7075 Background: L is active in myelodysplastic syndromes and myeloma and may also have activity in AL or CLL. Methods: A phase I dose escalation study of L in separate cohorts of relapsed AL or relapsed CLL, respectively, is ongoing. L was given initially at 25mg/day orally on days 1–21 of repeated 28 day cycles in both cohorts. Results: In AL, 12 patients (pts) have enrolled to date (11-AML) with a median age of 62 years (range, 22–79). 4 pts were treated at dose level 1 (25mg/day) and 8 at level 2 (35mg/day). One DLT was seen at level 2: an AML pt, age 79, died suddenly of uncertain cause (no pulmonary embolism), and the level was expanded. 3 pts had early progression and were replaced (pts were not evaluable for toxicity). Complete remission (CR) occurred in two pts. At level 1, a 74 year old with AML and normal karyotype in 2nd relapse, with widespread leukemia cutis but no blood/marrow involvement, had remarkable resolution of disease after 2 cycles and is in CR after 4 cycles. At level 2, a 69 year old with AML and trisomy 13 had CR (by IWG criteria, including cytogenetic CR) after 2 months. In the CLL cohort, 4 pts (ages 43–60 with 2–9 prior therapies) have enrolled. 3 pts were given the initial starting dose of 25mg/day. Each had early or late DLT including serious tumor flare in 2 cases, one with airway obstruction due to massive tonsillar adenopathy requiring emergent tonsillectomy. The tonsil had increased expression of Ki67, CD3, CD4, CD8, and granzyme B positive cells after L, relative to a pretreatment node. Due to excess toxicity with the 25mg initial dose, a 2.5mg/day dosing schedule with gradual intra-patient escalation was initiated. 1 pt has enrolled at this dose to date. Pharmacodynamic (PD) studies in CLL demonstrate L-induced B-cell activation (upregulation of CD40 and CD86) that may correlate with development of tumor flare. Conclusions: L induced CR in 2 cases of relapsed non-del 5q AML. Dose escalation continues in AL. In CLL, higher doses had unacceptable toxicity; low dose followed by gradual intra-patient dose escalation is being pursued. PD studies suggest B-cell activation may contribute to development of tumor flare in CLL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene