33% pts, VGPR in 19% pts, and PR in 33% pts. The mPFS was 17.4 mo. The most common grade 3 and 4 AEs were neutropenia (42%), thrombocytopenia (13%), anemia (21%), and lymphopenia (15%). Two ongoing phase II/III studies each was found for Pembrolizumab. One ongoing phase II and III study each was found for nivolumab (Table 2). Tabalumab: In a phase II trial involving 148 pts with RRMM, tabalumab (100-300mg) in combination with D and V was given. The ORR was 58.1-59.5%. The mPFS was 6.6-7.5 mo. The most common grade 3 and 4 AEs were thrombocytopenia (15.6%), anemia (10.9%), and fatigue (7.5%). No phase III studies were found. Conclusion: Our study demonstrated that siltuximab combination regimens have shown excellent efficacy in NDMM pts compared to RRMM pts with an ORR of 88% vs. 46%. Similarly, better OS (88% vs. 81%) and mPFS (17 months vs. 8 months) were found in NDMM pts compared to RRMM pts. Neutropenia and thrombocytopenia were the major side effects reported with siltuximab. Pembrolizumab and tabalumab have shown moderate efficacy in RRMM pts with an ORR of 60%. However, isatuximab has shown mild efficacy in RRMM pts with an ORR of 24%. These drugs are well tolerated compared to siltuximab. Significant data in the literature are lacking and data from larger study population are needed. Disclosures No relevant conflicts of interest to declare.

Final Results of a Phase II Study of Sequential R-CHOP and Yttrium-90 Ibritumomab Tiuxetan (RIT) for Elderly High Risk Patients with Untreated Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1793-1793 ◽  
Author(s):  
Paul A. Hamlin ◽  
Maria Alma Rodriguez ◽  
Ariela Noy ◽  
Carol S. Portlock ◽  
David Straus ◽  
...  
Keyword(s):  
High Risk ◽  
Elderly Patients ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Ibritumomab Tiuxetan ◽  
Grade 5 ◽  
Yttrium 90

Abstract Abstract 1793 Introduction: Elderly patients (pts) with high risk DLBCL are one of the fastest growing demographics of pts, but advances over RCHOP21 have not been realized. These pts are often under-represented in clinical trial secondary to comorbidity, ageism, and eligibility requirements. By the age adjusted international prognostic index (aaIPI), pts >60 years (yrs) with high-intermediate (HI) and high (H) risk disease had 5 yr survival (OS) rates of 37% and 21%. Even in the RCHOP era, high risk elderly patients have event-free-survival of roughly 50%. We report the mature data from a phase II study investigating sequential RCHOP followed by yttrium-90 ibritumomab tiuxetan radioimmunotherapy (RIT) in an effort to improve these results. Methods: Untreated ASCT-ineligible pts >60 yrs, with aaIPI HI and H risk DLBCL were eligible for study. Pts received RCHOP21 × 6 cycles at standard doses with prophylactic GCSF and darbepoetin alfa. Pts with responding (CR/PR) or stable disease post RCHOP received RIT, given 6–9 weeks post chemotherapy at 0.4 mCi/kg for platelets (plt) ≥150K and 0.3 mCi/kg for plt 100–149K. Weekly CBCs were performed for 12–13 weeks or until count resolution. Rituximab levels were assessed pre-RIT in a subset of pts. Primary end-points were PFS and OS, with intent-to-treat (ITT) analysis performed for all patients. Statistics anticipated 2/3 of pts (n=43) receiving RIT, with power to demonstrate a 20% improvement in PFS/OS at 2 yrs. Results: 65 pts were consented, with 2 pts having progression prior to a single cycle on protocol, leaving 63 evaluable pts. The median age was 75 (62-86), median KPS 70% (50-100%), Stage III/IV 23/74%, LDH>ULN 91%, ENS>1=45%, BM positive=11%; aaIPI HI/H 45%/55%. Moderate or greater comorbidity was present in 86% of pts (n=65) by NIA/NCI scale. 86% of pts completed RCHOP, with overall response rate (ORR) of 83% (CR/Cru 75%, PR 8%) (Cheson 1999). Fifty pts by ITT were eligible for RIT following RCHOP chemotherapy, with 44 pts ultimately treated. Reasons for discrepancy included low bone marrow cellularity (2pt), AFIB/CHF post day 0 (1 pt), abnormal baseline FISH/cytogenetics (2 pts), withdrawal of consent (1pt). Rituximab levels in 30 pts are available pre-RIT: mean 112 mcg/ml (range 41–196) and did not correlate with outcome. The RIT dose was 0.4 mCi/kg in 38 patients and 0.3 mCi/kg in 6 patients. No patient had altered biodistribution on imaging. RIT was generally well tolerated with expected hematologic nadirs at weeks 6–7. Grade 3/4 non-heme toxicity during RIT included neutropenic fever (2), transient EF decline >20% (1), hip fracture (1), anthracycline induced cardiomyopathy (grade 5), suspected CNS bleed (grade 5). Response post RIT (n=44) was CR/CRu 86%, PR 2%. Response improvement (PR->CR or CRu->CR) occurred in 7 pts (16%). Median followup for surviving pts is 42 months, with median OS and PFS not reached (0.5-74.4). KM estimates of OS and PFS at 42 months by ITT: 64% and 62% respectively. OS and PFS at 42 months for RIT treated pts (n=44): 83.5% and 74.5%. There have been only two relapse >12 months after RIT. The aaIPI (HI vs H) predicted outcomes: OS 75% vs. 49% (p=.008), PFS 68% vs. 45% (p=.01). Conclusion: Sequential RCHOP21 × 6 cycles followed by RIT in an elderly, high comorbidity, high risk DLBCL cohort is associated with very encouraging outcomes by ITT and specifically in the RIT treated pts with long term follow-up. Therapy was well tolerated in this age group and given lack of late relapses, one may hypothesize RIT is addressing minimal residual disease typically associated with recurrence. Outcome is very favorable when compared to historical controls. A prospective Phase III study is needed to confirm these results. Disclosures: Hamlin: Genentech: Honoraria, Speakers Bureau; Biogen Idec: Honoraria, Speakers Bureau; Spectrum: Consultancy, Research Funding; CTI: Consultancy, Research Funding. Off Label Use: Y-90 ibritumumab tiuxetan is not approved for use in DLBCL; it is FDA approved for NHL/indolent lymphoma. Rodriguez:CTI: Research Funding. Noy:Spectrum: Consultancy. McLaughlin:Spectrum: Consultancy. Pandit Tasker:CTI: Research Funding; Spectrum: Research Funding. Zelenetz:GSK: Consultancy; CTI: advisory board.

Phase II study of vorinostat (V) in combination with idarubicin and high-dose cytarabine (IA) as front-line therapy in patients (pts) with high-risk myelodyplsatic syndrome (MDS) or acute myeloid leukemia (AML)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7004-7004
Author(s):  
E. Jabbour ◽  
S. Faderl ◽  
F. Ravandi ◽  
M. Konopleva ◽  
S. Verstovsek ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Ex Vivo ◽  
Phase 1 ◽  
High Dose ◽  
Front Line ◽  
Line Therapy ◽  
Grade 3

7004 Background: Standard induction therapy for pts with AML has not changed over the last 2 decades nor has the outcome of these pts. We demonstrated in vitro and ex vivo that the combination of an histone deacetylase inhibitor with anthraycline is synergistic (Blood 2006;108:1174); an effect that could be mediated by activation of DNA damage/repair pathways, and found that such combination is safe in phase 1 trial (Blood 2007;110:1842). We designed a phase II study of V with IA as front-line therapy for MDS/AML. Methods: Pts with untreated int-2/high-risk MDS or AML ages 15–65 with adequate liver and renal functions and PS, and EF ≥ 50% were eligible. Pts with CBF were excluded. Initial dose of V was 500 mg orally TID for 3 days followed on day 4 by IA (I:12 mg/m2/dx3; A:1.5g/m2/dx4 over 24 hrs). After induction and if in CR, pt can receive 5 cycles of consolidation with V at the same dose and IA (I:8 mg/m2/dx2; A:0.75g/m2/dx3 over 24 hours) followed by 1 year of maintenance with V. The study was powered to demonstrate improvement in PFS at 7 months and acceptable toxicity. Prior to formal initiation of the phase II, the study had a “run-in” phase to confirm the safety of the triple combination. Correlative studies include analysis of DNA repair/damage pathways. Results: 22 pts have been registered. 3 pts with relapsed/refractory AML were treated in the run-in phase. No excess toxicity was observed; 2 achieved CR and 1 CRp. Following these, 19 pts were enrolled on the phase 2 portion. 17 pts were evaluable. Median age was 49 years. Median WBC at presentation was 12.75 x 109/L. Cytogenetic analysis were abnormal in 12 (71%), complex in 10 (59%). 8 (47%) had secondary disease. 4 (23%) were Flt-3 positive. No unexpected grade 3/4 toxicities have been observed. The CR rate was 82%. 1 pt acheived a marrow CR and 2 pts died during induction. CR were universally associated with CG response. All Flt-3+ pts achieved a CR. Only 2 pts (14%) have relapsed (4 and 5 months). The median PFS has not been reached. Conclusions: The combination of IA and V is safe and active in AML/MDS. No stopping rule has been met. Results will be compared with those of a parallel IA study at MDACC. Correlative analysis are ongoing. [Table: see text]

Final results of AGITG ATTAX3 study: Randomized phase II study of weekly docetaxel (T), cisplatin, and fluoropyrimidine (F) with or without panitumumab (P) in advanced esophagogastric (OG) cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4081-4081 ◽  
Author(s):  
Niall C. Tebbutt ◽  
Timothy Jay Price ◽  
Katrin Marie Sjoquist ◽  
Anne-Sophie Veillard ◽  
Merryn Hall ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Growth Factor Receptor ◽  
Adverse Outcomes ◽  
Randomized Phase Ii ◽  
Safety Alert ◽  
Common Grade ◽  
Epidermal Growth ◽  
Grade 3 ◽  
Adeno Carcinoma

4081 Background: This randomized phase II study evaluated the efficacy and safety of P, a fully human mAb against the epidermal growth factor receptor combined with T-based chemotherapy in advanced OG cancer. Methods: Eligible pts had histologically confirmed metastatic OG cancer (adeno-carcinoma and squamous cell carcinoma) were ≥18 years of age, PS 0-2, with adequate renal, haematologic and liver function with measurable disease. All pts provided informed consent. Selection was not based on kras determination. Pts received T 30mg/m2 d1,8, C 60mg/m2 d1 and F; investigator choice of 5FU infusion 160mg/m2/d or capecitabine 500mg/m2bd continuous ±P 9 mg/kg d1 q3w. Treatment was administered for 8 cycles or until PD. The primary endpoint was response rate according to RECIST (1.1) assessed q6w. Planned enrolment target was 100 pts. Stratification variables included histology, PS and choice of F. Results: From April 2010 to November 2011, 77 pts were enrolled from 15 institutions. A safety alert from the REAL3 study (also involving P in OG cancer) prompted an unplanned review of data from ATTAX3 by the IDMC. The IDMC found no evidence of adverse outcomes associated with P, but as it did not appear that P would significantly improve efficacy, they recommended cessation of the study to new enrolment. Previously enrolled pts were treated and followed according to protocol. Median follow up is 24m. Treatment arms were well balanced; median age 59, 64y, male 77%, 87%, PS0-1 95%,90%, adenocarcinoma 90%,90%, capecitabine 67%, 66% for TCF/TCF-P, respectively. Common grade 3/4 toxicities include infection 18%,24%, febrile neutropenia 10%, 5%, anorexia 10%, 24%, nausea 18%,30%, stomatitis 3%,5%, diarrhoea 15%,24% , acneiform rash 0%, 8%, fatigue 18%, 30%, hypomagnesemia 10%, 16% for TCF/TCF-P. Efficacy outcomes are summarized in Table. Conclusions: The addition of P to T-based chemotherapy in advanced OG cancer did not improve efficacy and was associated with an increase in some toxicities. Clinical trial information: ACTRN12609000109202. [Table: see text]

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