Phase II Study of Sphingosomal Vincristine in CHOP+/ − Rituximab for Patients with Aggressive Non-Hodgkin’s Lymphoma (NHL): Promising 3 Year Follow-Up Results in Elderly Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 943-943
Author(s):  
Maria Alma Rodriguez ◽  
Nam H. Dang ◽  
Luis Fayad ◽  
Andre Goy ◽  
Fredrick Hagemeister ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Standard Dose ◽  
Age Groups ◽  
B Cell Lymphoma ◽  
Younger Patients

Abstract Background: Individuals older than 60 years have a worse prognosis than younger patients with aggressive NHL. Vincristine is an active drug in the treatment of malignant lymphomas. Sphingosomal vincristine (SV) was well tolerated with 45% ORR in patients with multiple relapses of aggressive NHL (ASH abst. 412, 1999). Based on these data, a phase II study of CHOP with rituximab (no rituximab for T-cell histology), and substituting SV for free vincristine, was undertaken in patients with previously untreated aggressive NHL. Methods: Aggressive NHL histologies eligible for study were diffuse large B-cell lymphoma (DLCL), peripheral T-cell lymphoma (PTCL), follicular lymphoma grade 3 (FL gr3), anaplastic large cell lymphoma (ALCL), and indolent lymphomas with aggressive transformation (TL). Patients were treated with standard dose CHOP that included SV 2.0 mg/m2 without dose capping, ± rituximab 375 mg/m2, given every 21 days for 6 to 8 courses (ASH abst. 338, 2002). Results: Of 73 patients enrolled on study, 68 were evaluable for response. Median age was 61 (range 22–80), 36 patients (53%) were >60 years old. Overall, 24 patients (23 elderly) had an IPI score ≥3. Patients received a median of 6 study treatments (range 1–8). Diagnoses were: DLCL = 56; FL gr 3 = 4; PTCL = 4; ALCL = 2 and TL = 2. ORR was 92.6% (63/68 pts) with 55 pts achieving CR (80.1%), 7 CRu (10.3%), and 1 PR (1.5%); 3 patients had PD (4.4%) and 2 were not assessed for response (2.9%). ORR was similar in both elderly (>60) and younger pts (≤60): 91.9% and 93.5% respectively. Neuropathy was generally mild (Gr.1–2). Hematological toxicities were as follows: 56% Gr.3–4 neutropenia, 6% Gr.3 anemia, and 13% Gr.3–4 thrombocytopenia. Toxicites were comparable in elderly and younger patients. The median follow up for the study is 39.6 months (mos), and overall survival 94%. There have been 9 relapses (5 DLCL, 3 T-cell, 1 FL gr3, 1 transformed) for elderly patients and 5 relapses (4 DLCL, 1 T-cell) for patients ≤60. The table below shows progression free survival (PFS) at 3 years, for all histologies, and DLCL by age. There is no difference between the age groups. Conclusions: This regimen, with sphingosomal vincristine in CHOP +/− Rituximab, has a high overall response rate. It is a well-tolerated therapy with mild neurotoxicity for all patients. At 3 years, the PFS in elderly patients with DLCL treated with RCHOP is comparable to that of younger patients, despite a larger fraction of high risk IPI in the older patients. This regimen merits randomized comparison to RCHOP in DLCL. Age (Yrs) All Histologies (n=68) DLCL (n=56) ≤60 84%, CI [66–93] 85%, CI [66–94] >60 83%, CI [66–92] 86%, CI [66–94]

Long-Term Follow-Up of a Phase II Trial of Six Cycles of Dose-Dense R-CHOP-14 for First-Line Treatment of Diffuse Large B-Cell Lymphoma in Young and Elderly Patients

2016 ◽  
Vol 136 (2) ◽  
pp. 76-84 ◽  
Author(s):  
Eva González-Barca ◽  
Miguel A. Canales ◽  
Antonio Salar ◽  
Secundino Ferrer ◽  
Eva Domingo-Domenech ◽  
...  
Keyword(s):  
Survival Rate ◽  
Elderly Patients ◽  
B Cell ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
International Prognostic Index ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background/Aims: Rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 14 days seems to achieve better outcomes than R-CHOP every 21 days in diffuse large B-cell lymphoma (DLBCL) patients. Currently, the standard regimen is R-CHOP every 21 days. Methods: This is a phase II clinical trial of treatment with 6 cycles of R-CHOP-14 with pegfilgrastim support in 2 populations of previously untreated DLBCL patients aged ≥65 years (n = 73) or <65 years (n = 51) with low-risk International Prognostic Index scores (0-2). Results: With a median follow-up of 63.7 months, the 5-year event-free survival rate was 53.8% in patients aged ≥65 years and 71.0% in patients aged <65 years. The 5-year overall survival rate was 71.4 and 89.8%, respectively. The complete remission rate was 69.9% for older and 80.4% for younger patients. The median relative dose intensity of cytotoxic drugs was 143.2% in the elderly and 149.1% in the young patients. Febrile neutropenia was the most common grade 3-4 adverse event, being higher in elderly patients (21.3 vs. 9.3%). Eight deaths (7 in elderly patients) were considered treatment related. Conclusion: In conclusion, the R-CHOP-14 regimen is feasible and very active, though it is more toxic in elderly patients mainly due to an increased incidence of infections. New strategies, such as new monoclonal antibodies or new targeted therapies, are needed to improve the outcomes of DLBCL patients.

VNCOP-B (Etoposide, Mitoxantrone, Cyclophosphamide, Vincristine, Prednisolone, Bleomycin) Plus Rituximab Therapy in Elderly Patients with Aggressive B-Cell Non-Hodgkin Lymphoma: A Phase II Study of Efficacy and Safety

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3586-3586
Author(s):  
Kazuyoshi Ishii ◽  
Masahiro Manabe ◽  
Toshiya Yagi ◽  
Hirofumi Teshima ◽  
Yasuaki Nagare ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Phase Ii ◽  
Induction Therapy ◽  
Phase Ii Study ◽  
B Cell Lymphoma ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Grade 3

Abstract [Background and Objectives] CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) plus rituximab is a standard chemotherapy used to treat patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). However, among elderly patients, this regimen has not been completely satisfactory in its efficacy and safety because of agespecific comorbidity, increased toxicities of chemo-agents, and the more aggressive aspect of the lymphoma itself. Zinzani reported that a combination therapy including etoposide, mitoxantrone, cyclophosphamide, vincristine, prednisolone, and bleomycin (VNCOP-B) was effective in elderly aggressive NHL patients (Blood1999;94:33–38). We conducted a phase II multicenter study in 8 collaborative institutions to determine if VNCOP-B plus rituximab was effective and safe to treat elderly patients with aggressive B-NHL. The primary endpoint was to detect overall survival (OS). The second endpoint was to detect the response rate (RR) and progression-free survival (PFS). [Patients and Treatment] Eligible patients were those aged over 60 years, with aggressive B-NHL documented as CD20 surface antigen positive, performance status (PS) 0 to 2, clinical stage over II or I with a bulky disease, measurable lesions, no prior chemotherapy nor radiation, no severe complications, no major organ dysfunction, no other active cancer, not a HBV carrier, no central nervous system involvement with lymphoma, and who gave the required written informed consent. VNCOP-B plus rituximab was administered as an induction therapy. This protocol was completed in 8 weeks and consisted of weekly doses of chemotherapy combined with rituximab every two weeks. During the 8 weeks of therapy, granulocyte colony-stimulating factor (G-CSF) was administered on a prophylactic base. Rituximab was administered weekly four times a month as a sequential therapy, following one month after the end of the induction therapy. [Results] Between September 2004 and December 2007, 23 patients, median age 73 years, 50.0% classified as high-intermediate/high risk on the age-adjusted International Prognostic Index (IPI), entered this trial and 21 were evaluated for feasibility, toxicity, and efficacy. Twenty-two patients (95.2%) were diagnosed with diffuse large B-cell lymphoma and one (4.8%) with mediastinal large B-cell lymphoma. The nineteen patients (90.5%) completed the induction therapy and all these then received a sequential rituximab therapy. Complete remission rate was 90.5%, with a 100% overall RR at the end of induction therapy; OS rate at 3 years was 76.4% (median follow-up 744days); with an 82.6% 3-year PFS rate (median follow-up 744days). Average Relative dose intensity (RDI) in MIT was 0.61, no significant difference in survival was found regarding RDI. Although IgG level decreased during the induction therapy, it recovered to the prior level after sequential rituximab (IgG means±standard error: pre-treatment 1355.2±146.4mg/dl, post-induction therapy 785.3±107.0mg/dl, post-sequential rituximab 1010.4±60.2mg/dl). According to the IPI, there was a trend suggesting a lower probability of OS and PFS in high/high-intermediate risk than in low/low-intermediate risk cases (3-year OS: 67.5% versus 100.0%, P=0.51; 3-year PFS: 66.7% versus 100.0%, P NA). The most common grade 3/4 toxicities were hematologic, including neutropenia in 75.0% of the 21 patients despite prophylactic administration of G-CSF, febrile neutropenia in 30.0%, and thrombocytopenia in 10.0%, respectively. Regarding non-hematologic grade 3/4 toxicities, hepatitis occurred in one patient (5.0%) from HCV reactivation, intestinal perforation involving the lymphoma in one patient (5.0%). There was no treatment-related mortality. We had conducted a phase II study of VNCOP-B therapy in 16 elderly patients with aggressive B-NHL (Gan To Kagaku Ryoho2005;32:39–44, in Japanese). Against this historical comparison, the present protocol seemed better in PFS than that without rituximab (3-year PFS: 82.6% versus 56.0%, P=0.11), although OS was almost the same (3-year OS: 76.4% versus 73.4%, P=0.22). [Conclusion] Although our enrolled patients were quite elderly with a median age of 73 years, and half of them had a poor prognosis index, VNCOP-B combined with rituximab was well tolerated and showed promise.

scholarly journals Rituximab-CHOP and Central Nervous System Prophylaxis Using Intrathecal Methotrexate in Primary Breast Diffuse Large B-Cell Lymphoma: A Prospective, Multicenter, Single-Arm Phase II Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4076-4076
Author(s):  
Ho-Young Yhim ◽  
Cheolwon Suh ◽  
Seok Jin Kim ◽  
Deok-Hwan Yang ◽  
Hyeon-Seok Eom ◽  
...  
Keyword(s):  
Phase Ii ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Intrathecal Methotrexate ◽  
Cns Prophylaxis ◽  
Large B Cell Lymphoma

Background: Primary breast diffuse large B-cell lymphoma (DLBCL) has poor outcomes with frequent extranodal failures, particularly in the central nervous system (CNS). To prevent CNS recurrence, we designed this phase II trial that addressed feasibility and activity of conventional immunochemotherapy and CNS prophylaxis. Methods: This prospective, multicenter, single-arm phase II study was conducted to evaluate efficacy and safety of 6 cycles of conventional rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone every 21 days (R-CHOP) with the addition of 4 doses of intrathecal methotrexate (IT MTX; 12mg) during the first 4 cycles of R-CHOP in patients with primary breast DLBCL. Primary breast lymphoma was defined as lymphoma involving one or both breasts as a sole extranodal site regardless of specific nodal involvement status. The primary end-point was 2-year progression-free survival (PFS). Secondary end-points included cumulative incidence of CNS recurrence, overall survival (OS), and safety. All patients provided written informed consents and the study was registered at www.clinicaltrials.gov as #NCT01448096. Results: Thirty-three patients with primary breast DLBCL were enrolled between Jan 2012 and Jul 2017 in the Consortium for Improving Survival of Lymphoma (CISL) member institutions. The median age was 50 years at diagnosis (range, 29-75) and all were female. Right breast involvement was more common than left (18 [55%] vs 14 [42%]) and bilateral breast involvement was found in one patient (3%). Nodal involvement was present in 16 patients (49%), primarily in regional nodes (14 patients). Thus, the Ann Arbor stage was IE in 17 (52%), IIE in 13 (39%), IIIE in 2 (6.1%), and IV in 1 (3.0%). ECOG performance status was ≥2 in 1 patient (3%) and serum LDH level was elevated in 9 (27%). Therefore, the IPI and the CNS-IPI risk were mainly low (28 patients, 85%; respectively). No patients had CNS involvement at diagnosis. 32 (97%) of the 33 patients completed R-CHOP as planned, and the remaining patient withdraw a consent after four cycles of R-CHOP because of poor tolerance. CNS prophylaxis using IT MTX was completed as planned in 31 patients (94%), but it was discontinued in 2 patients because of patient's refusal. These 2 patients received two and three IT MTX doses, respectively. 32 patients (97%) were evaluable for treatment response and all these patients achieved a complete response. At the cutoff date of this analysis (10 Jul 2019), all patients who entered a follow-up phase had at least 24.0 months of follow-up. With a median follow-up duration of 46.1 months (IQR 31.1-66.8), 6 patients had experienced treatment failure and 3 of these died. The 2-year PFS and OS were 81.3% (95% CI, 67.7-94.8) and 93.5% (95% CI, 84.9-100.0), respectively (fig 1A and B). Of the 6 patients with treatment failure, diseases involved CNS with or without lymph nodes in 4 patients and breasts in 2 patients (1 ipsilateral and 1 contralateral breast recurrence). 3 of the four patients with CNS recurrence had isolated CNS recurrences (2 brain parenchymal and 1 meningeal disease) and one had a concurrent meningeal and lymph nodal recurrence. All 4 patients with CNS recurrence had received prophylactic IT MTX as planned by protocol. The 2-year cumulative incidence of CNS recurrence, taking into account the competing risk of death, was 12.5% (95% CI, 0.3-23.2, fig 1C). Although the number of patients with intermediate CNS-IPI risk was small (5 patients, 15%), the cumulative incidence of CNS recurrence did not differ significantly according to the CNS-IPI risk group. All CNS recurrences occurred within the first 2 years after enrolment. Toxicities were generally manageable during the R-CHOP and IT MTX treatment. No deaths as a result of toxicity occurred during treatment. Conclusion: Our study shows that conventional R-CHOP with prophylactic IT MTX is feasible in patients with primary breast DLBCL. However, given a substantially high rate of CNS recurrence, further studies to properly define the best strategy for CNS prophylaxis should be needed in patients with primary breast DLBCL. Figure 1 Disclosures Yoon: F. Hoffmann-La Roche Ltd: Research Funding. Kim:Celltrion: Research Funding; Novartis: Research Funding; Donga: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J + J: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding.

CALGB 59901: Results of a Phase II Study of 506U78 in CTCL and PTCL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2486-2486 ◽  
Author(s):  
Myron S. Czuczman ◽  
Pierluigi Porcu ◽  
Jeff Johnson ◽  
Donna Niedzwiecki ◽  
George P. Canellos ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Western Hemisphere ◽  
Water Soluble ◽  
T Cell Lymphoma ◽  
Grade 3

Abstract T-cell lymphoma comprises approximately 10% to 15% of all lymphomas seen in the Western hemisphere and may be broadly categorized into 2 main groups: the various histologies of peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL). Overall, PTCL patients (pts) are believed to have a worse prognosis than pts with B-cell lymphoma. Except for the favorable subset of ALK-1-positive anaplastic large cell lymphoma, most PTCL are incurable with standard therapy. Salvage chemotherapy is often ineffective in relapsed PTCL or in pts with advanced CTCL no longer responding to agents that modulate T-cell function (e.g. retinoids, interferons, antibodies). New agents are needed for these pts. 506U78 is a pro-drug of ara-G, a deoxyguanosine analogue. Ara-G itself is difficult to synthesize and poorly water soluble. 506U78 is 10 X more water soluble than ara-G and is rapidly demethoxylated in blood to ara-G, which has been shown to be toxic to T-cells at even micromolar concentrations. Based on positive preliminary data with 506U78 in pediatric pts with recurrent/refractory precursor T-lymphoblastic lymphoma or leukemia (PTLL), we activated CALGB protocol 59901, a Phase II study of 506U78 in pts with systemically untreated CTCL or refractory/relapsed PTCL. Objectives were to determine response rate, remission duration, and safety associated with 506U78 given at 1.5 g/m2/day on Days 1, 3, and 5 as an IV infusion q 21 days for a minimum of 2 cycles and/or to continue for 2 cycles after CR (up to max of 8 cycles). Eligibility included: diagnosis of PTCL or CTCL; measurable disease; no CNS lymphoma; no history of seizure disorder or significant (>grade 1) neurologic dysfunction; age <70; PS 0–2; adequate renal and hepatic function; CTCL pts were originally not permitted to have received systemic chemo, but the protocol was amended on 2/15/02 to allow therapy with one prior course of single-agent chemotherapy in an attempt to increase accrual. Nineteen pts were enrolled between 5-15-00 and 3-15-04: 11 CTCL and 8 PTCL pts. Five of 11 CTCL pts had received no prior therapy and 7 of 7 evaluable PTCL pts had received prior chemo and 2 prior BMT. Adverse event (AE) data are available for 18 pts. Grade 3 or 4 AEs were documented in 50% and 28% of pts, respectively. Thirty-three percent of pts experienced Grade 3 or 4 neurologic toxicities which included: ataxia, vertigo, peripheral neuropathy, confusion, and/or depressed consciousness. There were 2 treatment-related deaths, 1 due to infection and 1 due to CNS hemorrhage (both in pts with CTCL). There were 2 PRs to therapy, one each in the PTCL and CTCL groups, with disease progression at 3m and 5.5m, respectively. The overall response rate is 10.5% (1.3% – 33.1%; 95% CI). Fifteen of 19 pts have died. Median EFS was 1.2m (1.0, 1.6 m; 95% CI) and median OS was 3 months (1.4, 9.8m; 95% CI). Due to lack of efficacy and excessive toxicity the protocol was closed on 3/15/04. In contrast to the favorable results seen in pediatric pts with recurrent PTLL, our data demonstrate that 506U78 has low efficacy, is unacceptably toxic and is not recommended as monotherapy in adult pts with CTCL and PTCL.

scholarly journals Safety of chidamide plus rituximab in elderly patients with relapsed or refractory B-cell lymphoma in China: a multicenter, single-arm, phase II study

2021 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
Xinrui Chen ◽  
Huaqing Wang ◽  
Xiuhua Sun ◽  
Liping Su ◽  
Fengting Liu ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
B Cell Lymphoma
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