Secondary efficacy subanalysis by histology from the phase III BRIGHT study: First-line bendamustine-rituximab (BR) compared with standard R-CHOP/R-CVP for patients with advanced indolent non-Hodgkin lymphoma (NHL) or mantle cell lymphoma (MCL).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8537-8537 ◽  
Author(s):  
Ian Flinn ◽  
Richard H. C. Van Der Jagt ◽  
Brad S. Kahl ◽  
Peter Wood ◽  
Tim E. Hawkins ◽  
...  
Keyword(s):  
Standard Treatment ◽  
Complete Response ◽  
Phase Iii ◽  
Non Hodgkin Lymphoma ◽  
Small Subgroup ◽  
Mantle Cell ◽  
Efficacy Measure ◽  
Treatment Naïve ◽  
Independent Review ◽  
Efficacy Assessment

8537 Background: BR was previously reported to be statistically noninferior to R-CVP/R-CHOP for complete response rate in the treatment of patients with indolent NHL or MCL. Evaluation of time-to-event outcomes is immature. This subanalysis reports response by histology. Methods: Indolent NHL or MCL was histologically confirmed <6 months before study enrollment in patients who were therapy-naïve. Patients were stratified according to predetermined standard treatment (R-CHOP or RECVP) and lymphoma type, then assigned to receive BR (28-day cycles: bendamustine 90 mg/m2 on days 1 and 2, rituximab 375 mg/m2on day 1) or standard treatment (21-day cycles at standard doses) for 6-8 cycles. Responses were assessed by a blinded independent review committee. The primary efficacy measure was noninferiority of BR complete response (CR) rate for evaluable patients with ≥1 postbaseline efficacy assessment. If the noninferiority threshold was met, superiority was assessed. Secondary measures included tolerability. Results: Of 447 patients enrolled in the study, 213 receiving BR and 206 receiving R-CHOP/R-CVP were evaluable with postbaseline data (Table). BR achieved a statistically noninferior CR rate compared with R-CHOP/R-CVP in patients with indolent NHL and MCL. Conclusions: In patients with treatment-naïve indolent NHL and MCL, BR achieved the primary endpoint of noninferior CR rate. Most CR rates were numerically, but not significantly, higher with BR. Small subgroup results should be interpreted with caution. Support: Teva BPP R&D, Inc. Clinical trial information: NCT00877006. [Table: see text]

ALPINE: Phase III zanubrutinib (BGB-3111) versus ibrutinib in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS7572-TPS7572 ◽  
Author(s):  
Peter Hillmen ◽  
Jennifer R. Brown ◽  
John C. Byrd ◽  
Barbara Eichhorst ◽  
Nicole Lamanna ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Geographic Region ◽  
Lymphocytic Leukemia ◽  
Phase Iii ◽  
Open Label ◽  
Duration Of Response ◽  
Treatment Naïve ◽  
Independent Review ◽  
Ecog Ps

TPS7572 Background: Inhibition of Bruton tyrosine kinase (BTK) has emerged as a strategy for targeting B-cell malignancies including CLL/SLL. Zanubrutinib, an investigational inhibitor of BTK, was specifically engineered to optimize selectivity, half-life and solubility in an effort to decrease toxicities and better penetrate tumor tissue. Early clinical data suggested that zanubrutinib treatment in patients with treatment-naïve (TN; n = 16) or R/R (n = 50) CLL/SLL induced deep responses: 94% overall response rate (ORR), including 6% and 2% complete response rates in TN and R/R CLL/SLL, respectively (ICML 2017). This study is designed to evaluate whether zanubrutinib monotherapy exhibits non-inferior and potentially superior efficacy based on the ORR vs ibrutinib monotherapy in patients with R/R CLL/SLL. Methods: This ongoing phase 3, randomized, open-label, global study (NCT03734016, BGB-3111-305) is comparing the efficacy and safety of zanubrutinib vs ibrutinib in adult patients with R/R CLL/SLL. Approximately 400 patients will be randomized, 1:1 to each arm and stratified by age (< 65 vs ≥ 65 years), refractory status (yes vs no), geographic region, and del(17p)/ TP53 mutation status (present vs absent). Key inclusion criteria include R/R CLL/SLL requiring treatment per iwCLL criteria, ECOG PS 0-2, and adequate hematologic function. The primary endpoint is ORR as determined by an independent review committee according to iwCLL guidelines, with modification for treatment-related lymphocytosis for patients with CLL and per 2014 Lugano Classification for patients with SLL. The study is powered to test the non-inferiority and superiority of the ORR for zanubrutinib vs ibrutinib. Secondary endpoints include progression-free survival, safety, duration of response, and overall survival. Recruitment is ongoing. Clinical trial information: NCT03734016.

Phase III Study of VCAP-AMP-VECP vs. Biweekly CHOP in Aggressive Adult T-Cell Leukemia-Lymphoma (ATLL): Japan Clinical Oncology Group Study, JCOG9801.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 812-812 ◽  
Author(s):  
Kunihiro Tsukasaki ◽  
Takuya Fukushima ◽  
Atae Utsunomiya ◽  
Syuichi Ikeda ◽  
Masato Masuda ◽  
...  
Keyword(s):  
Cox Regression ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Rank Test ◽  
P Value ◽  
Minimization Method ◽  
Adult T Cell Leukemia ◽  
Non Hodgkin Lymphoma

Abstract Background: In our study for non-Hodgkin lymphoma (NHL) in 1980’s (JCOG8701), human T-lymphotropic virus type-1- associated ATLL was the poorest prognostic subtype in NHL. The complete response (CR) rate was 42%, the median survival time (MST) was 8 months, and the 4-yr overall survival (OS) was 12% (Proc ASCO13:378, 1994). Our previous phase II study (JCOG9303) of G-CSF-supported, dose-intensified multi-agent chemotherapy with VCAP (vincristine, cyclophosphamide, doxorubicin, prednisolone), AMP (doxorubicin, ranimustine, prednisolone) and VECP (vindesine, etoposide, carboplatin, prednisolone) with intrathecal prophylaxis for aggressive ATLL, showed promising results with response rate (RR) of 81% and MST of 13 months (Br J Haematol113:375,2001). To test the superiority of this VCAP-AMP-VECP regimen over biweekly-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone), we conducted a phase III trial. Methods: Previously untreated patients (pts) with aggressive ATLL, acute-, lymphoma- or unfavorable chronic-type, were randomized either to receive 6 courses of VCAP-AMP-VECP every 4 weeks (arm A) or 8 courses of biweekly-CHOP (arm B) with minimization method balancing performance status and institution. Both regimens were supported with G-CSF and intrathecal prophylaxis using cytarabine, methotrexate and prednisolone. Eligibility included preserved organ functions and aged 15–69 years. Primary endpoint was OS to be compared by log-rank test. Assuming 60 eligible pts in each arm, the study had 0.8 power to detect a 15% difference in 3-year OS at 0.05 one-sided alpha. Results: 118 pts (57 in arm A, 61 in arm B) were randomized between 07/98 and 10/03. Median follow-up time in all randomized pts was 11.0 months at 12/04. 72 % of the pts responded, with 23 pts achieving CR (40%) and 18 achieving partial response (PR; 32%) in arm A. The RR was 66%, with 15 pts achieving CR (25%) and 25 achieving PR (41%) in arm B. The median progression-free survival (PFS) time and PFS at one-year in arm A were 7.0 months and 28.1%, respectively, whereas 5.4 months and 16.2% in arm B. The MST and OS at 3 years in arm A were 12.7 months and 23.6%, respectively, whereas 10.9 months and 12.7% in arm B. Log-rank p-value for primary end point, OS, was 0.085. After adjustment of patients’ characteristics at registration by Cox regression, the p value became 0.029 because of unbalanced prognostic factors such as bulky lesion. In arm A vs. arm B, %G4 neutropenia, %G4 thrombocytopenia and %G4 infection were 98% vs. 83%, 74% vs. 17% and 7% vs. 3%, respectively. Three toxic deaths were reported in arm A. Conclusions: These results demonstrate that VCAP-AMP-VECP yields longer OS time than biweekly-CHOP but with higher toxicity profiles that are acceptable, and suggest that the former regimen should be the standard therapy for aggressive ATLL.

Phase 2 study of suberoylanilide hydroxamic acid (SAHA) in relapsed or refractory indolent non-Hodgkin lymphoma: A California Cancer Consortium study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18515-18515 ◽  
Author(s):  
M. Kirschbaum ◽  
J. Zain ◽  
L. Popplewell ◽  
V. Pullarkat ◽  
N. Obadike ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Hydroxamic Acid ◽  
Marginal Zone ◽  
Ct Scanning ◽  
Complete Response ◽  
Marginal Zone Lymphoma ◽  
Clinical Activity ◽  
Rapid Progression ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell

18515 Background: The indolent (follicular, marginal zone and mantle cell) lymphomas tend to recur with decreasing intervals of remission post standard chemotherapy. Vorinostat (SAHA, Zolinza), an orally administered hydroxamic acid histone deacetylase inhibitor with activity against class I and II deactylases, with preclinical and clinical activity against various forms of lymphoma, is being studied in patients with relapsed or refractory indolent lymphoma. Methods: Patients with relapsed or refractory follicular, marginal zone, or mantle cell lymphoma are eligible. Vorinostat is dosed at 200 mg po twice daily for 14 consecutive days on a 21 day cycle. CT scanning and marrow biopsy is performed after every three cycles. Patients may have received up to four prior chemotherapy regimens including Zevalin or Bexxar; previous transplant is allowed. Results: 15 patients (9 female, 6 male) have been enrolled thus far. Median age is 64 (40- 78) years One patient was found to have coexisting DLBCL and was removed from study. Four patients were taken off study due to progression, three stopped due to toxicity (fatigue in a 73 yo woman who had stable to improved marginal zone lymphoma after 10 cycles, fatigue and atrial fibrillation in a 65 yo man after 7 cycles, diarrhea in a 78 year old woman after 2 cycles). Complete Response (CR) in a patient with follicular lymphoma was attained after 9 cycles, this CR persists now for eight months at the time of abstract submission off therapy. A partial response (PR) was seen in a 40 yo man with lymphoma progression despite multiple rounds of therapy, with rapidly expanding masses just prior to starting vorinostat, the largest of which was 16x12.3 cm. This lesion currently measures 7.2x4.6 cm, with disappearance of many other sites; patient continues on vorinostat. Three of the patients with continued stable disease beyond 9 cycles have marginal zone lymphoma, while the two responders (CR or PR) have follicular lymphoma. A patient with PET resolution and decreases in two of the involved sites stopping after 10 cycles due to fatigue, developed rapid progression three months after stopping vorinostat. Conclusions: Vorinostat demonstrates preliminary activity against follicular and marginal zone lymphoma. No significant financial relationships to disclose.

scholarly journals Bendamustine in the treatment of B-cell non-Hodgkin lymphoma

2018 ◽  
Vol 20 (4) ◽  
pp. 41-46
Author(s):  
L G Babicheva ◽  
I V Poddubnaya
Keyword(s):  
Clinical Data ◽  
Therapeutic Index ◽  
Daily Practice ◽  
Phase Iii ◽  
Cross Resistance ◽  
Skin Reactions ◽  
Non Hodgkin Lymphoma ◽  
Antiemetic Prophylaxis ◽  
Mantle Cell ◽  
Phase Iii Trials

Bendamustine is a uniquely structuredalkylating agent that lacks cross-resistance with other alkylators. This agent has a high degreeof activity against a variety of tumor cell lines.Based on clinical data from randomized phase III trials, bendamustine, with or without rituximab, hasbeen shown to be an appropriate option for first-line treatment or treatment of relapsed/refractory patients with indolent non-Hodgkin’s lymphoma or elderly patients with mantle cell lymphoma. Bendamustine treatment is associated with abetter therapeutic index and offers an improved overall quality of life compared to R-CHOP or R-CVP. It is now often used as achemotherapy backbone for combination with novel drugs including ibrutinib or idelalisib. This article provides a comprehensivesummaryof the clinical data along with practical adviceonhowto optimallymanagepatients with bendamustine therapy, includingdose recommendations, antiemetic prophylaxis, prevention of infusion and skin reactions, as well as prophylaxis of opportunisticinfections. This information might be helpful for clinicians using bendamustine in their daily practice.

scholarly journals Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab in Patients with Relapsed Follicular, Indolent, or Mantle Cell Lymphomas – 8-Year Follow-up Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 145-145 ◽  
Author(s):  
Mathias J. Rummel ◽  
Christina Balser ◽  
Ulrich Kaiser ◽  
Hans Peter Böck ◽  
Martina Beate Stauch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Response Rate ◽  
Complete Response ◽  
Phase Iii ◽  
Rituximab Maintenance ◽  
Mantle Cell ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Indolent Lymphomas

Abstract Introduction: Fludarabine plus rituximab (F-R) is an established treatment option for patients (pts) with relapsed/refractory follicular lymphoma (FL), other indolent lymphoma, or mantle cell lymphoma (MCL). To further improve the treatment in this setting we initiated in 2003 a multicenter, randomized phase III study to compare the efficacy and safety of bendamustine plus rituximab (B-R) versus F-R for pts with relapsed FL, other indolent lymphomas or MCL. Patients and Methods: 230 pts in need of treatment were randomized to rituximab 375 mg/m² (day 1) plus either bendamustine 90 mg/m² (days 1+2) or fludarabine 25 mg/m² (days 1–3) q 28 days for a maximum of 6 cycles. Prophylactic use of antibiotics or granulocyte-colony stimulating factor (G-CSF) was not generally recommended; however, in case of severe granulocytopenia, G-CSF use was permitted. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), overall response rate (ORR), and complete response rate (CR). The protocol was amended in 2006 to allow rituximab maintenance therapy (rituximab 375 mg/m2 q 3 months for up to 2 years) in both arms, following regulatory approvals in this setting. Results: A total of 219 pts were evaluable for the analysis (114 B-R; 105 F-R). There were no significant differences between arms for patient characteristics, including age, stage, LDH, IPI, FLIPI, bone marrow infiltration, and extranodal involvement. Most pts had stage IV (71.6% B-R; 60.6% F-R) or stage III disease (21.1% B-R; 25.3% F-R). Median patient age was 68 yrs (range 38–87). Patients had received a median of 1 prior therapy (range 1–7). Histological subtypes were distributed equally between the B-R and F-R arms: follicular, 45.9% and 47.5%, respectively; Waldenström’s Macroglobulinemia, 11.9% and 11.1%; MCL, 20.2% and 21.2%; other indolent lymphomas, 23% and 20.2%. A median of 6 cycles were given in both treatment arms, with 75.2% and 53.4% of B-R and F-R pts receiving 6 cycles, respectively. At the time of this analysis (June 2014), the median observation time was 96 months. The ORR was significantly higher with B-R than with F-R (83.5% vs. 52.5%, respectively; p< 0.0001). The CR rate with B-R was also significantly higher than that with F-R (38.5% vs. 16.2%; p=0.0004). Median PFS was significantly prolonged with B-R compared with F-R (34 vs. 12 months; hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.38–0.72; p<0.0001). The longer PFS translated into a survival benefit with a significantly longer median overall survival in the B-R group than in the F-R group (110 vs. 49 months; HR 0.64, 95% CI 0.45–0.91; p=0.0125) comprising 55 and 71 deaths in the B-R and F-R groups, respectively. There were no significant differences in the rates of alopecia, stomatitis, erythema, allergic reactions, peripheral neuropathy, or infectious episodes between groups. Hematologic toxicities were also similar between arms: 8.9% grade 3/4 neutropenia with B-R vs. 9.1% with F-R; 11.8% grade 3/4 leukocytopenia with B-R vs. 12.4% with F-R. The overall incidence of serious adverse events was similar for the B-R and F-R groups (17.4% and 22.2%, respectively). 17 pts (14.9%) developed a secondary neoplasia after B-R compared with 16 pts (15.2%) after F-R. Of these, 5 pts in the B-R group, and 3 pts in the F-R group developed a secondary hematological neoplasia (2 AML [1 AML M4], 1 CML, 1 DLBCL, and 1 HD after B-R; and 2 AML M4, and 1 MDS after F-R). An unplanned subanalysis showed that rituximab maintenance therapy significantly prolonged overall survival (HR 0.38, 95% CI 0.32-0.71; p=0.0003) and PFS (HR 0.35, 95% CI 0.31-0.62; p< 0.0001) in the small group of 40 pts who received this treatment (23 B-R, 17 F-R) compared with those who did not. Although the numbers are too small in this non-randomized comparison to draw validated conclusions, these results appear to confirm the favorable role of rituximab maintenance. Conclusions: B-R was more effective than F-R in this setting of relapsed FL, other indolent lymphomas and MCL due to higher overall and complete response rates, a longer PFS, and an improved OS. These data confirm the high anti-lymphoma activity of B-R. Disclosures Off Label Use: Indication and dosage of bendamustine.

First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7500-7500 ◽  
Author(s):  
Ian Flinn ◽  
Richard van der Jagt ◽  
Julie E. Chang ◽  
Peter Wood ◽  
Tim E. Hawkins ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Complete Response ◽  
Rank Test ◽  
First Line ◽  
Open Label ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Duration Of Response ◽  
Treatment Naïve

7500 Background: BRIGHT, a phase 3, open-label, noninferiority study comparing efficacy and safety of bendamustine plus rituximab (BR) vs rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP) in treatment-naive patients (pts) with indolent non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL), showed that the complete response rate for first-line BR was statistically noninferior to R-CHOP/R-CVP ( Blood 2014). Pts were monitored for ≥5 years (yr) to assess the overall effect of BR or R-CHOP/R-CVP in a controlled clinical setting. This analysis reports the time-to-event variables of the 5-yr follow-up (FU) study. Methods: Pts with iNHL or MCL randomized to 6-8 cycles of BR or R-CHOP/R-CVP underwent complete assessments at end of treatment, then were monitored regularly. Progression-free survival (PFS), event-free survival (EFS), duration of response (DOR) and overall survival (OS) were compared using a stratified log-rank test. Results: Of 447 randomized pts, 224 received BR, 104 R-CHOP, and 119 R-CVP; 419 entered the FU. The median FU time was 65.0 and 64.1 months for BR and R-CHOP/R-CVP, respectively. The 5-yr PFS rate was 65.5% (95% CI 58.5-71.6) and 55.8% (48.4-62.5), and OS was 81.7% (75.7-86.3) and 85% (79.3-89.3) for BR and R-CHOP/R-CVP, respectively. The hazard ratio (95% CI) for PFS was 0.61 (0.45-0.85; P= .0025), EFS 0.63 (0.46-0.84; P= .0020), DOR 0.66 (0.47-0.92; P= .0134), and OS 1.15 (0.72-1.84; P= .5461) comparing BR vs R-CHOP/R-CVP. Similar results were found in iNHL [PFS 0.70 (0.49-1.01; P= .0582)] and MCL [PFS 0.40 (0.21-0.75; P= .0035)], with the strongest effect in MCL. Use of R maintenance was similar, 43% in BR and 45% in R-CHOP/R-CVP. B was included as second-line in 27 (36%) of the 75 pts requiring therapy who originally received R-CHOP/R-CVP. Comparable safety profiles with expected adverse events were observed in the FU study in BR vs R-CHOP/R-CVP. Conclusions: The long-term FU of the BRIGHT study has confirmed that PFS, EFS, and DOR were significantly better for BR, and OS was not statistically different between BR and R-CHOP/R-CVP. The safety profile was as previously reported. Clinical trial information: NCT00877006.

Combination of Rituximab, Bendamustine, and Cytarabine for Patients With Mantle-Cell Non-Hodgkin Lymphoma Ineligible for Intensive Regimens or Autologous Transplantation

2013 ◽  
Vol 31 (11) ◽  
pp. 1442-1449 ◽  
Author(s):  
Carlo Visco ◽  
Silvia Finotto ◽  
Renato Zambello ◽  
Rossella Paolini ◽  
Andrea Menin ◽  
...  
Keyword(s):  
International Prognostic Index ◽  
Autologous Transplantation ◽  
Prognostic Index ◽  
Progression Free Survival ◽  
Response Duration ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Non Hodgkin Lymphoma ◽  
Positron Emission ◽  
Mantle Cell

Purpose The combination of bendamustine (B) and rituximab (R) is efficacious, with favorable toxicity in mantle-cell lymphoma (MCL). In this phase II study, we combined cytarabine with R and B (R-BAC) in patients with MCL age ≥ 65 years who were previously untreated or relapsed or refractory (R/R) after one prior immunochemotherapy treatment. Patients and Methods In stage one, we established the maximum-tolerated dose (MTD) of cytarabine in R-BAC. In stage two, patients received R (375 mg/m2 intravenously [IV] on day 1), B (70 mg/m2 IV on days 2 and 3), and cytarabine (MTD IV on days 2 to 4) every 28 days for four to six cycles. The primary end point (overall response rate [ORR]) was evaluated by positron emission tomography. Secondary end points included safety, progression-free survival (PFS), response duration, and overall survival. Results Forty patients (median age, 70 years; 20 previously untreated patients) were enrolled; 93% had Ann Arbor stage III/IV disease; 49% had high Mantle Cell International Prognostic Index scores, with 15% blastoid histology. All R/R patients (35% refractory) had previously received R-containing regimens. The cytarabine MTD used in stage two was 800 mg/m2, and R-BAC was well tolerated, with an 85% treatment completion rate. The major toxicity was transient grades 3 to 4 thrombocytopenia (87% of patients); febrile neutropenia occurred in 12%. The ORR was 100% (95% complete response [CR]) for previously untreated and 80% (70% CR) for R/R patients. The 2-year PFS rate (± standard deviation) was 95% ± 5% for untreated and 70% ± 10% for R/R patients. Conclusion R-BAC is well tolerated and active against MCL.

scholarly journals Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma

Blood ◽  
2010 ◽  
Vol 115 (15) ◽  
pp. 3008-3016 ◽  
Author(s):  
Joseph A. Sparano ◽  
Jeannette Y. Lee ◽  
Lawrence D. Kaplan ◽  
Alexandra M. Levine ◽  
Juan Carlos Ramos ◽  
...  
Keyword(s):  
Confidence Interval ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Standard Treatment ◽  
Oral Prednisone ◽  
Complete Response ◽  
Intravenous Bolus ◽  
Non Hodgkin Lymphoma ◽  
Phase 2 Trial ◽  
Immunocompetent Patients

Abstract Rituximab plus intravenous bolus chemotherapy is a standard treatment for immunocompetent patients with B-cell non-Hodgkin lymphoma (NHL). Some studies have suggested that rituximab is associated with excessive toxicity in HIVassociated NHL, and that infusional chemotherapy may be more effective. We performed a randomized phase 2 trial of rituximab (375 mg/m2) given either concurrently before each infusional etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy cycle or sequentially (weekly for 6 weeks) after completion of all chemotherapy in HIV-associated NHL. EPOCH consisted of a 96-hour intravenous infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by intravenous bolus cyclophosphamide given every 21 days for 4 to 6 cycles. In the concurrent arm, 35 of 48 evaluable patients (73%; 95% confidence interval, 58%-85%) had a complete response. In the sequential arm, 29 of 53 evaluable patients (55%; 95% confidence interval, 41%-68%) had a complete response. The primary efficacy endpoint was met for the concurrent arm only. Toxicity was comparable in the 2 arms, although patients with a baseline CD4 count less than 50/μL had a high infectious death rate in the concurrent arm. We conclude that concurrent rituximab plus infusional EPOCH is an effective regimen for HIV-associated lymphoma. This study is registered at http://clinicaltrials.gov as NCT00049036.

scholarly journals Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6450-6458 ◽  
Author(s):  
William G. Wierda ◽  
Thomas J. Kipps ◽  
Jan Dürig ◽  
Laimonas Griskevicius ◽  
Stephan Stilgenbauer ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Progression Free Survival ◽  
Complete Response ◽  
Lymphocytic Leukemia ◽  
Β2 Microglobulin ◽  
Phase 2 Trial ◽  
Treatment Naïve ◽  
Risk Patients ◽  
Independent Review ◽  
Grade 3

Abstract We conducted an international phase 2 trial to evaluate 2 dose levels of ofatumumab, a human CD20 mAb, combined with fludarabine and cyclophosphamide (O-FC) as frontline therapy for chronic lymphocytic leukemia (CLL). Patients with active CLL were randomized to ofatumumab 500 mg (n = 31) or 1000 mg (n = 30) day 1, with fludarabine 25 mg/m2 and cyclophosphamide 250 mg/m2 days 2-4, course 1; days 1-3, courses 2-6; every 4 weeks for 6 courses. The first ofatumumab dose was 300 mg for both cohorts. The median age was 56 years; 13% of patients had a 17p deletion; 64% had β2-microglobulin > 3.5 mg/L. Based on the 1996 National Cancer Institute Working Group (NCI-WG) guidelines, the complete response (CR) rate as assessed by an independent review committee was 32% for the 500-mg and 50% for the 1000-mg cohort; the overall response (OR) rate was 77% and 73%, respectively. Based on univariable regression analyses, β2-microglobulin and the number of O-FC courses were significantly correlated (P < .05) with CR and OR rates and progression-free survival (PFS). The most frequent Common Terminology Criteria (CTC) grade 3-4 investigator-reported adverse events were neutropenia (48%), thrombocytopenia (15%), anemia (13%), and infection (8%). O-FC is active and safe in treatment-naive patients with CLL, including high-risk patients. This trial was registered at www.clinicaltrials.gov as NCT00410163.

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