Phase III Intergroup Study of Fludarabine Phosphate Compared With Cyclophosphamide, Vincristine, and Prednisone Chemotherapy in Newly Diagnosed Patients With Stage III and IV Low-Grade Malignant Non-Hodgkin's Lymphoma

2006 ◽  
Vol 24 (10) ◽  
pp. 1590-1596 ◽  
Author(s):  
Anton Hagenbeek ◽  
Houchingue Eghbali ◽  
Silvio Monfardini ◽  
Umberto Vitolo ◽  
Peter J. Hoskin ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Fludarabine Phosphate ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. Patients and Methods Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients. Conclusion Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.

Rituximab Anti-CD20 Monoclonal Antibody Therapy in Non-Hodgkin’s Lymphoma: Safety and Efficacy of Re-Treatment

2000 ◽  
Vol 18 (17) ◽  
pp. 3135-3143 ◽  
Author(s):  
Thomas A. Davis ◽  
Antonio J. Grillo-López ◽  
Christine A. White ◽  
Peter McLaughlin ◽  
Myron S. Czuczman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Low Grade ◽  
Phase Iii Trial ◽  
Safety And Efficacy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20

PURPOSE: This phase II trial investigated the safety and efficacy of re-treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with low-grade or follicular non-Hodgkin’s lymphoma who relapsed after a response to rituximab therapy. PATIENTS AND METHODS: Fifty-eight patients were enrolled onto this study, and two were re-treated within the study. Patients received an intravenous infusion of 375 mg/m2 of rituximab weekly for 4 weeks. All patients had at least two prior therapies and had received at least one prior course of rituximab, with a median interval of 14.5 months between rituximab courses. RESULTS: Most adverse experiences (AEs) were transient grade 1 or 2 events occurring during the treatment period. Clinically significant myelosuppression was not observed; hematologic toxicity was generally mild and reversible. No patient developed human antichimeric antibodies after treatment. The type, frequency, and severity of AEs in this study were not apparently different from those reported in the phase III trial of rituximab. The overall response rate in 57 assessable patients was 40% (11% complete response and 30% partial responses). Median time to progression (TTP) in responders and median duration of response (DR) have not been reached, but Kaplan-Meier estimated medians are 17.8 months (range, 5.4+ to 26.6 months) and 16.3 months (range, 3.7+ to 25.1 months), respectively. These estimated medians are longer than the medians achieved in the patients’ prior course of rituximab (TTP and DR of 12.4 and 9.8 months, respectively, P > .1) and in a previously reported phase III trial (TTP in responders and DR of 13.2 and 11.6 months, respectively). Responses are ongoing in seven of 23 responders. CONCLUSION: In this re-treatment population, safety and efficacy were not apparently different from those after initial rituximab exposure.

Results of Multicentre Phase IV Study of Rituximab in Combination with CHOP Chemotherapy in Patients with Previously Untreated Non-Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4624-4624
Author(s):  
Ti Shen ◽  
Zhongzhen Guan ◽  
Zhixiang Shen ◽  
Yuankai She ◽  
Jun Zhu
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Response Rate ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Newly Diagnosed ◽  
Chop Chemotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Phase Iv

Abstract Purpose: Rituximab is a chimeric anti-CD20 monoclonal antibody that was the first antibody approved by the FDA in the United States of America and SDA in China for the treatment of B-cell non-Hodgkin’s Lymphoma (NHL). It has shown significant efficacy and good tolerability in refractory and relapsed NHL. We have conducted a multicenter phase IV trial to evaluate the efficacy and safety of rituximab combined with standard CHOP chemotherapy in patients with newly diagnosed B-NHL. Methods: Patients with newly diagnosed, histologically proven CD20-positive NHL were eligible for the study. All patients received 4–6 infusions of rituximab (375mg/m2 per dose) in combination with CHOP chemotherapy, either concurrently (rituximab administered on the first day of each 21-day CHOP cycle) or sequentially (4–6 once-weekly infusions of rituximab followed by six 21-day cycles of CHOP). Each CHOP cycle consisted of cyclophosphamide 750 mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (maximum 2.0mg/dose) given intravenously on day 1, and prednisone 100mg/day orally on days 1-5. Tumor responses were assessed at the end of treatment. Results: A total of 347 patients were recruited between February 2002 and December 2003. Of these 235 (68%) were male and 94 (27%) aged >60. The main lymphoma subtypes were diffuse large B-cell 196 (56%), follicular 41(12%), small lymphocytic/chronic lymphocytic leukemia 13(4%) and MALT 11(3%). Ann Arbor staging was as follows: stage I, 52 (15%); stage II, 80 (23%); stage III, 90(26%); stage IV, 105(30%); twenty patients (6%) could not be assessed. Of the 347 patients enrolled, 314 were evaluable for response. An objective response was observed in 94% of evaluable patients with a complete response (CR) in 56%, stable disease in 3.8% and progressive disease in 2.5%. The complete response rate was 63% for patients receiving 6 cycles of rituximab and 54% for those receiving four cycles of rituximab. No difference in response rate was observed between the sequential and concurrent groups. The most common adverse events were leucopenia in 122 patients (35%), nausea and vomiting 66 (19%), fever 39 (11%), rash 15 (4%) and asthma 4 (1%). Conclusion: The combination of rituximab and CHOP chemotherapy is an effective and well-tolerated treatment for patients with newly-diagnosed CD20-positive NHL. The safety and efficacy achieved in this study suggests that more than four doses of rituximab may be required for optimal efficacy.

Prolonged Clinical and Molecular Remission in Patients With Low-Grade or Follicular Non-Hodgkin's Lymphoma Treated With Rituximab Plus CHOP Chemotherapy: 9-Year Follow-Up

2004 ◽  
Vol 22 (23) ◽  
pp. 4711-4716 ◽  
Author(s):  
Myron S. Czuczman ◽  
Robin Weaver ◽  
Baha Alkuzweny ◽  
Judy Berlfein ◽  
Antonio J. Grillo-López
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Molecular Remission ◽  
Prior Chemotherapy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose Long-term follow-up with updated time to disease progression (TTP) and duration of response (DR) data are presented from a multicenter, phase II trial of rituximab/cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) combination therapy in 40 patients with CD20+, B-cell, non-Hodgkin's lymphoma (NHL). Revised response rates based on International Workshop Response Criteria are also provided. Patients and Methods Enrollment began in April 1994 and consisted of patients with histologically confirmed, low-grade, B-cell lymphoma who had received no prior chemotherapy or who had no more than four prior standard therapies. Patients received six cycles of CHOP and six infusions of rituximab. Results Eight (21%) of the 38 treated patients were classified as International Working Formulation (IWF) A, 16 (42%) were IWF B, 13 (34%) were IWF C, and one (3%) was IWF D. Nine (24%) of 38 patients had received prior chemotherapy. Nine (24%) of 38 were considered poor risk according to the Follicular Lymphoma International Prognostic Index. Overall response rate was 100%; 87% of patients achieved a complete response or unconfirmed complete response. The median TTP and DR were 82.3 months and 83.5 months, respectively. Seven of eight patients who were bcl-2 positive at baseline converted to negative, and three of the seven patients have sustained the molecular remission. Conclusion Although a cure has not been found yet for follicular NHL, the R-CHOP combination provides a lengthy response duration in patients with relapsed or newly diagnosed indolent NHL.

Phase II Window Study on Rituximab in Newly Diagnosed Pediatric Mature B-Cell Non-Hodgkin's Lymphoma and Burkitt Leukemia

2010 ◽  
Vol 28 (19) ◽  
pp. 3115-3121 ◽  
Author(s):  
Andrea Meinhardt ◽  
Birgit Burkhardt ◽  
Martin Zimmermann ◽  
Arndt Borkhardt ◽  
Udo Kontny ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
B Cell Lymphoma ◽  
Corticosteroid Treatment ◽  
Hodgkin's Lymphoma ◽  
Newly Diagnosed ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose The activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL. Patients and Methods Patients younger than age 19 years with CD20+ B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m2 administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had ≥ 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity. Results From April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007). Conclusion Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.

Bendamustine in Patients With Rituximab-Refractory Indolent and Transformed Non-Hodgkin's Lymphoma: Results From a Phase II Multicenter, Single-Agent Study

2008 ◽  
Vol 26 (2) ◽  
pp. 204-210 ◽  
Author(s):  
Jonathan W. Friedberg ◽  
Philip Cohen ◽  
Ling Chen ◽  
K. Sue Robinson ◽  
Andres Forero-Torres ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Patients Âgés ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Duration Of Response

PurposeBendamustine hydrochloride is an alkylating agent with novel mechanisms of action. This phase II multicenter study evaluated the efficacy and toxicity of bendamustine in patients with B-cell non-Hodgkin's lymphoma (NHL) refractory to rituximab.Patients and MethodsPatients received bendamustine 120 mg/m2intravenously on days 1 and 2 of each 21-day cycle. Outcomes included response, duration of response, progression-free survival, and safety.ResultsSeventy-six patients, ages 38 to 84 years, with predominantly stage III/IV indolent (80%) or transformed (20%) disease were treated; 74 were assessable for response. Twenty-four (32%) were refractory to chemotherapy. Patients received a median of two prior unique regimens. An overall response rate of 77% (15% complete response, 19% unconfirmed complete response, and 43% partial) was observed. The median duration of response was 6.7 months (95% CI, 5.1 to 9.9 months), 9.0 months (95% CI, 5.8 to 16.7) for patients with indolent disease, and 2.3 months (95% CI, 1.7 to 5.1) for those with transformed disease. Thirty-six percent of these responses exceeded 1 year. The most frequent nonhematologic adverse events included nausea and vomiting, fatigue, constipation, anorexia, fever, cough, and diarrhea. Grade 3 or 4 reversible hematologic toxicities included neutropenia (54%), thrombocytopenia (25%), and anemia (12%).ConclusionSingle-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL. These findings are promising and will serve as a benchmark for future clinical trials in this novel patient population.

Interferon Alfa Consolidation After Intensive Chemotherapy Does Not Prolong the Progression-Free Survival of Patients With Low-Grade Non-Hodgkin’s Lymphoma: Results of the Southwest Oncology Group Randomized Phase III Study 8809

2000 ◽  
Vol 18 (10) ◽  
pp. 2010-2016 ◽  
Author(s):  
Richard I. Fisher ◽  
Bruce W. Dana ◽  
Michael LeBlanc ◽  
Carl Kjeldsberg ◽  
Jeffrey D. Forman ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Progression Free Survival ◽  
Interferon Alfa ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Low Grade ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE: S8809 is a randomized phase III trial determining whether intensive cytoreductive treatment, followed by interferon consolidation at the time of minimal residual disease, prolongs the progression-free survival (PFS) or overall survival (OS) of indolent lymphoma patients. PATIENTS AND METHODS: Five hundred seventy-one patients with previously untreated stage III or IV low-grade non-Hodgkin’s lymphoma were registered. Patients received six to eight cycles of prednisone, methotrexate, doxorubicin, cyclophosphamide, and etoposide/mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE[day 1]-MOPP[day 8]) chemotherapy or chemotherapy plus radiotherapy. Responding patients were randomized to observation alone or to interferon consolidation. Interferon alfa-2b 2 mU/m2 was given subcutaneously three times weekly for 2 years. RESULTS: Two hundred sixty-eight eligible patients were randomized to interferon alfa consolidation (n = 144) or observation alone (n = 124). With a median follow-up time from randomization among patients still alive of 6.2 years, the median PFS time was 4.1 years for patients who received interferon consolidation therapy and 3.2 years for patients who were observed after ProMACE-MOPP induction (P = .25). The adjusted hazard ratio for relapse for observation to interferon was 0.83 (95% confidence interval [CI], 0.61 to 1.13). The median OS has not been reached in either group. At 5 years, OS is 78% for the interferon group and 77% for the observation group (P = .65). The adjusted hazard ratio for survival for observation to interferon is 1.11 (95% CI, 0.69 to 1.79). CONCLUSION: Interferon alfa consolidation therapy after intensive treatment with anthracycline-containing combination chemotherapy and involved-field radiation therapy does not prolong the PFS or OS of patients with low-grade non-Hodgkin’s lymphoma.

scholarly journals Gemcitabine as a single agent in the treatment of relapsed or refractory low-grade non-Hodgkin's lymphoma

2001 ◽  
Vol 113 (3) ◽  
pp. 772-778 ◽  
Author(s):  
C. Dumontet ◽  
F. Morschhauser ◽  
P. Solal-Celigny ◽  
F. Bouafia ◽  
Emmanuelle Bourgeois ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Phase II Study of Oral Fludarabine Phosphate in Relapsed Indolent B-Cell Non-Hodgkin's Lymphoma

2006 ◽  
Vol 24 (1) ◽  
pp. 174-180 ◽  
Author(s):  
Kensei Tobinai ◽  
Takashi Watanabe ◽  
Michinori Ogura ◽  
Yasuo Morishima ◽  
Yoshiaki Ogawa ◽  
...  
Keyword(s):  
B Cell ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Response Rate ◽  
Phase Ii Study ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Fludarabine Phosphate ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose Although intravenous (IV) fludarabine phosphate is effective against indolent B-cell non-Hodgkin's lymphoma (B-NHL), IV administration for 3 to 5 consecutive days is inconvenient in an outpatient setting. To assess the efficacy and toxicity of oral fludarabine phosphate in patients with indolent B-NHL, we conducted a multicenter phase II study. Patients and Methods Patients with relapsed indolent B-NHL received fludarabine phosphate tablets orally once daily on days 1 through 5 every 28 days for three to six cycles. The efficacy was separately analyzed in a mantle-cell lymphoma (MCL) cohort and indolent B-NHL except for MCL (IL) cohort. The primary end point was the overall response rate (ORR). Results Fifty-two patients, including 46 in the IL cohort (41 with follicular lymphoma) and six in the MCL cohort, were registered, and all patients were eligible. Forty-one patients (79%) had received rituximab as prior therapy. In the IL cohort, the ORR and complete response rate were 65% (30 of 46 patients; 95% CI, 50% to 79%) and 30% (14 of 46 patients; 95% CI, 18% to 46%), respectively. One of six patients with MCL achieved a partial response. The median times to treatment failure for the 46 patients in the IL cohort and for the six patients in the MCL cohort were 8.6 and 6.1 months, respectively. Hematologic toxicities, including grade 4 neutropenia (37%), were the most frequent toxicities, and nonhematologic toxicities were mild. Conclusion Oral fludarabine phosphate is highly effective in patients with relapsed indolent B-NHL who have mostly been pretreated with rituximab and is more convenient than the IV formulation.

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