ALBERT

Description: Introduction: Rituximab and bendamustine combination regimens have demonstrated high activity in non-Hodgkin's lymphoma (NHL). Phase III trials evaluating bendamustine plus rituximab as first-line therapy for patients (pts) with indolent and mantle cell lymphoma have shown equivalent or superior results when compared to R-CHOP or R-CVP as first-line treatment for indolent lymphoma. The proteasome inhibitor, bortezomib, has shown substantial activity in multiple myeloma and has demonstrated synergy and/or ability to overcome resistance to a variety of current and investigational treatments for lymphoma. A Phase II study of the combination of bendamustine, bortezomib, and rituximab (BBR) in relapse/refractory indolent and mantel cell NHL pts resulted in an ORR of 83% and 47% 2yr PFS (Friedberg, Blood 2011). This Phase II trial evaluated the activity of BBR in patients with previously untreated low-grade lymphoma. Methods: Eligible patients had histologically-confirmed follicular center cell lymphoma (FL) (grade 1 or 2), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), or lymphoplasmacytic lymphoma (LPL); lymph node biopsy containing CD20+ B-cells; Ann-Arbor Stage 2, 3, or 4 disease; no previous systemic treatment for lymphoma; bi-dimensional measurable disease with at least 1 lesion measuring 〉 2.0 cm in a single dimension; ECOG PS 0-2. Treatment for all patients was given in 28-day cycles for a maximum of 6 cycles. Patients received rituximab 375 mg/m2 IV on days 1, 8, and 15 of cycle 1 (cycles 2-6, rituximab only on day 1); bendamustine 90 mg/m2 IV on days 1 and 2; and bortezomib 1.6 mg/m2 IV on days 1, 8, and 15. Response evaluations were performed after cycle 3 and cycle 6. Patients were permitted to begin maintenance treatment with rituximab 6 months after completion of study treatment and after 6-month follow-up assessments have been conducted. The primary endpoint was to determine the CR rate in this patient population. Secondary endpoints were to assess the ORR, PFS and to characterize the toxicity of this drug combination. Results: Between 3/2010 and 11/2011, 55 patients were enrolled, median age of 64 years (range 30-89), 51% male, 85% stage III or IV. Diagnoses were: FL, 38pts (69%); MZL, 8pts (15%); LPL, 5pts (9%); SLL, 4pts (7%). FLIPI risk for FL pts was low 14 pts (37%), intermediate 18 pts (47%), and high 6 pts (16%). Forty-four pts (80%) completed 6 cycles of BRR, and 67% continued to maintenance rituximab with 35% completing maintenance. The most common grade (G) 3/4 hematologic toxicities were leukopenia (29%), neutropenia (29%) and lymphopenia (16%), and the most common G 3/4 non-hematologic toxicities were neuropathy (9%), diarrhea (7%), and fatigue (7%) (See Table 1). There were no treatment-related deaths and 1 unrelated death on study (embolic stroke). Treatment discontinuation due to toxicity occurred in 11% of pts (2 pts neuropathy, 1 pt each: pancreatitis, atrial fibrillation, erythemia multiforme, and diarrhea). Fifty-one pts were evaluable for response, including 36 FL pts. The overall response rate was 94% (CR 65%, PR 29%) for all pts and 94% (CR 67%, PR 27%) for FL pts. The median FU was 34.8 months (range 9-49). Kaplan-Meier estimates of all pts for progression-free survival (PFS) and overall survival (OS) at 36 mos were 75% and 88% respectively. The 36 mo PFS and OS estimates for FL pts were 73% and 89% respectively. Conclusion: BBR was well tolerated, produced high CR and OR rates and response compares favorably with Phase III of BR. No unforeseen toxicities were noted with this combination. Further study of this regimen in patients with previously untreated low-grade lymphoma is warranted. Table 1. G3/4 Toxicity Hematologic G3 G4 Total Leukopenia 14 (26%) 2 (4%) 16 (29%) Neutropenia 11 (20%) 5 (9%) 16 (29%) Febrile Neutropenia 1 (2%) 0 1 (2%) Lymphopenia 7 (13%) 2 (4%) 9 (16%) Thrombocytopenia 3 (6%) 1 (2%) 4 (7%) Anemia 1 (2%) 1 (2%) 2 (4%) Non-Hematologic Peripheral Neuropathy 5 (9%) 0 5 (9%) Diarrhea 4 (7%) 0 4 (7%) Fatigue 4 (7%) 0 4 (7%) Cough 3 (6%) 0 3 (6%) Rash 2 (4%) 0 2 (4%) Syncope 2 (4%) 0 2 (4%) Disclosures Flinn: Celgene Corporation: Research Funding. Boccia:Incyte Corporation: Honoraria. Berdeja:Array: Research Funding; Curis: Research Funding; Onyx: Research Funding; Abbvie: Research Funding; Acetylon: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Janssen: Research Funding; BMS: Research Funding; MEI: Research Funding; Takeda: Research Funding.

Description: Background Idelalisib (IDELA) is a first-in-class, selective, oral inhibitor of PI3Kδ that reduces proliferation, enhances apoptosis, and inhibits homing and retention of malignant B cells in lymphoid tissues. Phase 1 trials demonstrated that IDELA is highly active as a single agent or in combination with rituximab (R) in heavily pretreated patients (pts) with CLL. Pts in these trials experienced reductions in disease-associated chemokines, improvement of organomegaly and cytopenias, profound reductions in lymphadenopathy, and durable clinical benefit with an acceptable safety profile (Brown 2013; Barrientos 2013). Patients with early progression and significant co-morbidities have limited treatment options; single-agent rituximab is an option in these pts (NCCN 2013; Zelenetz 2013). Methods This Phase 3 study evaluated the efficacy and safety of IDELA + R vs placebo + R in pts with previously treated CLL. Eligibility criteria included the need for treatment per IWCLL guidelines, measurable lymphadenopathy, and CLL progression 6), renal dysfunction, or cytopenias due to poor marrow reserve. All pts received R at 375 mg/m2 [1st dose] and then 500 mg/m2q2 wks x 4, followed by q4 wks x 3 [8 doses total]) and were randomized to Arm A (n=110; IDELA 150 mg BID continuously) or Arm B (n=110; placebo BID continuously). Primary endpoint was progression-free survival (PFS). Response and progression in both arms were assessed by an independent review committee using standard criteria (Hallek 2008; Cheson 2012). Results were reviewed by an external Data Monitoring Committee (DMC). Results Results are from a pre-specified interim analysis after ∼50% of the total number of 119 planned events of CLL progression or death from any cause. Data cutoff was 30 Aug 2013. Pt characteristics (n=220) included a median age of 71 yrs (78% ≥ 65 yrs); CIRS 〉 6 in 85%; median creatinine clearance of 63.6 mL/min; and presence of anemia (73%), thrombocytopenia (61%), neutropenia (34%). Median time since diagnosis was 8.5 yrs, median number of prior therapies was 3 (range: 1-12), 44% had del(17p)/TP53 mutation, and 84% had unmutated IGHV. PFS in the IDELA + R arm was superior to placebo +R (HR [95% CI] = 0.15 [0.08, 0.28]; p = 3.0 x 1011). Median PFS of pts treated with IDELA + R was not reached and for placebo + R was 5.5 mos. At 24 wks, the PFS rate for IDELA +R was 93% compared to 46% for placebo + R. PFS strongly favored IDELA + R in all subgroups, including those with del(17p)/TP53 or unmutated IGHV. Pts treated with IDELA + R and with ≥1 post-baseline assessment also had a superior overall response rate (ORR) relative to those in the control arm (81% vs. 13%; odds ratio 29.9; p = 3.0 x 1019) and a higher lymph node response (LNR) rate (93% vs. 4%; odds ratio 264.5; p = 1.3 x 10-30). Relative to the control group, pts treated with IDELA +R also had a significant improvement in overall survival (OS): HR (95% CI) = 0.28 (0.09, 0.86), p = 0.018. Adverse events (AEs) occurring in ≥20% of pts (any Gr/Gr ≥3) by arm were: pyrexia (IDELA + R 29%/3%; placebo + R 16%/1%), fatigue (IDELA + R 24%/3%; placebo + R 27%/2%), nausea (IDELA + R 24%/0%; placebo + R 22%/0%), chills (IDELA + R 22%/2%; placebo + R 16%/0%), infusion-related reactions (IDELA + R 16%/0%; placebo + R 28%/4%), and cough (IDELA + R 15%/0%; placebo + R 25%/2%). Other selected AEs (any Gr/Gr ≥3) included diarrhea (IDELA + R 19%/4%; placebo + R 14%/0%) and rash (IDELA + R 10%/2%; placebo + R 6%/0%). Select lab abnormalities (any Gr/Gr ≥3) included ALT elevation (IDELA + R 31%/6%; placebo + R 9%/1%), anemia (IDELA + R 26%/6%; placebo + R 30%/14%), neutropenia (IDELA + R 55%/34%; placebo + R 49%/22%), and thrombocytopenia (IDELA + R 17%/10%; placebo + R 26%/16%). The most common SAEs were pneumonia (6.4%), pyrexia (6.4%), and febrile neutropenia (4.5%) in IDELA + R, and pneumonia (8.4%), febrile neutropenia (5.6%), and dyspnea (3.7%) in placebo + R. AEs led to study drug discontinuation in 9 pts (8.2%) in IDELA + R and 11 pts (10.3%) in placebo + R. Based on a review of efficacy and safety, the DMC recommended stopping the study early. Conclusions IDELA + R demonstrated statistically significant improvement with acceptable safety over placebo + R in PFS, ORR, LNR and OS in heavily pretreated pts with relapsed CLL, including those with adverse genetic features. Disclosures: Furman: Gilead Sciences: Research Funding. Sharman:Gilead Sciences: Consultancy, Research Funding. Coutre:Gilead Sciences: Research Funding. Cheson:Gilead Sciences: Research Funding. Pagel:Gilead Sciences: Research Funding. Hillmen:Gilead Sciences: Research Funding. Barrientos:Gilead Sciences: Research Funding. Zelenetz:Gilead Sciences: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Kipps:Gilead Sciences: Research Funding. Flinn:Gilead Sciences: Research Funding. Ghia:Gilead Sciences: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Eradat:Gilead Sciences: Research Funding. Ervin:Gilead Sciences: Research Funding. Lamanna:Gilead Sciences: Research Funding. Hallek:Gilead Sciences: Research Funding. Coiffier:Gilead Sciences: Research Funding. Pettitt:Gilead Sciences: Research Funding. Ma:Gilead Sciences: Research Funding. Stilgenbauer:Gilead Sciences: Honoraria, Research Funding. Aiello:Gilead Sciences: Employment. Johnson:Gilead Sciences: Employment, Equity Ownership. Miller:Gilead Sciences: Employment, Equity Ownership. Li:Gilead Sciences: Employment. Jahn:Gilead Sciences: Employment. Dansey:Gilead Sciences: Employment, Equity Ownership. O'Brien:Gilead Sciences: Research Funding.

Description: Background Pivotal treatment-free remission (TFR) trials require prolonged deep molecular response (MR), often MR4.5, for study entry (Mahon et al. 2010), which has led to increasing focus on MR4.5 as a treatment goal for pts with CML-CP. New tyrosine kinase inhibitors (TKIs), such as nilotinib, more potently inhibit BCR-ABL and elicit significantly deeper and faster MRs than imatinib (Larson et al. 2012), requiring more sensitive techniques to monitor residual disease. In ENESTnext (registered as NCT01227577), MR was evaluated using standard reverse transcriptase quantitative polymerase chain reaction (RQ-PCR) and a microfluidic “digital” PCR assay, which is 〉1-log more sensitive than conventional methods. Methods Pts diagnosed with CML-CP within 6 mo of enrollment were treated with nilotinib 300 mg twice daily (BID) for up to 2 years. RQ-PCR was performed on peripheral blood samples by a central laboratory according to the International Scale (IS). Samples were taken monthly in mo 1-3 and every 3 mo thereafter. The primary endpoint was the rate of confirmed MR4.5 at 2 years, defined as ≥ 2 samples taken 3 mo apart with ≥ 4.5-log reduction of BCR-ABL transcript levels (≤ 0.0032%IS) with a minimum of 25,614 ABL control copies. Pts with suboptimal response or failing treatment (per European LeukemiaNet 2009 recommendations) could dose escalate to nilotinib 400 mg BID per physician discretion. Complete cytogenetic response (CCyR) and major MR (MMR, 3-log reduction of BCR-ABL transcript levels [≤ 0.1%IS]) were also assessed. In an exploratory analysis, samples identified as MR4.5 using conventional RQ-PCR were also evaluated using the Fluidigm digital PCR platform (Oehler et al. 2009). BCR-ABL copy number was estimated by Poisson distribution; samples were positive if copy number was 〉 0. The data cutoff date for this analysis was April 30, 2013. Results Of 128 pts, 64 (50%) were male and 103 (80%) were white. The mean age was 55.6 y (range, 21.0-89.0). Pts were treated for a median of 8.5 mo (range 0.1-24.1); median daily nilotinib dose was 600 mg. As of the data cut, 87, 36, 23 and 18 pts have been treated for ≥ 6, ≥ 12, ≥ 18 and ≥ 22 mo, respectively. Cumulative incidence of MR4.5, MMR and CCyR was 22 (17%), 76 (59%) and 72 (56%) pts, respectively. In the 22 pts who achieved MR4.5, the mean time to first MR4.5 was 6.4 mo (range, 1.0-22.7). Digital PCR was performed on 57 samples from these 22 pts; 15/22 pts had ≥ 2 samples from different time points. Of these, 8 were initially positive for BCR-ABL and became negative, 5 were initially negative and remained negative and 2 were initially positive and remained positive. Achieving BCR-ABL negativity using digital PCR generally occurred rapidly (within 3 mo of MR4.5). The most common (≥ 2 pts) grade 3 adverse events (AEs) were nausea (n = 4), headache (n = 3), elevated lipase level (n = 12), thrombocytopenia (n = 6), neutropenia (n = 6), hypophosphatemia (n = 5), anemia (n = 4) and increased amylase level (n = 3). Grade 4 AEs were myocardial infarction (n = 2), device-related infection (n = 1), elevated lipase level (n = 4), thrombocytopenia (n = 3), neutropenia (n = 2) and hyponatremia (n = 1). To date, 22 (17%) pts have discontinued treatment. Reasons included AEs (n = 11), withdrawn consent (n = 3), protocol deviation (n = 2), unsatisfactory therapeutic effect (n = 2), abnormal laboratory values (n = 2), abnormal test procedure result (n = 1) and loss to follow-up (n = 1). Conclusions Treatment with nilotinib 300 mg BID in pts with newly diagnosed CML-CP resulted in rapid and substantial rates of MR4.5 using conventional RQ-PCR, with a safety profile similar to that reported in previous studies. The digital PCR assay detected residual BCR-ABL in approximately 50% of samples with at least MR4.5 by RQ-PCR, and showed declining BCR-ABL levels with continued therapy. Thus, use of digital PCR may help better identify appropriate candidates for TFR studies. Based on results from the ENESTnd trial (Larson et al. 2012), MR4.5 rates are expected to increase over time. Other studies have demonstrated that pts who achieve early, deep MR have improved long-term outcomes (Marin et al. 2012). Evaluation of longer-term outcomes for patients with negative digital PCR results is ongoing. Disclosures: Mauro: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau. Off Label Use: This abstract describes a clinical trial evaluating the investigational agent midostaurin for use in patients with advanced systemic mastocytosis. Radich:novartis: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Ariad: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Incyte: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Cortes:Pfizer: Consultancy, Research Funding; Novartis: Research Funding; Bristol Myers Squibb: Research Funding; Ariad: Consultancy, Research Funding; Teva: Consultancy, Research Funding. Keir:Novartis: Employment, Equity Ownership. Yi:Novartis: Employment. Goldberg:Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding, Speakers Bureau; Ariad: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Description: 43 patients with acute myeloid leukemia have undergone transplantation at our institution over the past 14 years. Patient selection criteria included age less than 70 years, creatinine less than 2mg/ml, no active infection, cardiac ejection fraction 〉40%, DLCO 〉 50% of predicted and no other co-morbid conditions that would jeopardize survival. 39 patients were in first remission, 4 were in second or higher remission. 3 patients had favorable cytogenetics, 40 had intermediate or unfavorable cytogenetics. After achieving remission for at least 30 days, patients were consolidated with Etoposide and AraC, followed by G-CSF. Hematopoietic stem cells were collected when the WBC rebounded to at least 10,000/μl. The target dose of CD34 positive cells was 5×106/kg. The minimum dose given was 2.3 × 106/kg). High dose therapy consisted of Busulfan 1mg/kg and Etoposide 60mg/kg. The average age at transplantation was 42 years (range 20 to 61). Days of neutropenia (AGC

Description: 35 patients with acute myeloid leukemia have undergone transplantation at our institution over the past 12 years. Patient selection criteria included age less than 70 years, creatinine less than 2mg/ml, no active infection, cardiac ejection fraction 〉40%, DLCO 〉 50% of predicted and no other co-morbid conditions that would jeopardize survival. 31 patients were in first remission, 4 were in second or higher remission. 3 patients had favorable cytogenetics, 25 had intermediate or unfavorable cytogenetics. After achieving remission for at least 30 days, patients were consolidated with Etoposide and AraC, followed by G-CSF. Hematopoietic stem cells were collected when the WBC rebounded to at least 10,000/ml. The target dose of CD34 positive cells was 5x106/kg. The minimum dose given was 2.3 x 106/kg). The average age at transplantation was 41 years (range 22 to 61). Days of neutropenia (AGC

Description: ATN-224 (bis-choline tetrathiomolybdate) is an orally-available small molecule that is currently being studied in several phase II oncology clinical trials. ATN-224 inhibits copper-zinc superoxide dismutase (Cu/Zn-SOD; SOD1) in endothelial and tumor cells. SOD1 is an enzyme that mediates signaling by a number of mitogens including VEGF, FGF-2, EGF, IGF-1 and PDGF. The inhibition of SOD1 by ATN-224 leads to the inhibition of proliferation in endothelial cells and the induction of apoptosis in tumor cells. In a preclinical mouse model using multiple myeloma (MM) cells obtained from a patient that was refractory to bortezomib, the combination of ATN-224 and bortezomib was more effective than either agent alone and led to tumor regression. Based on this data, a phase I/II clinical study evaluating the combination of ATN-224 and bortezomib for MM patients that had previously failed bortezomib was initiated. The phase I portion of this study evaluated the safety of several doses of both ATN-224 and bortezomib and established a recommended dose and schedule of this combination for the phase II portion of the study. The phase I study has completed enrollment and results are presented here. Patients with recurrent or refractory MM that had previously failed bortezomib and currently showing evidence of disease progression were enrolled. Patients had adequate ECOG performance status (PS 0–2) and hematologic and organ function. Patients were monitored for safety and preliminary evidence of efficacy. Blood samples were collected at specific intervals for pharmacokinetic and pharmacodynamic analyses. Twenty-one patients (62% male), aged 46–80 (mean 66) with PS 0–1 were enrolled into 6 cohorts. Dose Limiting Toxicity (DLT) was defined as grade 3 or 4 neutropenia with neutropenic fever, grade 4 neutropenia, grade 3 or 4 thrombocytopenia, grade 2 peripheral neuropathy with pain, grade 3 or 4 neuropathic pain and/or peripheral sensory neuropathy, grade 4 anemia or a fall in hemoglobin by 〉3 g/dL when day 1 hemoglobin is ≥11 g/dL or 〉2 g/dL when day 1 hemoglobin is 2g/dL from baseline (n=3) and grade 3 fatigue (n=1)] were observed within the first three cohorts. After review of this data, it was determined that the more appropriate dosing schedule included a 7 day drug holiday. In cohorts 4 through 6 (n=11), ATN-224 was administered at doses of either 180 or 210 mg daily for 21 days in combination with bortezomib at a dose of either 1.0 or 1.3 mg/m2/dose on days 8,11, 15 and 18 of a 28 day cycle. One DLT (grade 4 thrombocytopenia) was observed and occurred in the 180 mg ATN-224 plus 1.3mg/m2/dose bortezomib cohort. By incrementally increasing each dose of ATN-224 and bortezomib individually and modifying the treatment schedule, treatment-related toxicities have been minimized while maximizing the treatment doses. One patient experienced a complete response that was durable for over 10 months. The other 20 patients experienced disease progression within 90 days. A daily dose of 210 mg of ATN-224 for 21 days and a dose of bortezomib at 1.0 mg/m2 on days 8, 11, 15, and 18 of a 28 day cycle was well tolerated and recommended for the phase II portion of this trial, which is now enrolling patients. The phase I portion of the study demonstrates that the combination of ATN-224 and bortezomib can be safely administered and may be an effective treatment for MM patients that are relapsed from or refractory to bortezomib.

Description: Background SGI-110 is second generation HMA formulated as a dinucleotide of decitabine (DAC) and deoxyguanosine delivered as a small volume, pharmaceutically stable SQ injection allowing longer half-life and more extended decitabine exposure than DAC IV infusion. SGI-110 differentiated pharmacokinetic profile resulted in potent hypomethylation and clinical responses in previously treated MDS and AML patients in the phase 1 trial (Kantarjian et al. 2012). Methods In a randomized Phase 2 study, relapsed/refractory AML, or elderly treatment naïve AML patients who were not suitable for induction chemotherapy (poor major organ function; poor cytogenetics; or secondary AML) were randomized to one of two SQ doses – the biologically effective dose (BED) of 60 mg/m2 QDx5 or 90 mg/m2 QDx5. The primary endpoint of the phase 2 study is the overall remission rate (CR, CRi, and CRp) based on the International Working Group Criteria 2003. Safety findings based on adverse events (AEs) as graded by the CTCAE v4 criteria and pharmacodynamic data on Long Interspersed Nucleotide Element (LINE-1) DNA methylation (an index of global DNA methylation) activity were also assessed and reported. Results As of June 30, 2013, sixty-seven patients (50 relapsed/refractory AML, 17 treatment naïve elderly AML) were treated and had a minimum follow up of 3 months. Patients were randomized to either 60 mg/m2 dose (32 patients) or 90 mg/m2 dose (35 patients). The median age was 66 years (range, 22–84), 69% were male, and ECOG PS of 0/1/2 was reported in 11/47/9 patients respectively. Median number of prior regimens was 2 (range, 0–10). Patients’ characteristics were well balanced between the 2 dose groups. The primary endpoint of overall remissions (CR, CRp, or CRi) was observed in 17/67 patients (25% with 95% CI, 16–37%). There were 8 complete remissions (CR, CRp, or CRi) in 50 patients with relapsed/refractory AML (16% with 95% CI, 7-29%); and 9 complete remissions (CR, CRp, or CRi) in 17 treatment-naïve elderly AML patients (53% with 95% CI, 28-77%). Five patients (4 relapsed/refractory, and one treatment-naïve elderly AML) subsequently received a stem cell transplant. There was no difference in the complete remission rate between 60 and 90 mg/m2 doses (8 remissions in 32 patients at 60 mg/m2, and 9 remissions in 35 patients at 90 mg/m2). LINE-1 DNA methylation data before and after treatment was available in 50 (75%) patients enrolled. LINE-1 demethylation ≥ 10% post treatment was observed in 83% and 78% in the 60 mg/m2 and 90 mg/m2, respectively. The median maximum LINE-1 demethylation for responders is 25% as compared to 19% for non-responders. The most common adverse events (AEs) regardless of relationship to SGI-110 ≥ Grade 3 include febrile neutropenia, thrombocytopenia, anemia, leukopenia, neutropenia, and pneumonia. The 90 mg/m2 dose showed a greater frequency of Grade 3/4 related AEs ≥ 10% (anemia, febrile neutropenia, leukopenia, neutropenia, and thrombocytopenia) compared to the 60 mg/m2 dose. Conclusions SQ SGI-110 is a new HMA which is well tolerated and clinically active in the treatment of AML. Complete remissions and potent demethylation of ≥10% were equally observed at the 2 dose groups of 60 and 90 mg/m2. These data support further phase 3 investigation of this agent in the treatment of AML. Preliminary overall remission rate of 53% in treatment-naïve elderly AML seems to compare favorably with previous results reported for HMA treatment but this needs to be confirmed in a larger number of patients and randomized studies. Disclosures: Kantarjian: Astex Pharmaceuticals, Inc.: Research Funding. Jabbour:Astex Pharmaceuticals, Inc.: Research Funding. Yee:Astex Pharmaceuticals, Inc.: Research Funding. Kropf:Astex Pharmaceuticals, Inc.: Research Funding. O'Connell:Astex Pharmaceuticals, Inc.: Research Funding. Stock:Astex Pharmaceuticals, Inc.: Research Funding. Tibes:Astex Pharmaceuticals, Inc.: Research Funding. Rizzieri:Astex Pharmaceuticals, Inc.: Research Funding. Walsh:Astex Pharmaceuticals, Inc.: Research Funding. Griffiths:Astex Pharmaceuticals, Inc.: Research Funding. Roboz:Astex Pharmaceuticals, Inc.: Honoraria, Research Funding. Savona:Astex Pharmaceuticals, Inc.: Research Funding. Ervin:Astex Pharmaceuticals, Inc.: Research Funding. Podoltsev:Astex Pharmaceuticals, Inc.: Research Funding. Pemmaraju:Astex Pharmaceuticals, Inc.: Research Funding. Daver:Astex Pharmaceuticals, Inc.: Research Funding. Garcia-Manero:Astex Pharmaceuticals, Inc.: Research Funding. Borthakur:Astex Pharmaceuticals, Inc.: Research Funding. Wierda:Astex Pharmaceuticals, Inc.: Research Funding. Ravandi:Astex Pharmaceuticals, Inc.: Research Funding. Cortes:Astex Pharmaceuticals, Inc.: Research Funding. Brandwein:Astex Pharmaceuticals, Inc.: Research Funding. Odenike:Astex Pharmaceuticals, Inc.: Research Funding. Feldman:Astex Pharmaceuticals, Inc.: Research Funding. Chung:Astex Pharmaceuticals Inc.: Research Funding. Naim:Astex Pharmaceuticals, Inc.: Employment. Choy:Astex Pharmaceuticals, Inc.: Employment. Taverna:Astex Pharmaceuticals, Inc.: Employment. Hao:Astex Pharmaceuticals Inc.: Employment. Dimitrov:Astex Pharmaceuticals, Inc.: Employment. Azab:Astex Pharmaceuticals, Inc.: Employment. Issa:Astex Pharmaceuticals, Inc.: Consultancy, Research Funding.