Final results of phase I/II trial of vorinostat in combination with cyclophosphamide, etoposide, prednisone, and rituximab (R-CVEP) for elderly patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8054-8054 ◽  
Author(s):  
David J. Straus ◽  
Paul A. Hamlin ◽  
Matthew J. Matasar ◽  
Maria Lia Palomba ◽  
Pamela Drullinsky ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Phase I ◽  
B Cell ◽  
Phase Ii ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Maximum Tolerated Dose ◽  
Combination Methods ◽  
Positron Emission

8054 Background: Standard treatment of relapsed/refractory DLBCL in elderly patients who are not candidates for autologous stem cell transplantation (auSCT) has not been established. Cyclophosphamide (C), etoposide (E), prednisone (P) and procarbazine (CEPP) has been used by many clinicians based on limited data (Blood 76: 1293-98, 1990). Vorinostat (V) is a histone deacetylase inhibitor that is approved for relapsed cutaneous T-cell lymphoma and has activity in B-cell lymphomas. This trial defined the maximum tolerated dose (MTD) of V added to standard therapy and determined the response rate of this combination. Methods: Patients ≥age 60 with relapsed/refractory DLBCL not candidates for auSCT were enrolled on R-CVEP (R 375mg/m2 IV, d1; C 600mg/m2 d1 and 8, E 70mg/m2 IV d1, 140mg/m2 d2 and 3; V PO and Pred 60mg/m2 PO d1-10) every 28 days for 6 cycles. In the phase I component V was administered at doses of 300mg/d or 400mg/d for 10 days. The phase I was a 3 + 3 design and the phase II a two stage design requiring 8/20 complete responses (CR) for expansion. Assessment of response utilized end-of-treatment positron emission tomography (PET) (JCO 25: 579-86, 2007). Quality of life (QOL) was measured with the FACT-Lym v.4. Results: 27 pts. were enrolled. 1 died before treatment. For 26 pts: median age 76 yrs. (69-88), 14 females and 12 males, baseline PS (ECOG) 1 (0-2). Median follow-up for survivors: 9.2 mo. Phase I: 6 pts. at 300mg/d (no dose-limiting toxicity-DLT), 6 pts. at 400mg/d (2 grade 3 neutropenia = DLT). MTD 300mg/d x 10d. For 20 pts. at V 300mg/m2 (6 phase I + 14 phase II): 2 off study for toxicity, 1 withdrew consent, 6 CR (30%), 5 partial response (PR) (25%), 6 progressed (30%). Phenotypic overall responses (OR): germinal center (GC) 4/8 (2 CR), non-GC 6/10 (3 CR), transformed CLL 1/2 (1 CR). Median progression-free survival: 10 mo. QOL results will be presented. Conclusions: OR rate for V added to conventional chemotherapy and R was 55% (CR 30%, PR 25%) in relapsed/refractory DLBCL in elderly pts. not candidates for auSCT. This could provide a baseline for comparison with future clinical trials in this understudied population.

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.

scholarly journals Age-dependent increase of treatment-related mortality in older patients with aggressive B cell lymphoma: analysis of outcome, treatment feasibility, and toxicity in 1171 elderly patients with aggressive B cell lymphoma—data from phase II and III trials of the DSHNHL (German High-Grade Non-Hodgkin’s Lymphoma Study Group)

2020 ◽  
Author(s):  
Florian Zettl ◽  
Marita Ziepert ◽  
Bettina Altmann ◽  
Samira Zeynalova ◽  
Gerhard Held ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Patient Population ◽  
Cell Lymphoma ◽  
Age Groups ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Age Dependent ◽  
Aggressive B Cell Lymphoma

AbstractIn elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61–65 years, 66–70 years, 71–75 years, and 76–80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76–80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.

Phase I Trial of Bortezomib (NSC 681239) and Flavopiridol (NSC 649890) in Patients with Recurrent or Refractory Indolent B-Cell Neoplasms.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3338-3338 ◽  
Author(s):  
Steven Grant ◽  
Daniel Sullivan ◽  
David Roodman ◽  
Robert Stuart ◽  
Edward B. Perkins ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Phase Ii ◽  
Phase I Trial ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Human Leukemia ◽  
Related Disorder ◽  
Nf Kappab ◽  
Dose Levels

Abstract Preclinical studies suggest that neoplastic cells may be particularly sensitive to simultaneous interruption of cell-cycle and survival signaling pathways. In accord with this concept, we have shown that flavopiridol (F), a CDK inhibitor, interacts with Bortezomib (B), a proteasome inhibitor, to induce mitochondrial injury and apoptosis in human leukemia, myeloma, and lymphoma cells (Dai et al, Oncogene22:7108, 2003; Dai et al, Blood104,509,2004). These actions were associated with inhibition of NF-kappaB DNA binding, and diminished expression of phospho-JNK, XIAP, and Mcl-1. Based on these findings, we have initiated a phase I trial to identify appropriate doses of B+F for further investigation. Eligible patients (pts) include those with multiple myeloma, indolent B-cell lymphoma, or a related disorder, and must have recurrent or refractory disease following at least 1 prior systemic therapy (excluding allogeneic stem cell transplantation). Pts receive B (iv bolus) immediately followed by F (1 hour infusion) on days 1, 4, 8, and 11; courses are repeated every 21 days. Targeted dose levels are (B/F; mg/m2): 1.0/15, 1.3/15, 1.3/22, 1.3/30, and 1.3/40. Dose limiting toxicity (DLT) is defined as NCI CTCAE grade 4 ANC/platelet for &gt; 1 week or grade ≥ 3 non-heme toxicity. 14 pts have been treated at 4 dose levels. There have been no DLT to date. There have been 3 episodes of herpes zoster (2 disseminated), 4 cases of exacerbation of pre-existing peripheral neuropathy, and 8 pts have discontinued study treatment after 1 to 5 cycles due to non-DLT toxicities. Among 11 patients evaluable for response and who are Bortezomib-naive, there has been 1 complete response (mantle cell lymphoma; MCL), 3 partial responses (2 myeloma, 1 lymphoma), and 5 patients with stable disease (3 myeloma, 1 lymphoma, 1 Waldenstrom’s). The patient with MCL who achieved a CR had previously received CHOP, Rituximab-CHOP, and fludarabine-Rituximab x 2. Correlative laboratory studies involving bone marrow CD138+ cells from patients with myeloma revealed a reduction in post-treatment NF-kappaB nuclear localization in 4/5 evaulable patients. Variable effects on myeloma cell expression of phospho-JNK, Mcl-1, and XIAP have been observed. Additional patients who previously received Bortezomib have now been entered on the study, but it is too early to evaluate their responses. Collectively, these findings indicate that a regimen combining Bortezomib and flavopiridol is well tolerated in patients with progressive B-cell malignancies, and has clear activity in some patients refractory to standard therapy. Pending identification of the MTD and RPTD (recommended phase II dose), Phase II evaluation of this therapeutic strategy should define its activity more definitively.

scholarly journals Phase I Multidose-Escalation Study of the Anti-CD19 Maytansinoid Immunoconjugate SAR3419 Administered by Intravenous Infusion Every 3 Weeks to Patients With Relapsed/Refractory B-Cell Lymphoma

2012 ◽  
Vol 30 (22) ◽  
pp. 2776-2782 ◽  
Author(s):  
Anas Younes ◽  
Stella Kim ◽  
Jorge Romaguera ◽  
Amanda Copeland ◽  
Silvana de Castro Farial ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Intravenous Infusion ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Pharmacokinetic Profile ◽  
Maximum Tolerated Dose ◽  
Clinical Activity ◽  
Antibody Drug Conjugate ◽  
Blurred Vision

Purpose We determine the maximum-tolerated dose (MTD), pharmacokinetics, safety, and preliminary efficacy of SAR3419, an antibody-drug conjugate targeting CD19, in a first-in-man phase I clinical trial in patients with relapsed lymphoma. Patients and Methods Patients with relapsed CD19+ B-cell lymphoma were treated with escalating doses of SAR3419 given by intravenous infusion once every 21 days. Results Thirty-nine patients were treated on seven dose levels ranging from 10 to 270 mg/m2. The median number of prior treatment regimens was four (range, 1 to 9), and 11 patients had prior autologous or allogeneic stem-cell transplantation. The dose-limiting toxicities were reversible severe blurred vision associated with microcystic epithelial corneal changes reported in six patients and neuropathy in one patient. The MTD was 160 mg/m2 once every 21 days. Hematologic and hepatic toxicities were predominantly grade 1 or 2 in severity. A total of 35 patients have completed at least two cycles of treatment and were evaluable for tumor response. Twenty-six patients (74%) demonstrated reduction in their tumor size; six of those patients achieved partial or complete remissions. Seven (47%) of 15 patients with rituximab-refractory disease demonstrated reduction in their tumor sizes. The pharmacokinetic profile of SAR3419 is characterized by linear kinetics, low clearance from 0.2 to 0.6 L/d/m2, and an elimination half-life in the range of 3 to 7 days. Conclusion Using an every 3-week-schedule of SAR3419 for six cycles, the MTD is 160 mg/m2. SAR3419 can be safely administered to patients with relapsed B-cell lymphoma and demonstrates promising clinical activity, including patients who were refractory to rituximab.

Sign in / Sign up

Export Citation Format

Share Document