A Phase II Trial of FM (Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Indolent Non-Follicular Lymphoma Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2478-2478
Author(s):  
Pier Luigi Zinzani ◽  
Monica Tani ◽  
Stefano Fanti ◽  
Gerardo Musuraca ◽  
Alessio Perrotti ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Safety Data ◽  
Stage Iv ◽  
Stage Iii ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Common Grade ◽  
Grade 3

Abstract We conducted a prospective, single-arm, open-label, non-randomized, multicenter, phase II to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a novel new approach combining induction chemotherapy with Fludarabine and Mitoxantrone (FM) followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated indolent non-follicular lymphoma (indolent non-FL). Patient eligibility was represented by: patients age 18 years or older with biopsy-proven, untreated, bidimensionally measurable stage II, stage III, or stage IV indolent non-FL expressing the CD20 antigen; WHO performance status of 0 to 2. All patients were notified of the investigational nature of this study and signed a written informed consent approved in accordance with institutional guidelines, including the Declaration of Helsinki. The study was approved by the institutional review boards. Patients were treated with standard FM chemotherapy every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM chemotherapy. Patients achieving at least a partial response after 6 cycles of FM chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was greater than 1500/μL, the platelet count exceeded 100.000/μL, and the bone marrow examination at the completion of FM chemotherapy demonstrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). At data reporting for this abstract, 29 patients were enrolled and 26 were evaluable for response. Of these 26 patients, all are evaluable for induction chemotherapy FM regimen and 17 of them also are evaluable after 90Y Ibritumomab Tiuxetan treatment. Histologically, 11 had marginal zone lymphoma, 10 had lymphoplasmacytic lymphoma, and 5 had small lymphocytic lymphoma; 10 were male and 16 female; the median age was 61 years (range 45–82); 4 were stage III, and 21 stage IV. After the FM treatment the overall response rate was 81%, including 50% CR and 31% PR. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 13 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 17 evaluable patients subsequentially treated with 90Y Ibritumomab Tiuxetan, 2/4 (50%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 15 patients; the most common grade ≥ 3 AEs were neutropenia (10 patients) and thrombocytopenia (15 patients). Transfusions of red cells and/or platelets were given to 6 patients. These preliminary data indicate the feasibility, tolerability, and efficacy of the FM plus 90Y Ibritumomab Tiuxetan regimen for patients with untreated indolent non-FL. Final efficacy and safety data will be presented.

A Phase II Trial of FM (Oral Fludarabine and Mitoxantrone) Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Follicular Lymphoma (FL) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2479-2479 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Alessandro Pulsoni ◽  
Manuela Balocco ◽  
Monica Tani ◽  
Stefano Fanti ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Safety Data ◽  
Stage Iv ◽  
Bone Marrow Examination ◽  
Stage Ii ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Open Label ◽  
Grade 3

Abstract We conducted a prospective, multicenter, single-arm, open-label, non-randomized, phase II study to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a new approach combining induction chemotherapy with oral Fludarabine and Mitoxantrone (FM) followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated FL. Patient eligibility was represented by: age ≥ 18 years with biopsy-proven, untreated; stage II – IV FL grade I–II; WHO performance status of 0 to 2. All patients signed a written informed consent. Patients were treated with standard FM chemotherapy (Fludarabine was administered orally at the dose 40 mg/m2/day for 3 consecutive days) every 28 days for 6 cycles. Patients were restaged 4 to 8 weeks after completion of the sixth cycle of FM. Patients achieving at least a PR after 6 cycles of FM chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was > 1500/μL, the platelet count >100.000/μL, lymphocytes expressing the CD20 antigen and the bone marrow examination at the completion of FM demonstrated < 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). At data reporting for this abstract, 62 patients were enrolled and 41 were evaluable for response. Of these 41 patients, all are evaluable for induction FM regimen and 19 of them also are evaluable after 90Y Ibritumomab Tiuxetan treatment. 15 were male and 26 female; the median age was 52.5 years (range 36–70); 5 were stage II, 12 stage III, and 24 stage IV. After the FM treatment the OR rate was 100%, including 73% complete remissions (CR + CRu) and 27% PR. Time to event analyses, including TTP and duration of response are pending further follow-up. Treatment was well tolerated; grade ≥ 3 AEs were seen in 20 patients; the most common grade ≥ 3 AEs was neutropenia. Among the actual 19 evaluable patients subsequentially treated with 90Y Ibritumomab Tiuxetan, 3/5 (60%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 12 patients. These preliminary data indicate: 1) FM regimen including oral fludarabine presents the same activity of i.v. formulation one without significant gastrointestinal toxicity and with a better patient compliance; 2) feasibility, tolerability, and efficacy of the FM plus 90Y Ibritumomab Tiuxetan regimen for untreated FL. Final efficacy and safety data will be presented.

Stage III non small lung cancer (NSCLC): Docetaxel (D), gemcitabine (G), and cisplatin (C) as induction chemotherapy, an Italian phase I study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18201-18201
Author(s):  
S. De Santis ◽  
V. Donato ◽  
M. R. Migliorino ◽  
B. Tedesco ◽  
S. Condo ◽  
...  
Keyword(s):  
Phase I ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase I Study ◽  
Objective Response ◽  
Stage Iii ◽  
Stage Iiia ◽  
Phase Ii Studies ◽  
Stage Iii Nsclc ◽  
Grade 3

18201 Background: Based on the several clinical trials, combined modality therapy became the standard of care for patients with stage III NSCLC “unresectable” with good performance status (Kathy S. Albain, Educational Book ASCO 2006, 453–461; Thomas E. Stinchcombe, Oncologist 2006, 11, 809–823). The most effective induction chemotherapy has yet to be determined. The objective of this prospective phase I study was to define the maximum tolerated dose (MTD), and to evaluate the activity and safety of one of the third generation triplets as a full dose neoadjuvant regimen in patients (pts) with unresectable Stage III NSCLC. Methods: In this study, chemotherapy-naïve pts with stage IIIA-N2 bulky and IIIB (except malignant pleural effusion) NSCLC were eligible. Inclusion into the trial and treatment decisions were done by multidisciplinary panel involving surgeons, medical oncologists and radiotherapists. All drugs were given intravenously on days 1 and 8, and repeated every 3 weeks up to 2 cycles followed by concurrent chemoradiation. D (30–35 mg/m2) was given first, followed by C (35 mg/m2) and G (1000 mg/m2). Results: From Jan ‘06 to Jul ‘06 twelve eligible pts were enrolled, 10/2 m/f gender; median age 63 (50–72), 1 patient with ECOG PS 0, 11 pts with PS 1; 5 pts with stage IIIA-N2 bulky, 7 pts with stage IIIB NSCLC; nine pts were smokers. All pts were evaluable for toxicity. Toxicity grade 3–4 by CTC criteria was: grade 3 neutropenia in 2/3 patients and grade 3 thrombocytopenia in 1/3 patients on the second dose level of chemotherapy (i.e. docetaxel 35 mg/m2), and was considered dose-limiting. Of 9 pts treated at the MTD (i.e. docetaxel 30 mg/m2), only 1 patient developed grade 4 neutropenia and 1 patient grade 3 thrombocytopenia; 3 patients (30%) had grade 2 neutropenia and grade 2 stomatitis. Of 12 evaluable pts for response, after induction chemotherapy eighty-three percent of patients (9/12 pts) had an objective response and 16,6% (2/9 pts) stable disease. Phase II is continuing for larger patient accrual. Conclusions: The recommended doses for further phase II studies are D (30 mg/m2) followed by C (35 mg/m2) and G (1000 mg/m2) every 3 weeks. This regimen is well tolerated and effective, and appears to be an excellent choice for stage III NSCLC. No significant financial relationships to disclose.

Daratumumab, bortezomib and dexamethasone (DVd) vs bortezomib and dexamethasone (Vd) in relapsed or refractory multiple myeloma (RRMM): Efficacy and safety update (CASTOR).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 8036-8036 ◽  
Author(s):  
Suzanne Lentzsch ◽  
Katja C. Weisel ◽  
Maria-Victoria Mateos ◽  
Vania Hungria ◽  
Markus Munder ◽  
...  
Keyword(s):  
Residual Disease ◽  
Randomized Study ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Depth Of Response ◽  
Common Grade ◽  
Previously Treated ◽  
Grade 3 ◽  
Line Of Therapy

8036 Background: Daratumumab (D), a human, CD38-targeting mAb, is well tolerated and induces deep and durable responses in patients (pts) with RRMM. We provide an update of CASTOR (NCT02136134), a multicenter, phase 3, randomized study of DVd vs Vd in RRMM. Methods: All pts received ≥1 prior line of therapy (LOT) and were administered 8 cycles (Q3W) of Vd (1.3 mg/m2 SC bortezomib on days 1, 4, 8, and 11; 20 mg PO/IV dexamethasone on days 1-2, 4-5, 8-9, and 11-12) ± D (16 mg/kg IV once weekly in Cycles 1-3, every 3 weeks for Cycles 4-8, then every 4 weeks until progression). Bortezomib-refractory pts were ineligible. Minimal residual disease (MRD) was assessed upon suspected CR and at 6 and 12 months following the first dose at sensitivities of 10–4, 10–5, and 10–6using the ClonoSEQ assay (Adaptive Biotechnologies, Seattle, WA). Results: Pts received a median (range) of 2 (1-10) prior LOTs. 66% were previously treated with bortezomib and 21% were refractory to lenalidomide in their last prior LOT. After a median follow-up of 13.0 months, PFS was significantly prolonged with DVd vs Vd (median: not reached vs 7.1 months; HR, 0.33; 95% CI, 0.26-0.43; P< 0.0001). This PFS benefit was seen regardless of number of prior LOTs received, with greatest benefit observed in 1 prior line pts (median: not reached vs 7.9 months; HR, 0.22; 95% CI, 0.14-0.34; P< 0.0001). ORR was also significantly higher for DVd vs Vd (84% vs 63%), along with ≥VGPR (62% vs 29%) and ≥CR (26% vs 10%; P< 0.0001 for all). MRD-negative rates were ≥4-fold higher at all three sensitivity thresholds with DVd vs Vd (10% vs 2% at 10–5 threshold). Pts who achieved MRD negativity demonstrated prolonged PFS compared with MRD-positive pts. 37 (15%) and 58 (24%) deaths were observed in DVd vs Vd, respectively, and follow up is ongoing. The most common grade 3/4 TEAE was thrombocytopenia (45% vs 33%). Updated efficacy and safety data will be presented. Conclusions: DVd provided significant benefits with respect to PFS, ORR, depth of response, and MRD-negative rate vs Vd. No new safety signals were reported. These data continue to support the use of DVd in RRMM pts and indicate that pts with 1 prior LOT will derive the most benefit. Clinical trial information: NCT02136134.

A phase II trial of thalidomide (T), irinotecan (I) and gemcitabine (G) in chemonaive patients with advanced non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17068-17068
Author(s):  
A. R. Jazieh ◽  
R. Komrokji ◽  
S. Patil ◽  
D. Flora ◽  
M. Knapp ◽  
...  
Keyword(s):  
Phase Ii ◽  
Advanced Nsclc ◽  
Survival Rates ◽  
Stage Iv ◽  
Thromboembolic Events ◽  
Early Withdrawal ◽  
Common Grade ◽  
Grade 3 ◽  
Ecog Ps ◽  
Lost To Follow Up

17068 Background: Chemotherapy with platinum based doublets provides only a modest benefit in advanced NSCLC with a median overall survival (OS) of 8 months and 1-year survival rate of 33% (Schiller JH et al, N Engl J Med 2002). We performed a phase II study to determine the efficacy of thalidomide, an immunomodulatory agent with antiangiogenic activity, in combination with chemotherapy in patients with advanced NSCLC. Methods: Chemonaive patients with stage IIIB/IV NSCLC with ECOG PS≤ 2 and adequate organ function were treated with G (1000 mg/m2) and I (100 mg/m2) IV on days 1 and 8 of a 21 day cycle. Patients also received T (200 mg orally with escalation as tolerated to a maximum of 400 mg daily). Therapeutic anticoagulation with coumadin was given to the last 11 patients. Results: Twenty four patients were enrolled: median age 57 years (41–76); M:F=17:7; ECOG PS 0/1/2=13/7/3; stage IV: IIIB= 21:3 and CNS involvement: 6. Two pts died before treatment, 1 was ineligible and 1 was lost to follow up. The remaining 20 pts received a median of 4 treatment cycles (range 1–6). The regimen was generally well tolerated and the most common grade 3–4 toxicities encountered were: diarrhea (4); pneumonia (3) and thromboembolic events (3). There were no thromboembolic events after anticoagulation was initiated. Two patients (10%) experienced partial response, 14 (70%) experienced stable disease, 1 had progressive disease. Three patients (15%) were not evaluable for response due to early withdrawal. The median OS was 10.8 months (range 0.6–37+) and 1-year and 2-year survival rates were 37% and 16%, respectively. The median time to progression was 3.6 months (range 0.2–11+). Conclusions: The combination of thalidomide and chemotherapy is reasonably well tolerated and active in advanced NSCLC as evidenced by good OS and 1- and 2-year survival rates. The addition of thalidomide to a non-platinum based regimen appears to compare favorably to the results of the traditional platinum based doublets. [Table: see text]

Phase II randomized trial of radiotherapy (RT), cetuximab (E), and pemetrexed (Pem) with or without bevacizumab (B) in locally advanced squamous cell carcinoma of the head and neck (SCCHN).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6043-6043 ◽  
Author(s):  
Athanassios Argiris ◽  
James Ohr ◽  
Greg J. Kubicek ◽  
Uma Duvvuri ◽  
Dwight Earl Heron ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Stage Iii ◽  
Community Practice ◽  
History Of ◽  
Grade 3

6043 Background: We previously developed a novel regimen by the addition of Pem to RT and E (Ann Oncol 2011;22:2482). The current study evaluated PemE in the phase II setting and assessed the addition of B, an anti-VEGF monoclonal antibody, to PemE based on promising data with Pem/B (JCO 2011;29:1140) and E/B (Ann Oncol 2013;24:200) in recurrent/metastatic SCCHN. Methods: Patients (pts) with previously untreated stage III/IV SCCHN of the oropharynx, larynx or hypopharynx, performance status (PS) 0-1, no history of bleeding, and adequate laboratory parameters were randomized after stratification for PS, stage and site to: RT 2 Gy/day to 70Gy, E 250mg/m2 weekly, after a loading dose of 400 mg/m2 1 week prior starting RT, and Pem 500mg/m2 every 21 days x 3 cycles (arm A, PemE), or the same regimen plus B 15mg/kg every 21 days x 3 cycles during RT followed by B maintenance x 8 cycles (arm B, B-PemE), with antibiotic prophylaxis. The primary endpoint was progression-free survival (PFS) with a target of 64% at 2 years; planned sample size was 80. Results: 79 pts were randomized of whom 77 were eligible and analyzable (arm A/B:36/41); oropharynx 65/larynx 12; HPV+ 38/HPV- 15/HPV unknown 24; stage IV 54/stage III 23. 31 pts were enrolled in community centers. Treatment delivery of E and Pem was similar between arms: E, median number of doses 8 (range, 5-11); Pem 3 (2-3); and B 3 (1-3). 5 deaths occurred: 3 due to progression; 1 from unknown cause; 1 pt died from hemoptysis after bronchoscopy within 4 weeks of the 8th cycle of B leading to elimination of B maintenance after the 6th pt was enrolled. 9 pts (2 HPV+) progressed. With a median follow-up of 18 months, the 2-year PFS was 81% vs 87% and the 2-year overall survival (OS) was 96% vs 86% for arm A vs B. Grade 3/4 acute toxicities for arm A vs B (N=59) : dermatitis 3/1 vs 4/1; mucositis 13/2 vs 13/0; neutropenia 7/4 vs 7/3; rash 6/1 vs 8/1; fatigue 1/0 vs 3/0; weight loss 2/0 vs 5/0. Conclusions: Both regimens are feasible in academic and community practice settings with expected toxicities. Preliminary efficacy results are very promising and better than projected, however, the addition of B does not appear to improve outcomes. Clinical trial information: NCT00703976.

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.

Efficacy and Safety of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) Therapy with Rituximab Maintenance in Patients with Untreated Low-Grade Follicular Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2633-2633 ◽  
Author(s):  
John William Sweetenham ◽  
Karel Dicke ◽  
John Arcaroli ◽  
Karen Kogel ◽  
Tahir M. Rana ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
International Workshop ◽  
Stage Iv ◽  
Small Population ◽  
Low Grade ◽  
Efficacy And Safety ◽  
Ibritumomab Tiuxetan ◽  
Eligibility Criteria ◽  
Rituximab Maintenance ◽  
Imaging Dose

Abstract Background: Recent trials have demonstrated the efficacy of rituximab induction therapy, when followed by maintenance rituximab, in patients with untreated low-grade follicular NHL. Earlier studies, employing low-dose total-body irradiation as an initial treatment for follicular lymphoma (FL), have previously shown the inherent radiosensitivity of the disease. Based on these findings, we evaluated the efficacy and safety profile of frontline 90Y ibritumomab tiuxetan (Zevalin®) delivered prior to maintenance rituximab in patients with low-grade FL. Methods: Patients were eligible for treatment if they presented with histologically confirmed, previously untreated low-grade FL. Additional eligibility criteria included stage III or IV disease and a need for therapeutic intervention because of constitutional symptoms, evidence of disease progression, or organ dysfunction directly attributable to NHL. Patients were excluded if there was evidence of histologic transformation to aggressive disease. On day 1, patients received an initial infusion of rituximab (250 mg/m2) followed by an imaging dose of Indium 111 (111In) ibritumomab tiuxetan (5 mCi). One week later, a second infusion of rituximab (250 mg/m2) was given, proceeded by an injection of 90Y ibritumomab tiuxetan (0.3 or 0.4 mCi/kg, depending upon platelet count). Rituximab maintenance therapy (375 mg/m2 x 4) was scheduled at 6-month intervals over 2 years. Endpoints included clinical response rates using standard International Workshop Response Criteria (IWRC) and toxicity. Results: Ten patients, presenting with grade I or II FL, have been treated with 90Y ibritumomab tiuxetan, and 8 are evaluable for treatment response. The median age of patients was 58 years (range, 40–82) and 50% (5/10) of patients had stage IV disease. Delivered doses of 90Y ibritumomab tiuxetan ranged from 21–32 mCi. Toxicities were primarily hematologic with grade 3 cytopenia occurring in 38% (3/8) of patients. Of the 8 patients qualifying for evaluation, 5 (62%) had complete responses and 3 (38%) had partial responses to 90Y ibritumomab tiuxetan induction. Conclusions: These data illustrate that frontline 90Y ibritumomab tiuxetan therapy produces high rates of response (100% in this small population) in patients with low-grade FL. Toxicities following administration of radiolabeled antibody were manageable. Further follow-up is needed to determine the long-term efficacy of combining frontline radioimmunotherapy with antibody-based maintenance.

A Phase II Trial of CHOP Chemotherapy Followed by Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) for Previously Untreated Elderly Diffuse Large B-Cell Lymphoma (DLBCL) Patients.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2431-2431 ◽  
Author(s):  
Pier Luigi Zinzani ◽  
Monica Tani ◽  
Stefano Fanti ◽  
Vittorio Stefoni ◽  
Gerardo Musuraca ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Chop Chemotherapy ◽  
Ibritumomab Tiuxetan ◽  
Large B Cell Lymphoma ◽  
Common Grade ◽  
Grade 3 ◽  
Large B Cell

Abstract In the last 20 years, the major improvement over the use of CHOP has been the addition of anti-CD20 immunotherapy (Rituximab). This advancement was first demonstrated in a randomized trial in elderly patients with diffuse large B-cell lymphoma (DLBCL). Single-agent radioimmunotherapy activity, in particular Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®), has been demonstrated in heavily pretreated DLBCL patients. Recently, the preliminary data of a phase II trial have showed that 90Y Ibritumomab Tiuxetan have useful activity in the treatment of relapsed/refractory elderly DLBCL (Morschhauser et al, Blood 2004, 104: 41a), with no unexpected toxicities observed. The results of this study support a further evaluation of 90Y Ibritumomab Tiuxetan in combination with chemotherapy earlier in the time course of elderly DLBCL. We conducted a prospective, single-arm, open-label, non-randomized, phase II to evaluate the efficacy and safety of 90Y Ibritumomab Tiuxetan of a novel new approach combining induction chemotherapy with CHOP followed by consolidation with 90Y Ibritumomab Tiuxetan for patients with previously untreated elderly DLBCL. Patient eligibility was represented by: patients older than 60 years with biopsy-proven, untreated, bidimensionally measurable stage II, stage III, or stage IV DLBCL expressing the CD20 antigen; WHO performance status of 0 to 2. All patients signed a written informed consent approved in accordance with institutional guidelines. The study was approved by the institutional review board. Patients were treated with standard CHOP chemotherapy every 21 days for 6 cycles. Patients were restaged 4 to 6 weeks after completion of the sixth cycle of CHOP chemotherapy. Patients achieving at least a partial response after 6 cycles of CHOP chemotherapy were eligible for consolidation with 90Y Ibritumomab Tiuxetan provided the granulocyte count was greater than 1500/μL, the platelet count exceeded 100.000/μL, and the bone marrow examination at the completion of CHOP chemotherapy demonstrated no more than 25% involvement with lymphoma. All patients were to receive a single dose of 90Y Ibritumomab Tiuxetan 14.8 MBq/kg (0.4 mCi/kg) up to a maximum dose of 1184 MBq (32 mCi). A total of 20 patients have been enrolled: 12 were male and 8 female; the median age was 68 years (range 61–84); 6 were stage II, 14 stage III-IV. After the CHOP treatment the overall response rate was 100%, including 15 (75%) CR and 5 (25%) PR. Treatment was well tolerated; grade ≥ 3 AEs were seen in 13 patients; the most common grade ≥ 3 AEs was neutropenia. After the treatment of all 20 patients with 90Y Ibritumomab Tiuxetan, 4/5 (80%) patients improved their remission status from PR to CR. The 90Y Ibritumomab Tiuxetan toxicity included grade ≥ 3 hematologic AEs in 11/20 patients; the most common grade ≥ 3 AEs were neutropenia (11 patients) and thrombocytopenia (7 patients). Transfusions of red cells and/or platelets were given to 2 patients. Time to event analyses, including TTP and duration of response are pending further follow-up. These preliminary data indicate the feasibility, tolerability, and efficacy of the CHOP plus 90Y Ibritumomab Tiuxetan regimen for patients with untreated elderly DLBCL.

Encouraging results from a phase I study of capecitabine (X), irinotecan (I) and oxaliplatin (O) as first-line therapy in patients (pts) with metastatic colorectal cancer (MCRC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4086-4086 ◽  
Author(s):  
J. Maroun ◽  
D. Jonker ◽  
C. Cripps ◽  
R. Goel ◽  
D. Lister ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Dose Level ◽  
Phase Ii ◽  
Dose Escalation ◽  
Line Treatment ◽  
Efficacy And Safety ◽  
First Line ◽  
Common Grade ◽  
Grade 3 ◽  
First Line Treatment

4086 Background: First-line treatment with I, O and infusional 5-FU/Leucovorin (LV) triplets is associated with high response rates and long survival in MCRC. The oral fluoropyrimidine X is better tolerated and shows improved response rates vs. 5- FU/LV in MCRC. This dose-escalation study aims to establish dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of I, O and X and to evaluate efficacy and safety in first-line. Methods: Starting doses were: I (180mg/m2 i.v. d1), O (85mg/m2 i.v. d1), × (850mg/m2 bid orally d2–15). Dose escalations are based on toxicity observed at previous dose level (DL), until DLT, MTD and RPIID are reached. Results: We have enrolled 27 pts (21 men, 6 women), median age 59 years (range 25–74), at 6 DLs. ECOG PS was 0 or 1 in 25 pts, and 2 in 2 pts. Pts received a median of 10 cycles (range 1–23). All pts are evaluable for toxicity (24 for efficacy). Most common grade 3/4 hematological adverse events (AEs) during dose escalation: granulocytopenia (41%), anemia (7%), and thrombocytopenia (15%). Most common grade 3 non-hematological AEs: late-onset diarrhea (11%), fever (14%), and fatigue (4%). DLTs at each dose level: DL1 (1 febrile neutropenia with bowel perforation); DL2 (1 grade 3 diarrhea); DL3 (1 febrile neutropenia with grade 2 edema); DL4 (1 severe febrile neutropenia in cycles 2&3, pt deceased due to sepsis); no DLTs were reported at DL5 & 6. MTD has not yet been reached. Overall response rate is 79% (95% CI, 62–97%), including 2 CRs and 17 PRs (3 still unconfirmed). Disease control rate is 92%. Two pts had subsequent curative liver resection and 4 pts are under consideration for curative procedures. Median progression-free survival is 15 months (95% CI, 8–22). Conclusions: XIO is well tolerated and highly effective as first-line treatment for MCRC. Severe neutropenia was significant but of short duration and manageable; it is likely to be the main DLT. MTD has not yet been identified but is expected shortly. A phase II study to confirm the efficacy and safety of XIO, possibly in combination with targeted agents, will follow. Supported by Roche, Sanofi-Aventis, and Pfizer Canada. No significant financial relationships to disclose.

The anti–PD-1 antibody spartalizumab (S) in combination with dabrafenib (D) and trametinib (T) in previously untreated patients (pts) with advanced BRAF V600–mutant melanoma: Updated efficacy and safety from parts 1 and 2 of COMBI-i.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9531-9531 ◽  
Author(s):  
Georgina V. Long ◽  
Celeste Lebbe ◽  
Victoria Atkinson ◽  
Mario Mandalà ◽  
Paul D. Nathan ◽  
...  
Keyword(s):  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Safety Data ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Antigen Expression ◽  
Synergistic Activity ◽  
Efficacy And Safety ◽  
Grade 3

9531 Background: Checkpoint inhibitors and targeted therapies have improved outcomes in pts with BRAF V600–mutant advanced melanoma; however, many pts progress and new treatment (tx) strategies are needed. BRAF inhibition increases T-cell infiltration, melanoma antigen expression, and PD-1/PD-L1 expression, which may lead to synergistic activity with anti–PD-1 therapy. Methods: COMBI-i is investigating first-line S 400 mg Q4W + D 150 mg BID + T 2 mg QD in pts with unresectable or metastatic BRAF V600–mutant melanoma (NCT02967692). Here we report pooled efficacy and safety data from parts 1 (run-in cohort) and 2 (biomarker cohort). Response was assessed per RECIST v1.1. Results: 36 pts were enrolled (part 1: n = 9; part 2: n = 27); 18 (50%) had stage IV M1c and 15 (42%) had elevated LDH levels. At the data cutoff (median follow-up, 15.2 mo), tx was ongoing in 17 pts (47%). The confirmed objective response rate (ORR) by investigator assessment was 75% (n = 27), with 33% complete responses (CRs; n = 12). Medians for duration of response (DOR; 7/27 pts with events), progression-free survival (PFS; 13/36 pts with events), and overall survival (OS; 7/36 pts with events) were not reached. 12-mo DOR rate was 71.4% (95% CI, 49%-85%). 12-mo PFS and OS rates were 65.3% (95% CI, 47%-79%) and 85.9% (95% CI, 69%-94%), respectively. In pts with high baseline LDH: ORR was 67%, with 3 CRs (20%), median PFS was 10.7 mo (events in 10/15 pts [67%]), and median OS was not reached, with events in 6/15 pts (40%). All pts had ≥ 1 AE; 27 (75%) had grade ≥ 3 AEs. 6 pts (17%) had AEs leading to discontinuation of all 3 study drugs. Any-grade AEs in ≥ 40% of pts included pyrexia, chills, fatigue, cough, and arthralgia. Grade ≥ 3 AEs in > 3 pts were neutropenia, pyrexia, and increased lipase. One pt died of cardiac arrest that was not considered related to study tx. Conclusions: S+D+T showed promising and durable ORR (75%) with CR in 33% of pts. With > 15 mo of follow-up, median PFS was not reached. The safety profile was manageable reflecting individual toxicities of D, T, and S. The global, placebo-controlled, randomized phase 3 (part 3) of COMBI-i is ongoing. Clinical trial information: NCT02967692.

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