ALBERT

Description: Abstract 2800 Background: Pralatrexate (FOLOTYN®) is an antifolate designed for preferential tumor uptake and accumulation. Pralatrexate was granted accelerated approval by the US Food and Drug Administration at a dose of 30 mg/m2 weekly for 6/7 weeks for relapsed or refractory peripheral T-cell lymphoma. Given that cutaneous T-cell lymphoma (CTCL) is often an indolent disease treated in a maintenance fashion, the goal of this trial was to identify a dose with clinical activity and minimal toxicity to allow continuous or maintenance treatment. In the present study, designated PDX-010, the initial dose of pralatrexate for relapsed or refractory CTCL was based on data showing that 30 mg/m2 demonstrated activity in patients with aggressive lymphoma. A dose de-escalation strategy was used in PDX-010 to identify an optimal dose for CTCL. Methods: Eligibility included CTCL histology of mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large-cell lymphoma, with disease progression after at least 1 prior systemic therapy, and written informed consent. The starting dose and schedule was 30 mg/m2 of pralatrexate by intravenous (IV) push weekly for 3/4 weeks. If toxicity as defined per the protocol was observed, subsequent cohorts received reduced doses (20, 15, 10 mg/m2) and/or schedules (weekly for 3/4 or 2/3 weeks). All patients received supplementation with vitamin B12 1 mg intramuscularly every 8 to10 weeks, and folic acid 1 mg orally once daily (QD). Response was evaluated by the modified severity weighted adjustment tool (mSWAT) every 2 cycles for 6 months, and then every 4 cycles. For patients with lymph node involvement, scans were completed at baseline and upon clinical response or end of treatment, whichever occurred first. Results: Fifty-four patients were treated across 2 stages of this study. In the dose-finding phase, 31 patients were sequentially enrolled into 6 cohorts and treated at varying doses and schedules. The optimal dose and schedule, as defined in the protocol, was identified as 15 mg/m2 weekly for 3/4 weeks, based on the tolerability and efficacy (overall response rate [ORR] of 50%) observed in the initial 6 patients in that cohort. Among the 31 patients in the dose-finding stage, the ORR for patients treated at a dose intensity ≥15 mg/m2 weekly for 3/4 weeks was 61% (11/18), and the ORR for those patients treated in lower-dose cohorts was 8% (1/13). The second stage of the study included 23 additional patients treated at 15 mg/m2 weekly for 3/4 weeks, for a total of n = 29 patients treated at this optimal dose. Among these 29 patients, the median number of prior systemic therapies was 4.5 (range 1 to 11), and patients received pralatrexate for a median of 4 cycles (range 1 to 23). Patients enrolled in this cohort could be dose-escalated at investigator discretion if there was an absence of toxicity and a response 〈 CR. At this time 53/54 patients treated in this study are evaluable for efficacy, including 28/29 patients treated at 15 mg/m2 for 3/4 weeks. At the optimal dose, the ORR was 43% (12/28) and 50% (20/40) in patients treated at a dose intensity ≥15 mg/m2 weekly for 3/4 weeks. At the optimal dose/schedule, grade 1–2 adverse events (AEs) occurring in 〉10% were fatigue (34%), mucositis (28%), nausea (24%), edema (24%), epistaxis (21%), pyrexia (17%), constipation (14%), and vomiting (14%). The only grade 3 AE in 〉10% was mucositis (17%). Hematologic toxicities were limited to grade 3 neutropenia (3%), grade 1–2 anemia (14%), grade 3 anemia (3%), grade 1–2 thrombocytopenia (7%), grade 3 thrombocytopenia (3%), grade 1–2 leukopenia (3%), and grade 4 leukopenia (3%). No grade 4 nonhematological toxicities were observed. Conclusions: Pralatrexate shows high activity with acceptable toxicity in patients with relapsed or refractory CTCL at the identified optimal dose and schedule of 15 mg/m2 weekly for 3/4 weeks. The lack of significant hematologic toxicity or cumulative toxicity seen in this study suggests that pralatrexate should be further evaluated as continuous or maintenance therapy for patients with CTCL. Final efficacy and tolerability data will be reported. Disclosures: Horwitz: Allos Therapeutics, Inc.: Consultancy, Research Funding. Foss:Allos Therapeutics, Inc.: Consultancy, Speaker. Zain:Allos Therapeutics, Inc. : Speakers Bureau. Lechowicz:Allos Therapeutics, Inc.: Consultancy; Celgene Corporation : Consultancy. Shustov:Allos Therapeutics, Inc.: Honoraria, Research Funding. Koutsoukos:Allos Therapeutics, Inc.: Employment. Fruchtman:Allos Therapeutics, Inc.: Employment. O'Connor:Allos Therapeutics, Inc.: Research Funding. Duvic:Allos Therapeutics, Inc.: Research Funding.

Description: Background: Subcutaneous Panniculitis-like T-cell lymphoma (SPTCL) is a rare, often aggressive T-cell lymphoma. Recently it has been appreciated that there are two clinical courses, whereby some patients have rapidly progressive disease and others have a chronic course. The likelihood of an aggressive course may be dependent on the T-cell receptor phenotype expressed by the tumor, with γ/δ expression portending a worse outcome than α/β expression. In the WHO-EORTC classification γ/δ expressing cases of SPTCL are provisionally renamed as Primary Cutaneous γ/δ T-cell lymphoma. Although most reported cases have been treated with combination chemotherapy, there are no prospective trials for the treatment of SPTCL. With chemotherapy, only a minority of patients have durable remissions; the majority have either primarily refractory disease or relapses. Bexarotene is an oral retinoid used for the treatment of mycosis fungoides and other T cell lymphomas. Patients and methods: We treated eight SPTCL patients with bexarotene. There were four women and four men, with a median age of 56 years (range 23–80). All patients presented with disseminated subcutaneous nodules, Stage IV, but without extracutaneous involvement. Three patients presented with pancytopenia, without bone marrow involvement, suggestive of hemophagocytic syndrome. Four patients had an elevated LDH and four had ECOG PS 〉 2. Five patients received bexarotene as primary treatment. Three patients had progression of disease after previous combination chemotherapy. Doses of bexarotene ranged from 100mg/m2 – 450 mg/m2. All patients received at least one month of therapy. Results: Overall 5/8 (63%) patients responded. Two patients progressed at one and three months. One of these patients could only tolerate 100mg/m2. One patient had stable disease for four months. Two patients had partial responses (PR) lasting 10 and 18 months. One of the PR patients was given chemotherapy to induce a remission prior to a planned allogeneic stem cell transplant. They progressed on CHOP and ICE and then responded again to bexarotene. Three patients achieved a complete response (CR). Two remain in CR at 14 and 26 months on bexarotene. The other patient had a CR lasting 33 months. Bexarotene was then discontinued due to hypertriglyceridemia, and the patient developed new lesions within three months. As expected with bexarotene, toxicities of treatment were limited to hypertriglycerides and hypothyroidism. IPI was not predictive of response to therapy. Both patients with documented γ/δ T-cell receptors achieved a PR. Conclusion: Bexarotene showed a high response rate in SPTCL, which characteristically responds poorly to chemotherapy. These responses included patients with both γ/δ and α/β T-cell receptors. Given bexarotene’s favorable toxicity profile and demonstrated activity, it represents an excellent treatment option for patients with this rare T-cell lymphoma. Further study is required to determine whether bexarotene is best used as a single agent, or as part of combination or sequential therapies.

Description: Abstract 2643 Background: Granulomatous mycosis fungoides (GMF) is a variant of MF/cutaneous T-cell lymphoma characterized by a prominent granulomatous infiltrate in addition to the malignant lymphoid infiltrate. The diagnosis of GMF remains challenging due to variable clinical and histopathologic features. The significance of granuloma formation in CTCL is unclear and whether patients with GMF have a distinct prognosis compared to patients with classic type of MF is controversial. Data are scarce and long term results are not available. Objectives: To evaluate the clinical, histopathologic, prognostic significance and therapeutic responses of patients with GMF and to compare results to age and stage-matched patients with classic type of MF. Methods: A single center retrospective case-case study was performed at Memorial Sloan-Kettering Cancer Center of 430 patients with a diagnosis of MF between January 1981 and April 2012. Available histopathology slides were reviewed for the presence of granulomas or histiocytes comprising ≥ 25% of the atypical lymphoid infiltrate. Each identified case was matched with two classic MF cases via age and TNMB stage. For each case meeting criteria, the medical records, photographs, and histopathology slides were reviewed. Results: Twenty-seven patients with GMF were identified representing 6.3% of all MF patients at our center. Patient demographics were similar between the GMF group and case-control classic MF group, with a male-to-female ratio of 2.1:1 and a median age of 57. Most GMF patients (69%) present at early stages (IA-IIA). Patients with GMF had a longer onset of disease prior to diagnosis (median, 4.5 years vs 3.0 years). Skin manifestations of granulomatous MF showed a great variability, but were not distinguishable from those of classic MF. Histological findings showed an atypical predominantly CD4+ lymphocytic infiltrate with either granuloma formation or histiocytes with giant cells. TCR rearrangement was positive in 70% of cases. Features of GMF were present at initial diagnosis in 17 patients. In 10 patients, granulomatous infiltrates appeared at an average of 5.4 years after MF diagnosis. Secondary malignancies developed in 38% of patients with GMF compared to 23% of patients in the case-control classic MF group. Among the GMF patients, there was a trend towards fewer CRs to any treatment (38% vs 54%; p = 0.21); fewer PRs or CRs with topical therapy (57% vs 83%; p = 0.002) and with UV-light therapy (62% vs 90%; p = 0.008). Significantly more GMF patients received systemic therapy (66.7%) compared to classic MF patients (32.7%; p = 0.006). They also required a longer time to achieve best response (median 35 months vs 9 months, p = 0.002) compared to the control group. Disease progression to higher stage was seen in 46% of cases in the GMF group compared to 30% of cases in the classic MF group (p = 0.23). The 5-year and 10-year progression-free survival rates were significantly lower in the GMF group (59% and 33%, respectively) compared to the control group (84% and 56%, respectively; p = 0.02). However, the 5-year and 10-year overall survival rates were similar between GMF (86% and 72%, respectively) and classic MF patients (85% and 85%; p = 0.54). Conclusion: Our study presents the largest series on GMF in the United States. Most patients with GMF show similar clinical features when compared to patients with conventional MF. The clinical features do not reflect the histologic findings of granulomas. More frequent disease progression and poorer response to skin-directed therapies are seen in GMF patients compared to classic MF; however, overall survival is not significantly different. The majority of GMF patients present with granulomatous features at initial diagnosis and in subsequent biopsies suggesting that this entity has a unique relationship with its microenvironment. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2706 Objective: Adult T-cell leukemia/lymphoma (ATLL) is a mature T-cell malignancy associated with human T-cell lymphotropic virus -1 (HTLV-1) infection. Four clinical subtypes are recognized including acute/lymphomatous (aggressive) or chronic/smouldering (indolent). For the aggressive subtypes the median overall survival is 6 months despite aggressive combination chemotherapy. Novel therapeutic targets against CD25, CD52, and NF μB have shown preliminary activity in ATLL. Recently, the chemokine receptor 4 (CCR4) antibody (KW-0761) was approved in Japan based on a phase II overall response rate of 50% and median overall survival of 13.7 months in 28 patients with relapsed/refractory ATLL. CD30 (Ki-1) is a marker of immune activation expressed on lymphocytes, and is an emerging target in lymphoma. The novel antibody-drug conjugate brentuximab vedotin targets CD30 and has shown efficacy in Hodgkin lymphoma and anaplastic large cell lymphoma (ALCL). While CD30 positive ATLL is infrequent in Japanese ATLL patients, ranging from 12.1% to 19.4%, the prevalence of CD30 positive ATLL outside of Japan has not been extensively studied. Patients and Methods: To investigate the prevalence of CD30 expression and its importance in ATLL outside of Japan we conducted a retrospective review of all patients who underwent treatment or consultation for ATLL at our institution between 1998 and 2012. Individual chart review was performed to report the clinical presentation, pathological features, and outcomes. Pathology review of CD30 expression status was conducted if specimens were available. The CD30 (Ber-H2) antibody from Ventana was used on automated platforms per manufacturer's instructions. Specimens were determined to be positive if the CD30 expression was 〉20% by an expert hematopathologist (AC). Results: We identified 50 patients with ATLL. Patient characteristics were: median age 54 (range 30–82); male:female 19:31; Caribbean-39, American-6, Western African-2, Peruvian-2, and Greek-1. Subtype of disease at diagnosis was: Acute/Lymphomatous—41 and Chronic/Smouldering—9. Thirty-six of 50 (72%) patients' samples had been tested at least once for CD30. Eighteen patients (50%) were reported positive. Of all cases reviewed (N=50), eight had pathology available for confirmatory review. Of those, five patients remained positive, 1 patient was reclassified as positive after initially being reported as negative, and two remained negative. The median overall survival of all patients was 13 months. In the subset who had CD30 status assessed the median overall survival for CD30 negative and positive ATLL was 18 and 45 months respectively (p=0.116). Conclusions: CD30 expression on normal lymphocytes is rare. Our retrospective data suggests that ATLL patients presenting outside of Japan may demonstrate CD30 positivity at a higher prevalence compared to Japanese reports. In pre-clinical studies of CD30 positive ATLL, SGN-35 has been shown in vitro and in vivo to demonstrate similar cytotoxicity compared to ALCL (Maeda et al. Cancer Sci 2010). Novel strategies are clearly needed to improve the outcome of ATLL despite recent advances. Therefore, CD30 testing may be considered in ATLL as a novel target for future research strategies. Disclosures: Matasar: GSK: Research Funding; Genentech: Consultancy. Straus:Seattle Genetics: Consultancy. Zelenetz:GSK: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Gilead: Consultancy; Sanofi Aventis: Consultancy; Cephalon: Consultancy; Celgene: Consultancy; Seattle Genetics: Consultancy; Amgen: Research Funding. Horwitz:Seattle Genetics: Consultancy, Research Funding; Allos: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy; Genzyme: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy; Johnson & Johnson: Consultancy; Infinity Pharmaceuticals, Inc.: Research Funding.

Description: Bexarotene, a synthetic retinoid ligand for the retinoid X receptor (RXR), is a highly active agent in the treatment of relapsed or refractory CTCL with a response rate of ~45% (Arch Dermatol137: 581–93, 2001; J Clin Oncol19: 2456–71, 2001). Interferon alfa has a similar response rate although the doses and responses in the literature have varied. Promising results have been reported with combinations of retinoids and interferon alfa, including bexarotene (J Am Acad Dermatol50: 375–9, 2004). To explore this combination, a phase II trial was designed in which patients with CTCL were treated with bexarotene 300 mg/m2/day for at least 8 weeks. If less than a complete response was seen at this time, interferon alfa-2b at a dose of 3 million units escalated to 5 million units subcutaneously 3 times weekly was added for another 8 weeks. Responding patients could continue treatment beyond 16 weeks. Twenty-two patients with CTCL were enrolled in the trial: median age 58 years (22–79); 9 males, 13 females, TNM stages: IB (3), II (7), III (4), IV (8). One patient had no prior treatment; the rest had relapsed or refractory disease with a mean of 49 months from initial diagnosis to enrollment. Four patients had previously received bexarotene and 2 interferon alfa. Seventeen patients completed 16 weeks of treatment and are assessable for response, 1 has not completed 16 weeks and 4 received less than 16 weeks (1 early death, 1 non-compliant, 1 withdrawal of consent because of side effects, and 1 myocarditis, probably not treatment-related). Using reproducible objective criteria for response utilized in the single agent bexarotene trials cited above (Primary Endpoint Classification), 6 of 17 patients achieved a partial response and 1 a complete response (objective response rate 41%, 95% confidence intervals 18%–67%). Three of the 6 partial responses occurred with bexarotene alone at 8 weeks. Median duration of response was 2.7 months, range 1.1–7.6 months. Reversible grade 3 or 4 toxicities seen in more than 1 patient were hypercholesterolemia (2 pts.), hypertriglyceridemia (4 pts.), neutropenia (3 pts.), lymphopenia (2 pts.) and elevated AST in 2 patients. Lipid lowering agents were used in all patients. Six patients died, all of progressive disease from 1.6–29.9 months following initiation of treatment. The major response rate for the combination of bexarotene and interferon alfa is similar to that for bexarotene alone. Despite the wide confidence intervals that indicate that a small advantage might be missed by not increasing accrual, the clinical usefulness of this combination is limited by the inconvenience of interferon injections. Further trials in CTCL are planned combining bexarotene with other agents, including active cytotoxics.

Description: Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1. A dose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after ≥ 1 prior systemic therapy. The starting dose and schedule was 30 mg/m2/wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m2/wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fifty-four patients were treated. The recommended regimen was identified as 15 mg/m2/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m2/wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.

Description: Cutaneous T-cell Lymphoma (CTCL) is a heterogeneous group of diseases, derived from skin resident or skin homing T-cells, with Mycosis Fungoides (MF) and Sezary Syndrome (SS) being the most common subtypes. Although CTCL is the best-studied group among T-cell malignancies, our understanding of its pathogenesis remains limited, due to the paucity of comprehensive, large-scale genomic studies. Recent whole exome and targeted sequencing approaches have primarily elucidated mutations in genes affecting immune synapse signaling (PLCG1, CD28, JAK3) and epigenetic modulation (ARID1A, DNMT3A) in both MF and SS. In search of novel genetic alterations, we applied deep targeted sequencing in 71 freshly cryopreserved skin or peripheral blood samples derived from 61 patients with CTCL, including patients with MF, SS, primary cutaneous anaplastic large cell lymphoma (pcALCL), pleomorphic small/medium sized CD4+ CTCL and CD8+ CTCL. Genomic DNA was sequenced for the entire coding region of 585 known cancer-related genes on a HiSeq2500 Illumina instrument with a mean depth of 1000X. Sequences were analyzed for base substitutions, in-frame or frameshift insertions and deletions and splicing variants. Known germline variants reported at dbSNP and the 1,000 Genomes Project data were excluded, while confirmed somatic variants previously reported at the COSMIC database were included. Only variants with an allele frequency above 2% were further analyzed, in order to eliminate false positive data. Recurrent mutations were identified in genes responsible for tumor suppression (TP53, FAT1, FAT3), DNA damage response (ATM, MDC1), DNA mismatch repair (MSH3), chromatin remodeling (ARID1B), histone methylation (MLL2, MLL3, KDM6A) and DNA methylation (DNMT1). Moreover recurrent mutations pointed to robust activation of the three following signaling pathways: Receptor Tyrosine Kinase (IRS2, FOXO3) JAK/STAT (JAK3, STAT5A/B, SOCS1) and NOTCH (NOTCH1, NOTCH2). Finally, at a subclonal level we paradoxically identified mutations of the Androgen Receptor (AR) gene. Interestingly, the presence of large cell features correlated with a higher accumulation of molecular events, since transformed MF and pcALCL had a significantly higher number of genetic alterations compared to untransformed MF (Figure 1). In sum, the genomic landscape occurring from our targeted sequencing approach highlights the pathologic complexity of these neoplasms, suggesting multiple non-redundant mechanisms leading to lymphomagenesis. The characterization of this cohort is expected to provide an opportunity to comprehend intra-CTCL molecular heterogeneity and offer a better classification of CTCL entities along with novel potential therapeutic targets. Figure 1. Figure 1. Disclosures Levine: Foundation Medicine: Consultancy; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees; Loxo Oncology: Membership on an entity's Board of Directors or advisory committees. van den Brink:Merck: Honoraria; Boehringer Ingelheim: Consultancy, Other: Advisory board attendee; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria; Tobira Therapeutics: Other: Advisory board attendee. Palomba:Janssen: Consultancy.

Description: Abstract 919 Background: Pralatrexate enters cancer cells via the reduced folate carrier-1 (RFC-1) and is efficiently polyglutamated by folylpolyglutamyl synthetase (FPGS), leading to high intracellular retention. In a Phase 1/2 study of patients with hematologic malignancies, pralatrexate demonstrated activity in aggressive T-cell lymphoma with a maximum tolerated dose (MTD) of 30 mg/m2 once weekly for 6 of 7 weeks. The generally indolent course of CTCL may be better treated at lower doses in a maintenance fashion if a lower incidence and severity of adverse events can be achieved while preserving activity. PDX-010 is an open-label, single-agent, multicenter, Phase 1 dose-reduction trial in patients with relapsed or refractory CTCL. The primary objective is to identify an optimal dose and schedule of pralatrexate for these patients. Methods: Eligibility included mycosis fungoides (MF), Sézary syndrome (SS), and primary cutaneous anaplastic large cell lymphoma (ALCL); with disease progression after at least 1 prior systemic therapy. The pralatrexate dose and schedule started at 30 mg/m2 by IV push on 3 of 4 weeks and subsequent cohorts received reduced doses (20, 15, 10 mg/m2) and/or schedules (3/4 or 2/3 weeks) of pralatrexate based on tolerability. All patients received supplementation with vitamin B12 1 mg intramuscularly every 8-10 weeks and folic acid 1 mg orally once daily. As we sought a well tolerated regimen the definition of DLTs to trigger dose reduction included toxicities such as grade ≥ 3 neutropenia, grade ≥ 2 thrombocytopenia, febrile neutropenia, grade ≥ 2 mucositis/stomatitis, and any toxicity leading to dose omission or reduction in cycle 1. If DLT occurred and a response was seen, the following cohort was opened at the next lower dose or next less frequent schedule. Response was evaluated by modified severity-weighted adjustment tool (SWAT) every 2 cycles for 6 months and then every 4 cycles. For patients with lymph node involvement, scans were completed at baseline and upon clinical response or end of treatment, whichever occurred first. Results: Thirty-one patients received pralatrexate, with 18 (58%) men and median age of 57 yrs (range, 30-81). Patients had received a median of 6 prior therapies (range, 1-25). Cohorts at the following doses/schedules were enrolled: 30 mg/m2 x 3/4 weeks (n=2), 20 mg/m2 x 3/4 weeks (n=3), 20 mg/m2 x 2/3 weeks (n=7), 15 mg/m2 x 3/4 weeks (n=6), 15 mg/m2 x 2/3 weeks (n=3), and 10 mg/m2 x 3/4 weeks (n=10). Patients received pralatrexate for a median of 72 days (range, 7-491+); 4 patients received 〉10 cycles of treatment. The most common treatment-related adverse events (all grades) were mucositis (18 patients [58%]), nausea (14 patients [45%]), fatigue (14 patients [45%]), pyrexia (7 patients [23%]), vomiting (6 patients [19%]), anemia (6 patients [19%]), and edema (5 patients [16%]). Grade 3-4 treatment-related toxicities in 〉1 patient each were mucositis (4 patients [13%]) and anemia (2 patients [6%]). Mucositis was dose limiting (≥ grade 2) in 8 patients (26%). A total of 11 responses were observed, including 2 complete responses and 9 partial responses. In the 18 patients who received pralatrexate at a dose intensity of 15 mg/m2 x 3/4 weeks or greater, the objective response rate was 56% (10/18 patients). This appeared to be the threshold dose for substantial activity in CTCL, below which the incidence of responses decreased in this dose de-escalation trial. Conclusion: Pralatrexate shows impressive activity in the treatment of relapsed CTCL. The optimal dose and schedule that provided activity with tolerability for CTCL was determined to be pralatrexate 15 mg/m2 weekly on 3 of 4 weeks. This cohort is being expanded to better assess efficacy and durability. Disclosures: Horwitz: Allos Therapeutics, Inc: Consultancy, Research Funding. Duvic:Allos Therapeutics, Inc.: Research Funding. Lechowicz:Allos Therapeutics, Inc.: Consultancy. Fruchtman:Allos Therapeutics, Inc.: Employment.