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Background: The objective of ECOG 1503 was to determine the response rate of this combination in the second-line treatment of advanced NSCLC. Methods: Triapine 105 mg/m2 IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15, of a 28 day cycle. Results: Eighteen patients enrolled. Three patients were not eligible due to protocol violations. No objective antitumor responses were seen. Three patients (20%) experienced stable disease (90% CI 5.7–44%). Median overall survival: 5.4 months (95% CI 4.2–11.6 months); median time to progression: 1.8 months (95% CI 1.7–3.5 months). Five patients developed acute infusion reactions to Triapine® related to elevated methemoglobinemia. Patients with MDR1 variant genotypes of C3435T experienced superior overall survival compared to non-variants (13.3 vs. 4.3 months, respectively, p = 0.023). Conclusion: This regimen did not demonstrate activity in relapsed NSCLC. Prolonged survival seen with MDR1 variant genotypes is hypothesis-generating.

Abstract 3647 Introduction: BR chemoimmunotherapy was shown to have an overall response rate (ORR) of 59%, a median progression-free survival (PFS) of 14.7 months, and an acceptable toxicity profile in R/R CLL (Fischer K, et al. J Clin Oncol 2011). Given the single-agent activity of lenalidomide in R/R CLL/SLL, we hypothesized that maintenance lenalidomide after BR induction could improve PFS. Methods: Thirty-four patients requiring therapy for R/R CLL/SLL were treated with bendamustine 90 mg/m2 IV on days 1 & 2 and rituximab 375 mg/m2 IV on day 1 every 28 days for a maximum of 6 cycles. Growth factor support was permitted. Patients achieving at least a minor response (objective improvement even if not meeting criteria for partial response) were eligible to proceed with 12 cycles of maintenance therapy with lenalidomide 5–10 mg/day orally given continuously in each 28-day cycle. Patients were eligible if they had histologically proven CLL/SLL and had received >1 but ≤5 prior cytotoxic chemotherapy regimens (retreatment with an identical regimen was not counted as a separate treatment). The primary endpoint was PFS. Results: Baseline characteristics include median age 67 (range 38–86), 25 men/9 women, 26 CLL/8 SLL, and median of 2 prior therapies (range 1–4). Cytogenetic profiling by FISH analysis was available in 22 patients (65%), with 11/22 demonstrating presence of 17p and/or 11q deletions. Twenty-five patients (74%) completed 6 cycles of induction BR. Two patients died from toxicities of pneumonia and heart failure during cycle 1; 7 patients received Conclusions: In our multicenter trial for patients with R/R CLL/SLL, the BR induction produced an ORR that is comparable to historical observations (65% vs 59%). However, the median PFS is longer (24.3 vs 14.7 months), suggesting maintenance lenalidomide may be contributing to an improved response duration. Based upon these promising results, we have initiated a successor study in which patients will receive lenalidomide plus rituximab maintenance after a BR induction. Disclosures: Chang: Celgene: Research Funding; Genentech: Research Funding. Off Label Use: Lenalidomide as maintenance therapy for CLL after induction rituximab + bendamustine chemoimmunotherapy. Fenske:Spectrum Pharmaceuticals: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Kahl:Millennium: Consultancy, Research Funding; Roche: Consultancy; Genentech: Consultancy, Research Funding.

Introduction: Mantle cell lymphoma has the poorest 5-year survival of all the non-Hodgkin’s lymphoma subtypes and appears incurable with standard therapies. High response rates are seen with CHOP plus rituximab (R), but the progression free survival (PFS) is disappointingly short (median 16–20 months). Favorable results have been reported for hyper-CVAD + R with midcycle high dose methotrexate and cytarabine, but this regimen can be prohibitively toxic for some patients. We hypothesized that eliminating methotrexate and cytarabine while adding R to the induction hyper-CVAD would produce high response rates with acceptable toxicity. We further hypothesized that adding R maintenance would prolong the PFS. Methods: Eligible patients had histologically confirmed CD20+ mantle cell lymphoma and could not have received more than 1 cycle of CHOP-like therapy for their disease prior to study entry. PS 0-2 was allowed. The treatment plan included rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1–3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1–2, vincristine 2 mg IV day 3, dexamethasone 40 mg po days 1–4, and G-CSF 5mg/kg/day starting after therapy until ANC ≥ 4000/mm3. Cycles were repeated every 28 days, up to 6 cycles. Patients achieving at least a PR received R maintenance therapy (375 mg/m2 IV weekly X 4 doses) every 6 months for 2 years. The accrual goal was 20 patients evaluable for response. Results: Enrollment is completed. All 22 patients are evaluable for toxicity, PFS, and OS and 20 patients evaluable for response rate (2 patients died before any restaging). Patient characteristics include 20/22 male, median age 63 (40–81), median IPI 3 (1–5), and 19/22 stage IV. All patients have completed the induction chemotherapy. Six patients have completed the R maintenance, 10 remain on R maintenance, and 6 patients came off study due to progressive disease (4) or death (2). The ORR is 85% (17/20) with 3 PR, 14 CR/CRu. With a median follow up of 22.5 months (range 4–45), the median PFS and OS have not been reached. The 2-year PFS is 73% (95% CI 50–89%) and the 2-year OS is 82% (95% CI 60–95%). Responses are ongoing in 16 patients, with response duration ranging from 2+ to 39+ months. The most common grade 3–4 toxicities in the 22 patients included neutropenia (10), anemia (5), thrombocytopenia (5), and infection (4). To date, five patients who participated in this study have died (1 treatment-related neutropenic fever, 1 post-surgical infection, 3 progressive disease). The major toxicity of this treatment regimen is expected hematologic toxicity. Conclusion: Modified hyper-CVAD with rituximab maintenance demonstrates ORR comparable to conventional hyper-CVAD (85% vs. 93%) and is less toxic, especially in patients over 60. Compared with published reports for R-CHOP, we observed higher CR rates (70% vs 34–48%) and considerably longer median PFS (not yet reached vs. 16–20 months). Longer follow up will better define the effectiveness of this regimen, but the encouraging results of this pilot study provide the basis for additional study in a larger setting.

Twelve patients receiving heparin during hemodialysis had coagulation parameters monitored using the whole blood clotting time (WBCT), activated partial thromboplastin time (APTT), plasma heparin levels and activated whole blood clotting time (AWBCT). The AWBCT, performed with a battery-powered portable incubator/timer, correlated with both the corresponding WBCT and the plasma heparin levels. However, the correlation between the AWBCT and the APTT was quite poor. This assay is simply performed, inexpensive, and reproducible. It is recommended as an excellent method for monitoring heparin therapy.