Rituximab in Combination With Fludarabine Chemotherapy in Low-Grade or Follicular Lymphoma

2005 ◽  
Vol 23 (4) ◽  
pp. 694-704 ◽  
Author(s):  
M.S. Czuczman ◽  
A. Koryzna ◽  
A. Mohr ◽  
C. Stewart ◽  
K. Donohue ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Infectious Complications ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Similar Response ◽  
Open Label ◽  
Treatment Naïve

Purpose To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naïve or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. Patients and Methods This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. Results An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naïve and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. Conclusion Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

scholarly journals Safety and activity of pembrolizumab in combination with rituximab in relapsed or refractory follicular lymphoma

2022 ◽  
Author(s):  
Loretta J. Nastoupil ◽  
Collin K Chin ◽  
Jason R Westin ◽  
Nathan H Fowler ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Follicular Lymphoma ◽  
Liver Enzyme ◽  
Response Rate ◽  
Progression Free Survival ◽  
Complete Response ◽  
Low Grade ◽  
Phase 2 ◽  
Open Label ◽  
Grade 3

PD-1 blockade enhances the function of anti-tumor T-cells and antibody-dependent cell-mediated cytotoxicity (ADCC) of NK cells. In a single-center, open-label, phase 2 trial, we tested the combination of pembrolizumab, an anti-PD-1 monoclonal antibody and rituximab, an anti-CD20 monoclonal antibody that induces ADCC, in 30 follicular lymphoma (FL) patients with rituximab-sensitive disease who relapsed after ≥1 prior therapy. Pembrolizumab was administered at 200mg IV every 3 weeks for up to 16 cycles and rituximab was given at 375mg/m2 IV weekly for 4 weeks in cycle 1 only. The most common grade 3/4 adverse events (AE) were liver enzyme abnormalities (3%), diarrhea (3%), nausea (3%), aseptic meningitis (3%) and pancreatitis (3%). Low-grade immune-related AEs were reported for 80% of patients, including diarrhea (43%), liver enzyme abnormalities (33%), thyroid dysfunction (27%), and rash (23%). Grade 3 or 4 immune related AEs occurred in 13% of patients. Treatment-related AEs led to discontinuation in 6 (20%) patients. Overall response rate (primary endpoint) was 67% and complete response rate was 50%. Median progression-free survival (PFS) was 12.6 months (95% CI, 8.2-27.6 months), the 3-year overall survival rate was 97%, and 23% of patients were in remission at a median follow up of 35 months. Presence of a high CD8+ T-effector score at baseline in the tumor was associated with induction of a complete response and improved PFS. In this single arm, phase 2 study, the combination of pembrolizumab and rituximab demonstrates favorable efficacy and safety profile in relapsed FL. This trial is registered at www.clinicaltrials.gov: NCT02446457.

Bortezomib Added to R-CVP Is Safe and Effective for Previously Untreated Advanced-Stage Follicular Lymphoma: A Phase II Study by the National Cancer Institute of Canada Clinical Trials Group

2011 ◽  
Vol 29 (25) ◽  
pp. 3396-3401 ◽  
Author(s):  
Laurie H. Sehn ◽  
David MacDonald ◽  
Sheldon Rubin ◽  
Guy Cantin ◽  
Morel Rubinger ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Phase Ii ◽  
Response Rate ◽  
Complete Response Rate ◽  
Standard Dose ◽  
Complete Response ◽  
Phase Iii ◽  
High Risk Population ◽  
Advanced Stage ◽  
Grade 3

Purpose Bortezomib has demonstrated promising activity in patients with follicular lymphoma (FL). This is the first study to evaluate the safety and efficacy of bortezomib added to rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) in previously untreated advanced-stage FL. Patients and Methods This is a phase II multicenter trial adding bortezomib (1.3 mg/m2 days 1 and 8) to standard-dose R-CVP (BR-CVP) for up to eight cycles in patients with newly diagnosed stage III/IV FL requiring therapy. Two co-primary end points, complete response rate (complete response [CR]/CR unconfirmed [CRu]) and incidence of grade 3 or 4 neurotoxicity, were assessed. Results Between December 2006 and March 2009, 94 patients were treated with BR-CVP. Median patient age was 57 years (range, 29 to 84 years), and the majority had a high (47%) or intermediate (43%) Follicular Lymphoma International Prognostic Index score. BR-CVP was extremely well tolerated, with 90% of patients completing the intended eight cycles. No patients developed grade 4 neurotoxicity, and only five of 94 patients (5%; 95% CI, 0.8% to 9.9%) developed grade 3 neurotoxicity, which was largely reversible. On the basis of an intention-to-treat analysis, 46 of 94 patients (49%; 95% CI, 38.8% to 59.0%) achieved a CR/CRu, and 32 of 94 patients (34%) achieved a partial response, for an overall response rate of 83% (95% CI, 75.4% to 90.6%). Conclusion The addition of bortezomib to standard-dose R-CVP for advanced-stage FL is feasible and well tolerated with minimal additional toxicity. The complete response rate in this high-risk population compares favorably to historical results of patients receiving R-CVP. Given these results, a phase III trial comparing BR-CVP with R-CVP is planned.

Optimal combination therapy with tropisetron in 445 patients with incomplete control of chemotherapy-induced nausea and vomiting.

1994 ◽  
Vol 12 (11) ◽  
pp. 2439-2446 ◽  
Author(s):  
F Hulstaert ◽  
S Van Belle ◽  
H Bleiberg ◽  
J L Canon ◽  
M Dewitte ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Moderate Increase ◽  
Open Label ◽  
Double Blind ◽  
Once Daily ◽  
Antiemetic Agent ◽  
To Receive

PURPOSE This study evaluated tropisetron (Navoban; Sandoz Pharma, Basle, Switzerland)-based combination therapy in patients who had incomplete control of chemotherapy-induced nausea or vomiting when using tropisetron as a single antiemetic agent. PATIENTS AND METHODS One thousand seventy-two patients, who were scheduled to receive at least two identical cycles of emetogenic chemotherapy, were treated with 5 mg tropisetron once daily in their first chemotherapy course. A 2 x 2 x 2 factorial design was used to evaluate three additional treatments to the recommended 5 mg once daily (intravenously [i.v.] on day 1; orally on days 2 through 6) tropisetron regimen during course 2 in those patients who had shown incomplete control of nausea and/or vomiting on any day of course 1. Four hundred forty-five patients were centrally randomized to receive, in addition, open-label dexamethasone (day 1, 0.2 mg/kg i.v.; days 2 through 6, 8 mg orally) and/or open-label alizapride (day 1, 100 mg i.v. and 4 x 50 mg orally; days 2 through 6, 4 x 50 mg orally) and/or double-blind tropisetron (ie, doubling the dose to 10 mg once daily) or corresponding placebo. RESULTS Complete response rates (no nausea and no vomiting) were 72% for day 1 and 48% for days 1 through 6 of course 1. During course 2, more complete responders were observed when dexamethasone was added, both for day 1 (76% v 66%, P = .020) and for days 1 through 6 (50% v 34%, P = .0004). A moderate increase in the complete response rate was seen with the addition of conventional-dose alizapride (day 1, 75% v 68%, P = .14; days 1 through 6: 47% v 37%, P = .041). Doubling the dose of tropisetron did not change the complete response rate. CONCLUSION The addition of dexamethasone significantly increases the complete response rate of both acute and delayed emesis in patients who have incomplete disease control with tropisetron alone.

Results of Induction Chemotherapy in Children Older Than 1 Year With a Stage 4 Neuroblastoma Treated With the NB 97 French Society of Pediatric Oncology (SFOP) Protocol

2005 ◽  
Vol 23 (3) ◽  
pp. 532-540 ◽  
Author(s):  
Dominique Valteau-Couanet ◽  
Jean Michon ◽  
Andrée Boneu ◽  
Chantal Rodary ◽  
Yves Perel ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Response Rate ◽  
Complete Response Rate ◽  
Staging System ◽  
Complete Response ◽  
Institutional Setting ◽  
Hematologic Toxicity ◽  
Complete Regression ◽  
French Society ◽  
Stage 4

Purpose To test the metastatic response rate in stage 4 neuroblastoma, using dose-intensive induction chemotherapy in a multi-institutional setting. Patients and Methods From 1998 to 1999, 47 consecutive children were treated according to N7 protocol. Children received cyclophosphamide 140 mg/kg, doxorubicin 75 mg/m2, and vincristine 0.066 mg/kg (CAV) in cycles 1, 2, 4, and 6, and cisplatinum 200 mg/m2 and etoposide 600 mg/m2 (P/VP) in cycles 3, 5, and 7. The International Neuroblastoma Staging system was used with an emphasis on skeletal evaluation by 123-iodine-metaiodobenzylguanidine (MIBG) scintigraphy. A phase II study evaluating the metastasis complete response rate after induction chemotherapy was conducted in patients who had positive metastatic sites on MIBG scans at diagnosis. Results Forty-six patients were assessable for toxicity. Hematologic toxicity was the main toxicity observed. Neutropenia was more frequent after CAV than after P/VP (P < .001). A higher rate of thrombocytopenia was observed after P/VP (P = .03). Forty patients with positive MIBG were assessable for metastatic response, and complete regression of metastases was achieved in 17 patients (ie, 43%; 95% CI, 27% to 59%). Of all 47 patients, 21 achieved complete metastatic response. Conclusion The N7 induction chemotherapy protocol was feasible in a multicentric setting. The observed metastasis complete response rate was similar to that obtained in our previous studies and significantly lower than that published in a previous series using the same regimen. In our hands, escalating doses of cyclophosphamide and prolonging conventional chemotherapy with the same drugs failed to improve the metastasis complete response rate.

Accelerated R-COP:A Pilot Study for the Treatment of Follicular Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4747-4747
Author(s):  
Joseph R. Bertino ◽  
Strair Roger ◽  
Rubin Arnold ◽  
Gharibo Mecide ◽  
Schaar Dale
Keyword(s):  
Pilot Study ◽  
Follicular Lymphoma ◽  
Progressive Disease ◽  
Response Rate ◽  
Complete Response Rate ◽  
Dose Intensity ◽  
Complete Response ◽  
Neutropenic Fever ◽  
Pet Scans ◽  
Density Treatment

Abstract To test the hypothesis that dose intensity/dose density treatment may improve the complete response rate and remission duration in patients with follicular lymphoma (grades I and II, ECOG performance 0–2, Stages III and IV, progressive disease), a combination of known effective agents were administered as follows: rituximab,375 mg/m2; cyclophosphamide, 1000 mg/m2; and vincristine, 2mg (cap), IV every two weeks. Prednisone, 50 mg, was given p.o., every other day for 30 days then tapered over the next 30 days. G- CSF was administered days 7–10 following each treatment. Patients were evaluated for response after 5 and 10 cycles, that included imaging with CT and PET scans. Toxicity was mild to moderate, consisting mainly of paresthesias, requiring attenuation of the vincristine dose in some patients. There were no instances of neutropenic fever requiring hospitalization. In this pilot study, 6 of 7 patients previously untreated achieved a CR, and none have relapsed to date (6+ to 20+ months after completion of treatment). Two heavily treated patients, including relapse from agents used in this regimen, had PRs, lasting 2 and 8+ months. This program is well tolerated with a high CR rate, and may serve as a basis for future trials.

Sandoz rituximab (GP2013; SDZ-RTX) for the treatment of diffuse large B-cell lymphoma (DLBCL): Interim safety results of the non-interventional, observational, multicenter, open-label REFLECT study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19020-e19020 ◽  
Author(s):  
Manfred Welslau ◽  
Norbert Marschner ◽  
Thomas Wolff ◽  
Burkhard Joerg Otremba ◽  
Julian Topaly ◽  
...  
Keyword(s):  
Response Rate ◽  
Early Stage ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Open Label ◽  
Bulky Disease ◽  
Curative Therapy ◽  
Treatment Naïve ◽  
Full Analysis

e19020 Background: SDZ-RTX is approved in Europe for the same indications as reference rituximab, based on the totality of evidence for biosimilarity. REFLECT, a real-world study of SDZ-RTX as curative therapy for treatment-naïve CD20+ DLBCL, represents the first biosimilar rituximab post-approval study in DLBCL. Methods: The study includes patients (pts) aged ≥18 years, eligible for rituximab and cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP). R-CHOP is administered according to product label. The primary endpoint is complete response rate at the end of treatment. Secondary endpoints include overall response rate, progression-free survival at 12 months, and adverse events (AE). Data are collected at baseline and every study visit for 12 months (efficacy) and ≥30 days after last SDZ-RTX dose (safety). No imputation for missing data is planned; endpoints are summarized descriptively. Results: In an interim analysis (cut off: Sep 6, 2018; recruitment approx. 50% complete), the full analysis set comprised 80 pts: 38 males (47.5%) and 42 females (52.5%), with median (min, max) age 68.5 years (23, 91); 70% of pts were aged ≥60 years. In total, 6 pts have discontinued. Most pts had little or no restriction in daily activities; >80% had ECOG score of 0 (34%) or 1 (50%). B-symptoms were reported in 15 pts (19%). Extranodal infiltration was observed in 40 pts (50%) and bulky disease was observed in 9 pts (11.3%). Most pts had early stage (I–IIB: 63.8%), low to intermediate risk disease (IPI Score 0–2: 61.3%). A summary of safety is reported in the Table. AEs were reported in 53 (66%) pts and 19 (24%) pts had serious AEs. Treatment-related AEs were reported in 13 pts (16%). The most frequent AEs were polyneuropathy (n=10, 12.5%), anemia (n=8, 10%), and fatigue (n=8, 10%). Conclusions: Interim baseline data are as expected for treatment-naïve pts with CD20+ DLBCL; safety results are as expected for rituximab-based treatment. The study is ongoing. [Table: see text]

Clinical Efficacy of Lenalidomide {Revlimid®} in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL): Updated Results of a Phase II Clinical Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 306-306 ◽  
Author(s):  
Asher Alban Chanan-Khan ◽  
Kena C. Miller ◽  
Laurie Musial ◽  
Swaminatha Padmanabhan ◽  
David Lawrence ◽  
...  
Keyword(s):  
Phase Ii ◽  
Clinical Efficacy ◽  
Response Rate ◽  
Expression Profiles ◽  
Single Agent ◽  
Tumor Lysis Syndrome ◽  
Complete Response ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Antitumor Effects

Abstract Introduction: Lenalidomide (L) is an immunomodulatory agent (IMiD®), recently approved for treatment of patients (pts) with previously treated multiple myeloma and del 5q- MDS. Its antitumor effects are reported to be mediated at least in part through modulation of both the cytokine and the immune cellular tumor microenvironment. Clinical efficacy of L in pts with B-CLL has not been investigated previously. In a phase II clinical study, we examined the antileukemic effects of L in pts with relapse (rel) or refractory (ref) B-CLL. Patients and Methods: CLL pts with rel or ref disease were eligible. L was given at 25mg PO QD from days 1–21 of 28-day cycle. Response was assessed every month using the NCI-WG 1996 criteria. Treatment with L was continued until progressive disease (PD) or molecular complete response (CR). Pts with PD received rituximab (R) (375mg/m2) with L. Target enrollment was 45 patients. Results: Forty-five pts, median age of 64 years (range: 42–75) were enrolled. Advance stage disease was noted in 64%, elevated B2M in 24% and fludarabine refractory disease in 51% of the pts. Pts had a median of 3 prior therapies (range 1–10). All pts are evaluable for toxicity. Thrombocytopenia and neutropenia were the most common hematologic toxicity while fatigue and flare reaction (sudden, tender enlargement of lymph node, liver and/or spleen, with or without rash, low grade fever and/or increase in white blood counts) were the most common non-hematologic complications. Two patients experience reversible tumor lysis syndrome. On an intent-to-treat analysis, overall response rate was 42% with complete remission in 9% (n=4) and partial remission in 33% (n=15) of the pts. Molecular complete response (determined by PCR) was noted in 3 pts. Twelve pts were inevaluable (unable to complete 2 treatment cycles; either for toxicity or consent withdrawal) 4 are too early for response evaluation. Response rate among evaluable patients was 65.5% (19/29). To date only 2 pts have required the addition of R to L due to PD. Both have achieved a PR with combination therapy. Correlative studies: we evaluated baseline T and NK cell repertoire, modulation of cytokines (VEGF, IL-10, IL-6, TNF-alpha) as well as modulation of gene expression profiles before and after treatment with L, this data will be presented at the meeting. Conclusion: L is clinically active in pts with rel/ref CLL. CR’s, as well as, molecular CR determined by PCR were achieved with single agent L. Interestingly, in pts who developed resistance to L alone, addition of R resulted in a clinical response. These results are exciting and warrant further investigation of L in CLL pts. Final results of this study will be presented at the meeting.

Immune priming with nivolumab followed by nivolumab and rituximab in first-line treatment of follicular lymphoma: The phase 2 1st FLOR study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7560-7560
Author(s):  
Eliza Anne Hawkes ◽  
Sze Ting Lee ◽  
Geoff Chong ◽  
Michael Gilbertson ◽  
Andrew Grigg ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Nk Cell ◽  
Single Agent ◽  
Stage Iv ◽  
Complete Response ◽  
Phase 2 ◽  
Open Label ◽  
Immune Priming ◽  
Biomarker Analysis

7560 Background: Standard of care immunochemotherapy in front-line (1L) follicular lymphoma (FL) is highly efficacious but not without significant toxicity. High rates of grade 3-5 adverse events (AEs), primarily infection and bone marrow suppression, are experienced in up to 75% of patients. A more tolerable but equally effective approach is required. PD-1 inhibition, in combination with rituximab (R), increases T cell anti-tumour effect & enhances NK cell antibody dependent cell cytotoxicity, with proven efficacy in relapsed FL. The concept of ‘priming’ the immune system with nivolumab (N) prior to tumour-directed therapy has rationale and evidence, but the safety of this approach in 1L FL is not described. Methods: ‘1st FLOR’ (NCT03245021) is an open-label, multi-centre, phase 2, Simon’s 2-stage study of N + R (N = 39). Key eligibility were stage III-IV grade 1-3A FL requiring 1L systemic therapy; ECOG ≤2; adequate organ function. All patients (pts) receive induction N 240mg IV 2-weekly for 4 cycles. Pts with complete response (CR) receive 4 further cycles of 240mg IV N monotherapy then 12 cycles of maintenance N 480mg IV 4-weekly. Pts with < CR had 240mg N plus 375mg/m2 IV R 2-weekly for 4 cycles followed by maintenance N+R (N 480mg 4 weekly for 12 cycles; R 12 weekly for 8 cycles). Primary endpoint (EP) was ≥ G3 toxicity rate during induction. Secondary EPs; response rate by Lugano response criteria, overall toxicity, PFS, OS. Results: Between September 2017 to March 2020, 39 pts were enrolled. Baseline characteristics included median age of 54 (range: 28-79). stage IV disease in 67%, B Symptoms & bulk (≥7cm) in 23% each, intermediate-high risk FLIPI in 74%. The primary EP was met, with only 16 pts (41%) having ≥G3 toxicity at end of induction. Non-immune AEs were predominantly G1-2; most commonly infection (67%) & fatigue (64%). G3-4 Immune-related AEs were infrequent and included pancreatitis plus hepatitis (N = 1), pancreatitis alone (N = 1), rash (N = 1), transaminitis (N = 2), hypocortisolism (N = 1), hyperglycaemia (N = 3) and asymptomatic lipase/amylase increase (N = 3). Median follow-up was 17.5 months (range: 7-39). Overall response rate was 92% (36/39) with CR in 54% (21/39). Median time to CR was 5 months (m) (range: 2-25). Nine pts (23%) discontinued treatment; 7 due to progressive disease (1 pt died of transformed FL), 2 developed constitutional symptoms (1 stable disease, 1 partial response). In 25 evaluable pts, 12m PFS & OS is 72% (CI 51-88) & 96% (CI 80-100). Biomarker analysis is in progress. Conclusions: Immune-priming with single-agent N, then combination N+R in 1L FL is associated with favourable toxicity and high ORR & CR rates potentially providing an alternative to chemotherapy. Acknowledgements: Bristol-myers Squibb provided funding and nivolumab for this study. Clinical trial information: NCT03245021.

Accelerated R-COP: A Pilot Study for the Treatment of Advanced Low Grade Lymphomas that Has a High Complete Response Rate

2009 ◽  
Vol 21 (4) ◽  
pp. 434-438 ◽  
Author(s):  
M.J. Levitt ◽  
M. Gharibo ◽  
R. Strair ◽  
D. Schaar ◽  
A. Rubin ◽  
...  
Keyword(s):  
Pilot Study ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Low Grade
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