scholarly journals Axial Vascularization of Nano-HA/Collagen/PLA Composites by Arteriovenous Bundle

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hai Wang ◽  
Xiao Chang ◽  
Guixing Qiu ◽  
Fuzhai Cui ◽  
Xisheng Weng ◽  
...  
Keyword(s):  
Autologous Bone Marrow ◽  
Bone Defects ◽  
Phase 2 ◽  
Large Defect ◽  
Group A ◽  
Group B ◽  
Axial Vascularization ◽  
Vascularized Bone ◽  
Av Bundle ◽  
Sufficient Oxygen

In previous studies, nano-hydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) composites have been prepared and confirmed to repair small sized bone defects. However, they are restricted to repair a large defect without sufficient oxygen and nutrition for cell survival. The result of this study confirmed that nHAC/PLA composites could be axially vascularized by being implanted intramuscularly with arteriovenous (AV) bundle (Group A) in the groins of rabbits. The combination with autologous bone marrow (Group B) could not enhance it the vascularization in early phase (2 weeks,P>0.05), but it could enhance in middle and later phases (6 and 10 weeks,P<0.01). It meant that nHAC/PLA could be prefabricated as a vascularized bone substitute for grafting.

scholarly journals Enhancement of VEGF on Axial Vascularization of Nano-HA/Collagen/PLA Composites: A Histomorphometric Study on Rabbits

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Xiao Chang ◽  
Hai Wang ◽  
Zhihong Wu ◽  
Xiaojie Lian ◽  
Fuzhai Cui ◽  
...  
Keyword(s):  
Control Group ◽  
Phase 2 ◽  
Histomorphometric Study ◽  
Group A ◽  
Group B ◽  
Axial Vascularization ◽  
Later Phase ◽  
Experimental Group ◽  
Av Bundle

The aim of this study was to investigate whether the nanohydroxyapatite/collagen/poly(L-lactic acid) (nHAC/PLA) composite is suitable to be compounded with VEGF to enhance the axial vascularization in vivo. Thirty rabbits were divided into 2 groups of 15 animals each. In control group, a nHAC/PLA scaffold slice was vascularized axially by an inserted ligated femoral arteriovenous (AV) bundle in the animal. In experimental group, a slice compounded with VEGF gel was applied. The rabbits were sacrificed at 2 weeks, 6 weeks, and 10 weeks after surgery; the specimens of scaffold slices underwent histomorphometric examination; analysis of the microvessel density (MVD) of both groups was done. The combination with VEGF (Group B) did not enhance the vascularization in early phase (2 and 6 weeks,P>0.05) but worked in later phase (10 weeks,P<0.05). The data of the experiment demonstrated the suitability of the nHAC/PLA composite as carrier for the growth factor VEGF, enabling its sustained release in bioactive form with enough binding efficacy.

Repairing Rabbit Radius Bone Defects with Simvastatin Compound Biological Bone

2021 ◽  
Vol 11 (7) ◽  
pp. 1263-1270
Author(s):  
Zhong-Yu Liu ◽  
Jin-Li Zhang ◽  
Yang Zhang ◽  
Shi-Lian Kan ◽  
Jun Liang ◽  
...  
Keyword(s):  
Bone Defect ◽  
Maximum Stress ◽  
Biomechanical Testing ◽  
Bone Defects ◽  
Bending Test ◽  
Bone Material ◽  
X Ray ◽  
Group A ◽  
Group B ◽  
Group D

Objective: This study aimed to investigate the feasibility of repairing rabbit radius bone defects with simvastatin compound biological bone. Methods: Simvastatin biological bone material was prepared, and osteoblasts were cultured. A total of 42 New Zealand white rabbits were randomly divided into four groups, and a bone defect with a length of 15 mm was created at the middle part of the radial shaft of both limbs in each rabbit, thereby establishing a bone defect model. The grafts in group A were biological bones of osteoblasts combined with simvastatin; the grafts in group B were biological bones of simvastatin; the grafts in group C were biological compound bones of osteoblasts; and the grafts in group D were simple biological bones. In each group, four animals were randomly sacrificed at the sixth and twelfth week after surgery, and specimens were collected for gross observation, X-ray examination, histological observation, and biomechanical testing. In each group, two animals were randomly sacrificed at the twelfth week after surgery; a three-point bending test was performed using a biomechanical testing machine, and the results were compared with those of a normal radius. Results: The X-ray and histological examinations at 6 and 12 weeks after surgery revealed that the osteogenesis ability of the simvastatin biological bone and osteoblast-simvastatin biological bone was better than that of the osteoblast biological bone and simple biological bone, which was superior in group A and group B to group C and group D. The results of the biomechanical examination revealed that the maximum stress of the normal radius was significantly higher than that of the experimental groups. Among the experimental groups, the difference between group A and group B was not statistically significant, and the maximum stress was higher in groups A and B than in groups C and D. Conclusion: Simvastatin biological bone material can promote the repair of rabbit radius defects and increase the quality of bone healing.

Phase 2 study of parsaclisib (INCB050465) for relapsed or refractory diffuse large b-cell lymphoma (DLBCL) (CITADEL-202).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19038-e19038 ◽  
Author(s):  
Morton Coleman ◽  
David Belada ◽  
René-Olivier Casasnovas ◽  
Rémy Gressin ◽  
Hui-Peng Lee ◽  
...  
Keyword(s):  
B Cell ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Phase 2 ◽  
Non Hodgkin Lymphoma ◽  
Phase 2 Study ◽  
Group A ◽  
Btk Inhibitor ◽  
Group B ◽  
General Physical

e19038 Background: Parsaclisib, a potent, highly selective, next-generation PI3Kδ inhibitor, showed preliminary efficacy as monotherapy for relapsed or refractory non-Hodgkin lymphoma, including DLBCL (Abstract 410, ASH 2017), in a phase 1/2 study. This phase 2 study further assessed parsaclisib in patients (pts) with relapsed or refractory DLBCL (NCT02998476). Methods: Pts enrolled into 2 groups (A, Bruton tyrosine kinase [BTK] inhibitor naïve; B, BTK inhibitor experienced) and received oral parsaclisib 20 mg QD for 8 wks, then 20 mg QW. In a planned interim futility analysis conducted in the first 40 pts treated in Group A, if ≤13 (≤32.5%) responded by IRC assessment, Group A was to be terminated. Results: At data cutoff (22 Jun 2018), 60 pts (Group A, n = 55; Group B, n = 5) were treated (median age, 71 y [range, 36—94]; men, 63.3%; ≥3 prior systemic therapies, 60%). At the planned interim analysis in Group A, ORR (by PET) was 25% (10/40 pts; 5 CMR, 5 PMR); the futility boundary was crossed. At data cutoff, ORR in Group A was 25.5% (14/55 pts; 8 CMR, 6 PMR); median PFS was 2.2 mo (95% CI: 2.0‒4.1); median DOR was 4.5 mo (95% CI: 2.1‒5.1). ORs were observed in germinal center B-cell (GCB) and non-GCB subtypes. ORR in Group B was 20% (1/5 pts; 1 CMR). The most common non-hematologic treatment-emergent adverse events (TEAEs) occurring in > 10% of all pts (all grade [Gr]; Gr 3/4) were rash events (21.7%; 1.7%), colitis/diarrhea events (16.7%; 5%), nausea (16.7%; 0%), cough (15%; 0%), and pyrexia (15%; 8.3%). Gr 3/4 AST and ALT elevations occurred in 5% and 1.7% of pts, respectively; Gr 3/4 neutropenia and anemia occurred in 5% of pts each. The most frequent ( > 5%) serious TEAEs were pyrexia (8.3%), general physical health deterioration (6.7%), and hypercalcemia (6.7%). TEAEs led to therapy discontinuation in 7 pts (2 treatment-related), dose interruption in 20 pts (10 treatment-related), and dose reduction in 3 pts (all treatment-related). Median duration of therapy was 57.5 d (range, 11–318). Conclusions: Parsaclisib monotherapy using a QD followed by QW dosing regimen was well tolerated with no new safety signals reported. Further evaluation of parsaclisib in all subtypes of DLBCL is ongoing in a combination study Clinical trial information: NCT02998476.

scholarly journals Lenalidomide and Low Dose Dexamethasone in Previously Treated Multiple Myeloma Patients with Impaired Renal Function: Efficacy Analysis of PrE1003, a Precog Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5712-5712
Author(s):  
Joseph Mikhael ◽  
Judi Manola ◽  
Sagar Lonial ◽  
Brendan M Weiss ◽  
Kurt Oettel ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Function ◽  
Renal Insufficiency ◽  
Research Funding ◽  
Impaired Renal Function ◽  
Response Rate ◽  
Phase 2 ◽  
25Mg Daily ◽  
Group A ◽  
Group B

Abstract Introduction: Lenalidomide (Len) and dexamethasone (dex) has proven to be a highly effective treatment for multiple myeloma (MM) and serves as the basis of other combinations in relapsed disease. However, nearly 1/3 of myeloma patients have renal insufficiency, and the optimal use of Len in this population is not well known. We undertook this study in 3 cohorts of pts: Group A had creatinine clearance (CrCl) of 30-60 ml/min, Group B with CrCl < 30 ml/min, and Group C, with CrCl < 30 ml/min and requiring dialysis. The Phase I component of the trial has been previously reported (ASCO 2014) demonstrating that full dose Len (25mg daily 21/28 days) can be given to all patients despite renal insufficiency, even when on dialysis. We now present data on response to treatment. Methods: In the Phase 2 component accrual was slow and the trial was terminated. However, prior to termination a modified exploratory analysis plan was established, including all 34 patients treated at the recommended phase 2 dose. This plan would declare the treatment worthy of further study if 18 or more of the 34 patients responded to treatment. This design had 84% power to distinguish a response rate of 60% from a null rate of 40%, using a 1-sided test with 10% type I error. Results: The Phase 2 efficacy cohort accrued 34 patients, consisting of 20 patients from Group A, 9 patients from Group B, and 5 patients from Group C. Response of PR or greater was seen in 17 patients, resulting in a 50% overall response rate (CI 37-63%). Treatment was well tolerated with expected adverse events; the most common adverse events were anemia, diarrhea, and fatigue. Eleven episodes of Grade 3 and one Grade 4 pneumonia were reported for 10 patients across all cohorts and dose levels; 3 were considered possibly related to treatment. Seventeen patients have remained on treatment for more than 12 cycles. In the exploratory analyses, median PFS was 7.5 months (95% CI, 3.6 - 19.7 months) and median OS was 19.7 months (95% CI, 10.4 - 42.5 months). Conclusions: Len Dex can be safely administered to patients with impaired renal function at full dose of 25mg daily 21/28 days, and is associated with a 50% response rate. Further investigation into other combinations with Len Dex in patients with renal impairment should be considered. Table Table. Disclosures Mikhael: Onyx: Research Funding; Sanofi: Research Funding; Abbvie: Research Funding; Celgene: Research Funding. Lonial:Merck: Consultancy; Novartis: Consultancy; Onyx: Consultancy; BMS: Consultancy; Onyx: Consultancy; Celgene: Consultancy; BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Millenium: Consultancy; Janssen: Consultancy. Weiss:Novartis: Consultancy.

scholarly journals Proposal for a new therapeutic high dosage of Pidotimod in children with Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome: an observational study.

2020 ◽  
Author(s):  
Sara Manti ◽  
Federica Filosco ◽  
Giuseppe Fabio Parisi ◽  
Giuseppe Germano Finocchiaro ◽  
Maria Papale ◽  
...  
Keyword(s):  
Adverse Events ◽  
Periodic Fever ◽  
Phase 1 ◽  
Aphthous Stomatitis ◽  
Potential Treatment ◽  
Phase 2 ◽  
Serious Adverse Events ◽  
Group A ◽  
Pfapa Syndrome ◽  
Group B

Abstract Background. Despite to PFAPA syndrome is considered a benign and self-limited condition in childhood its impact on patients and families can be remarkable in many cases. Currently, the therapeutic options for managing are non-specific and no consensus exists about the best treatment to use. Pidotimod has been suggested as a new potential treatment in PFAPA syndrome for its immunodulatory effects. We conducted a preliminary, prospective, controlled, open, cross-over trial to assess the efficacy and the safety of Pidotimod in the treatment of children with PFAPA syndrome.Methods. 22 children with PFAPA syndrome were randomly allocated to treatment with Pidotimod (with 2 vials of 400 mg daily) in combination with betamethasone 0.5-1 mg on need (group A) or betamethasone 0.5-1 mg on need (group B). Each treatment period was for 3 months (Phase 1), after that patients were switched to the other arm for other 3 months (Phase 2). Efficacy was expressed in terms of number of episodes of fever, tonsillitis, and aphthous stomatitis, as well as the additional use of betamethasone on need. Safety and tolerability of the Pidotimod were evaluated on the basis of the number and type of adverse events (AEs) recorded during the treatment.Results. Patients receiving Pidotimod and betametasone showed a significant decrease in frequency of fevers (p = 0.002); number of episodes of tonsillitis (p = 0.049); aphthous stomatitis (p = 0.036) as well as the betamethasone use on need (p = 0.007). Overall, 19/22 (86.4%) showed benefits from Pidotimod administration. The safety profile of Pidotimod was excellent as no serious adverse events have been reported in the treated groups.Conclusions. We firstly showed that high dosage of Pidotimod is an effective and safe to reduce the PFAPA attacks in children.

scholarly journals EFFECTS OF DIETARY CHELATED AND SEQUESTERED ZINC AND ZINC SULFATE ON GROWING LAMBS FED A PURIFIED DIET

1977 ◽  
Vol 57 (1) ◽  
pp. 93-99 ◽  
Author(s):  
S. K. HO ◽  
M. HIDIROGLOU
Keyword(s):  
Zinc Sulfate ◽  
Phase 1 ◽  
Marked Change ◽  
Feed Consumption ◽  
Zinc Status ◽  
Plasma Zinc ◽  
Phase 2 ◽  
Group A ◽  
Two Phases ◽  
Group B

Sixteen crossbred wethers were divided into four groups and fed a purified diet deficient in zinc. The experiment consisted of two phases, each of a 6-wk duration. During phase 1, groups A and B were supplemented with 0 or 50 ppm of zinc, as zinc sulfate, and groups C and D with 5 ppm of zinc in chelated and sequestered form, respectively. In phase 2, the animals received the same supplemental sources of zinc, but the levels fed to groups A, B, C and D were changed to 25, 5, 25 and 25 ppm, respectively. Group A developed typical signs of zinc deficiency as early as wk 3 of phase 1, while group B showed deficiency signs at the end of phase 2. Neither group C nor D showed any overt deficiency signs at any time during the experiment. Both chelated and sequestered zinc at 5 ppm (groups C and D, phase 1) resulted in lowered zinc status, in terms of plasma zinc and plasma alkaline phosphatase activity, but rates of feed consumption and weight gain comparable to those of the zinc sufficient animals (group B, phase 1) were maintained. Feeding 25 ppm of supplemental chelated or sequestered zinc to the respective groups after they had received 5 ppm for 6 wk did not result in any marked change in feed consumption or growth trends. Animals fed 25 ppm of chelated or sequestered zinc had less hepatic zinc than those fed the same level of zinc, as the sulfate. In all responses examined, no significant differences were observed between chelated and sequestered zinc.

scholarly journals Novel piston technique versus Ilizarov technique for the repair of bone defect after lower limb infection

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jiafei Du ◽  
Zifei Yin ◽  
Pengfei Cheng ◽  
Pei Han ◽  
Hao Shen
Keyword(s):  
Bone Healing ◽  
Lower Limb ◽  
Joint Stiffness ◽  
Functional Results ◽  
Bone Defects ◽  
Ilizarov Technique ◽  
Group A ◽  
The Mean ◽  
Group B

Abstract Background We aimed to compare the effectiveness and complications of a novel piston technique versus the Ilizarov technique for the repair of bone defects after lower limb infection. Patients and methods We retrospectively reviewed 41 patients who had been treated at our department for lower extremity bone defects following osteomyelitis. There were 38 men and three women with a mean age of 43.41 (range, 12–69 years). The infected bone defects involved 36 tibias and five femurs. The piston technique (PT, group A) was used in 12 patients and the Ilizarov technique (IT, group B) in 29 patients. The mean follow-up period was 28.50 months (PT) and 29.90 months (IT). The modified Application of Methods of Illizarov (ASAMI) criteria was used to evaluate bone healing and functional recovery. Results Complete eradication of the infection and union of docking sites were accomplished in both groups. The mean external fixator index (EFI) was 42.32 days/cm in group A versus 58.85 days/cm in group B (p < 0.001). The bone outcomes were similar between groups A and B (p = 0.558) (excellent [9 vs. 19], good [3 vs.10]); group A showed better functional outcomes than group B (p < 0.05) (excellent [7 vs. 6], good [4 vs. 12], fair [0 vs. 10] and poor [1 vs. 1]). Pain was the most common complaint during follow-up, and group A had fewer cases of pin tract infection (1 vs. 6), adjacent joint stiffness (3 vs. 8), and delayed healing of the joint (0 vs. 3). Conclusions Satisfactory bone healing can be achieved by using both PT and IT, although PT demonstrated better functional results, lower EFI, and allowed early removal of the external fixation. We found that this novel piston technique can improve the comfort of patients, reduce the incidence of complications, and provide rapid and convenient rehabilitation.

scholarly journals Results of the Study of Bone Tissue Density in Patients of the Study Groups at the Restoration of Bone Defects by Various Osteoplastic Materials

2021 ◽  
Vol 6 (2) ◽  
pp. 158-162
Author(s):  
A. V. Bambuliak ◽  
◽  
N. B. Kuzniak ◽  
R. R. Dmitrenko ◽  
S. V. Tkachik ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Bone Density ◽  
Bone Tissue ◽  
Bone Defect ◽  
Maxillofacial Surgery ◽  
Bone Defects ◽  
X Ray ◽  
Group A ◽  
X Ray Computed ◽  
Group B

The restoration processes of damaged or lost bone tissue are an important and topical issue of surgical dentistry and maxillofacial surgery today. According to statistics, diseases that are accompaning by destructive changes in bone tissue occupy one of the dominant places among the nosologies of MFA. Along with the use of updated methods of surgical technique, both before and now the problem of choice of bone-plastic material is relevant, because it is known that osteoplasty opens up great opportunities for complete rehabilitation of patients. The purpose of the study was to determine the effectiveness of our developed osteoplastic composition for the restoration of bone defects in dentistry. Materials and methods. X-ray computed tomography to determine bone density was performed in 26 patients with bone defect replacement "Kolapan-L" (group A), 28 people during augmentation of our proposed osteoplastic composition "Kolapan-L" + multipotent mesenchymal stromal cells + platelet-rich plasma) (group B), and 25 patients where the healing of the bone defect occurred spontaneously (group B). X-ray computed tomography was performed on a 16-slice spiral computed tomography Siemens Somatom Emotionc. Image processing was performed using the program "Dicom". Statistical processing of research results was carried out using conventional methods of variation statistics. Results and discussion. After 1 year of research, the average value of the bone density in patients of group B was probably higher: 1.5 times and 1.8 times relative to the corresponding data in groups A and B. At the same time, the minimum value of the bone density in patients of subgroups A and B was 1.5 times and 1.8 times lower than in persons of group B (p <0.01, p1 <0.01). At the same time, the maximum values of the bone density in patients of group B, where the augmentation of bone defects was performed using our proposed composition, were 1.4 times (p <0.01) and 1.8 times (p <0.05, p1 <0.01) higher than in group A, in the replacement of bone defects "Kolapan-L" and in group B, where the healing of the bone defect was spontaneous, respectively. It was found that in patients of group B after 12 months of studies, the average density of osteoregeneration was 1036.69±55.53 (HU), which was 1.5 times and 1.8 times more than in group A (p <0.01) and in group B patients (p <0.05, p1 <0.01) respectively. Conclusion. The use of tissue equivalent of bone tissue, proposed by us to replace a bone defect based on multipotent mesenchymal adipose tissue cells, contributed to the maximum increase in bone density, with a slightly lower effect of increasing bone density in the augmentation of bone defects

scholarly journals Comparative Study on the Application of Mesenchymal Stromal Cells Combined with Tricalcium Phosphate Scaffold into Femoral Bone Defects

2018 ◽  
Vol 27 (10) ◽  
pp. 1459-1468 ◽  
Author(s):  
Pavel Šponer ◽  
Tomáš Kučera ◽  
Jindra Brtková ◽  
Karel Urban ◽  
Zuzana Kočí ◽  
...  
Keyword(s):  
Stromal Cells ◽  
Tricalcium Phosphate ◽  
Bone Defects ◽  
Control Group ◽  
Graft Material ◽  
Synthetic Graft ◽  
Group A ◽  
Group B ◽  
And Control

This prospective study sought to evaluate the healing quality of implanted ultraporous β-tricalcium phosphate sown with expanded autologous mesenchymal stromal cells (MSCs) into femoral defects during revision hip arthroplasty. A total of 37 osseous defects in 37 patients were treated and evaluated concerning bone regeneration. Nineteen subjects received β-tricalcium phosphate graft material serving as a carrier of expanded autologous MSCs (the trial group A), nine subjects received β-tricalcium phosphate graft material only (the study group B) and nine subjects received cancellous allografts only (the control group C). Clinical and radiographic evaluations were scheduled at 6 weeks, 3, 6, and 12 months post-operatively, and performed at the most recent visit as well. All observed complications were recorded during follow-up to assess the use of an ultraporous β-tricalcium phosphate synthetic graft material combined with expanded MSCs in bone defect repair. The resulting data from participants with accomplished follow-up were processed and statistically evaluated with a Freeman–Halton modification of the Fischer’s exact test, a P < 0.05 value was considered to be significant. Whereas no significant difference was observed between the trial group A with β-tricalcium phosphate synthetic graft material serving as a carrier of expanded autologous MSCs and control group C with cancellous impaction allografting in terms of the bone defect healing, significant differences were documented between the study group B with β-tricalcium phosphate graft material only and control group C. Regarding adverse effects, six serious events were recorded during the clinical trial with no causal relationship to the cell product. β-tricalcium phosphate synthetic graft material serving as a carrier of expanded autologous MSCs appears safe and promotes the healing of bone defects in a jeopardized and/or impaired microenvironment. This clinical trial was registered at the EU Clinical Trials Register before patient recruitment (Registration number: EudraCT number 2012-005599-33; Date of registration: 2013-02-04).

Pralatrexate and Gemcitabine in Patients with Relapsed or Refractory Lymphoproliferative Malignancies: Phase 1 Results.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1674-1674 ◽  
Author(s):  
Steven M. Horwitz ◽  
Julie M. Vose ◽  
Ranjana Advani ◽  
Kamalesh Sankhala ◽  
Swaminathan Padmanabhan ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
B Cell Lymphoma ◽  
Phase 2 ◽  
Large B Cell Lymphoma ◽  
Group A ◽  
Refractory Lymphoma ◽  
Group B

Abstract Abstract 1674 Poster Board I-700 Background Pralatrexate is a new anti-folate with increased affinity for the reduced folate carrier 1 (RFC-1) and longer intracellular retention in tumor cells due to efficient polyglutamation by folylpolyglutamyl synthetase (FPGS). Pralatrexate and gemcitabine each have activity as monotherapy in patients with relapsed or refractory lymphoma. Preclinical data reported synergy for the combination in NHL cell lines and xenografts that was schedule dependent (pralatrexate followed by gemcitabine) (Clin Cancer Res 2006;12:924-932). We initiated a multi-center Phase 1/2a study (PDX-009; NCT00481871) to evaluate this treatment combination. The primary objective of the Phase 1 portion was to determine the maximum tolerated dose (MTD) and optimal Phase 2 dose and schedule for the combination of pralatrexate and gemcitabine in patients with relapsed or refractory lymphoma. Methods Eligibility criteria included histologically confirmed lymphoma, progressive disease after ≥1 prior treatment and ECOG performance score 0-2. Patients in group A (n=7) received pralatrexate on day 1 and gemcitabine on day 2, once weekly for 3/4 wks. Patients in group B (n=10) also received pralatrexate and gemcitabine on sequential days, but were treated only every 2 wks (q2w). Patients in group C (n=17) received pralatrexate followed 1h later by gemcitabine on the same day q2w. All patients received vitamin B12 and folic acid supplementation. Prior gemcitabine exposure was permitted. Results As of May 2009, 34 patients were treated in Phase 1, including 24 men (71%), and median age was 63 years (range, 19-81). Histology included 13 patients with B-cell lymphoma, 11 with T/NK-cell lymphoma, 7 with Hodgkin's lymphoma, and 3 with “other” lymphoma. Patients had received a median of 3.5 prior regimens (range 1-11). All patients with once-weekly sequential-day dosing (pralatrexate 10-15 mg/m2 and gemcitabine 300-400 mg/m2) in Group A had dose-limiting toxicities (DLTs) of thrombocytopenia and/or neutropenia; therefore accrual to this schedule was halted and subsequent cohorts received pralatrexate with gemcitabine on the q2w schedule (groups B and C). The MTD with the q2w dosing schedule was pralatrexate/gemcitabine 10/400 mg/m2 when given on sequential days (group B) and 15/600 mg/m2 when given on the same day (group C). The DLTs for group B were cellulitis, pulmonary embolus, thrombocytopenia, and febrile neutropenia and the DLTs for Group C were fatigue, hypoxia, mucositis, and thrombocytopenia. Across all groups, the most frequently reported Gr 3-4 pralatrexate-related adverse events were neutropenia (41%), thrombocytopenia (35%), anemia (29%), and leukopenia (12%). Of 33 patients who were evaluable for response, 7 (21%) showed partial response, including patients with Hodgkin's lymphoma (4), diffuse large B-cell lymphoma (1), angioimmunoblastic T-cell lymphoma (1), and composite diffuse large B-cell lymphoma and T-cell lymphoma (1). Responses were seen in patients treated on the same day as well as the sequential day schedules. Conclusion Treatment with pralatrexate and gemcitabine is feasible, with acceptable toxicity, when administered on a q2w schedule. However, the MTD of each drug is 50% greater when given on the same day as compared to treating on sequential days. Preliminary results show activity of the combination of pralatrexate and gemcitabine in lymphoid malignancies with a 21% response rate in this heavily pretreated population. Phase 2 expansions at the MTD will explore both sequential-day dosing (10/400 mg/m2) and same-day dosing (15/600 mg/m2) in a q2w schedule. Disclosures Horwitz: Allos Therapeutics, Inc: Consultancy, Research Funding. Advani:Allos Therapeutics, Inc: Research Funding. Fruchtman:Allos Therapeutics, Inc.: Employment.

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