Phase I Trial of Toll-Like Receptor 9 Agonist PF-3512676 with and Following Rituximab in Patients with Recurrent Indolent and Aggressive Non–Hodgkin's Lymphoma

2007 ◽  
Vol 13 (20) ◽  
pp. 6168-6174 ◽  
Author(s):  
John P. Leonard ◽  
Brian K. Link ◽  
Christos Emmanouilides ◽  
Stephanie A. Gregory ◽  
Daniel Weisdorf ◽  
...  
Keyword(s):  
Phase I ◽  
Hodgkin’S Lymphoma ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Toll Like Receptor ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Phase I trial of combination therapy with 90Y ibritumomab tiuxetan and gemcitabine in patients with non-Hodgkin’s lymphoma

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17514-17514
Author(s):  
H. Borghaei ◽  
M. Smith ◽  
M. Millenson ◽  
K. Krieger ◽  
A. Rogatko ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Hematologic Toxicity ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Grade 3

17514 Background: Zevalin (Z) is an effective therapy in patients with relapsed or refractory low grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). Gemcitabine (gem) also is active against NHL and is a potent radiation sensitizer. We are conducting a phase I trial to assess the safety of concomitant administration of Z and gem in patients with NHL. Methods: The starting gem dose is 250 mg/m2 on days 1 and 8. Nine patients in three cohorts will be treated with 250 mg/m2 of gem with 0.2, 0.3 or 0.4 mCi/kg of Z. The next cohort can accrue after all patients in the prior cohort have hematologic toxicity has recovered to grade 2 or after 60 days from the date of the last treated patient in the previous cohort. Once it is confirmed that a Z dose of 0.4 mg/kg can be safely administered with gem 250 mg/m2, gem will be escalated according to a Bayesian based system. Response evaluation is based on the International Workshop on Standardized Response Criteria for Non-Hodgkin’s lymphomas. Eligibility criteria include: any histology of recurrent NHL (not candidates for high dose therapy), platelets ≥ 150,000/ul; < 25% bone marrow involvement by lymphoma; prior radiation to < 25% radiation of bone marrow and no prior bone marrow or stem cell transplant. Results: Five patients have been treated thus far, two with follicular NHL (FL) and three with diffuse large B cell (DLBCL). Median age is 75 (range 55–82). The median number of prior treatments is 2 (range 1–6). One patient with DLBCL is not evaluable. The first three patients received 0.2 mCi/kg and next two patients 0.3 mCi/kg of Zevalin. Toxicity consists of grades 2 & 3 myelosuppression in the first 3 weeks in 3 pts. due to gem and then of grade 2 in 1 pt. at 6 to 8 weeks as is usually seen with Z. One grade 3 leukopenia and one grade 2 thrombocytopenia have been observed resolving within one week. One grade 3 infection occurred, unrelated to the protocol or the study drugs. No grade 3 or 4 non-hematologic toxicity has been seen. In follow up, two patients with FL and one with DLBCL achieved CRu. One patient with DLBCL has progressed and one is not yet evaluable. Conclusions: Our preliminary findings suggest that Z can be safely combined with gem 250 mg/m2 in the treatment of patients with NHL. Dose escalation to full dose Zevalin and then of gemcitabine is continuing. [Table: see text]

Phase I Trial of Fludarabine and Paclitaxel in Non-Hodgkin's Lymphoma

2003 ◽  
Vol 20 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Muhammad R. Abbasi ◽  
Joseph A. Sparano ◽  
Catherine Sarta ◽  
Peter H. Wiernik
Keyword(s):  
Phase I ◽  
Hodgkin’S Lymphoma ◽  
Phase I Trial ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

A phase I trial evaluating the safety and biological activity of iboctadekin (rhIL-18) in combination with rituximab in patients with CD20+ B-cell non-Hodgkin's lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8566-8566 ◽  
Author(s):  
M. J. Robertson ◽  
J. Kline ◽  
J. Bauman ◽  
O. Gardner ◽  
Z. Jonak ◽  
...  
Keyword(s):  
Biological Activity ◽  
Phase I ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Activation Markers ◽  
Immune Modulators ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Tumor Activity

8566 Background: Iboctadekin (rhIL-18) is an immunostimulatory cytokine that has demonstrated anti-tumor activity in several preclinical models. When administered as monotherapy in phase I clinical studies, rhIL-18 was safe, well tolerated and induced potent biological responses (e.g. Th1 cytokine production and expression of activation markers on NK, CD8+ and CD4+ cells). These data affirm the endogenous role of IL-18 as a co-stimulatory cytokine and suggest that its optimal use would be in a combination with other immune modulators such as rituximab. Methods: Patients with CD20+ B cell non-Hodgkin's lymphoma are being given rituximab (375 mg/m2) IV weekly for 4 consecutive weeks in combination with ascending doses of intravenous rhIL-18 (1 to 100 mcg/kg in 6 cohorts of 3 patients each) IV weekly for 12 weeks to identify a dose that is safe and tolerable and gives a maximum biological effect. Eligible patients must have disease which progressed after standard therapy or for which there is no effective standard treatment. Assessments include safety/tolerability, pharmacokinetics, pharmacodynamics (serum cytokines, peripheral blood phenotypic markers and tumor biomarkers), immunogenicity and anti-tumor activity. Results: To date, thirteen subjects have been enrolled in the first four cohorts (1, 3, 10 and 20 mcg /kg of rhIL-18). The combination is well tolerated with a safety profile similar to that observed with rituximab or rhIL-18 monotherapy. The pharmacodynamic response is as expected with a dose-dependent decrease in circulating activated (CD69+) NK cells within 4 hours after completing the rhIL-18 infusion which rebound to pre-dose levels within 2–4 days. Using the International Working Group response criteria for lymphoma, two subjects had complete responses at 10 and 20 mcg/kg, one subject had a partial response at 10 mcg/kg and three subjects had stable disease at 1, 3 and 3 mcg/kg. Conclusions: These data show that the combination of rhIL-18 and rituximab is safe, well tolerated and induces potent biological activity. This study will define the dose level to be used in a future phase II trial evaluating this combination in patients with relapsed or refractory follicular lymphoma. [Table: see text]

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