Safety of Clofarabine with Multiagent Chemotherapy in Childhood High Risk Relapse of Acute Lymphoblastic Leukemia (Vandevol study of the French SFCE Acute Leukemia Committee).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2570-2570
Author(s):  
Brigitte Nelken ◽  
Guy Leverger ◽  
Claire Galambrun ◽  
Genevieve Plat ◽  
Claudine Schmitt ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Level ◽  
Bacterial Infections ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Off Label Use ◽  
Childhood All ◽  
Off Label ◽  
Post Transplant ◽  
Label Use

Abstract Abstract 2570 Background. Current outcome of very early relapse of ALL in children remains poor. Clofarabine, a novel nucleoside analog has proven effective as a single agent in childhood ALL second relapse, providing a CR+CRp ratio of 20 to 28 % (Jeha 2006, Kearns 2006). Clofarabine in combination with cyclophosphamide and Etoposide provided a 44% overal response rate rate in children with advanced ALL (Hijiya 2011) and further multi-drug combinations need to be investigated. The VANDA regimen that has proven effective in high risk ALL and in ALL relapse (Domenech 2008) was used as a template, Cytarabine being replaced by Clofarabine in this combination. Procedure. A phase I study combining escalating doses of Clofarabine with fixed doses of Mitoxantrone, Etoposide, Asparaginase and Dexamethasone was undertaken in children presenting very early (18 months or less after initial diagnosis) medullary or combined ALL relapse or children with second relapse or post transplant relapse. A 3+3 rolling design was used for escalating clofarabine doses with 25% increments from 20 to 40mg/m2/d. Results. Sixteen patients were enrolled, eleven in first marrow relapse, four in second relapse. One patient with an initially refractory disease was secondary excluded as he didn't fulfill the inclusion criteria. Four patients had previously been allografted. Three patients were enrolled at dose level 1 (clofarabine 20 mg/m2), and 3 patients at dose level 2 (clofarabine 26 mg/m2) without any significant dose-limiting toxicity (DLT). Six patients were enrolled at dose level 3 (clofarabine 32 mg/m2), one patient experienced a liver DLT (gamma GT elevation) exceeding 7 days. At the last planned dose level (clofarabine 40 mg/m2), two patients had a grade 3 transaminase elevation exceeding 7 days and 2 patients had a severe fungal infection. Median duration of neutropenia was 20 days (15–31). Other expected toxicities included 3 documented bacterial infections, 3 mucosal toxicities needing parenteral support, one lung aspergillosis, one transient insulin dependant hyperglycemia. There was no toxic death. Out of 15 evaluable patients, 11 (73%) achieved a complete cytological remission (CR). 4 relapses occurred at 1, 1, 2 and 3 months. 6 patients proceeded to allo-SCT with 2 second allografts. One allografted patient died from EBV-PTLD, the others are alive at 2, 13, 13, 15, and 29 months post-transplant. Conclusion. Clofarabine in combination with four major antileukemic drugs appeared feasible and effective in inducing complete remission in those high risk patients. Clofarabine MTD was 32 mg/m2/d for five days and this dose step is currently being expanded to a total of 10 patients, before a phase II study will be proposed for early and very early ALL relapses. Study registered at ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT01279096). Disclosures: Off Label Use: off label use of clofarabine.

Alemtuzumab-Containing Allogeneic Hematopoietic Cell Transplant (HCT) for Relapsed Lymphomas: Prognostic Factors and Outcome.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2247-2247
Author(s):  
Vaishalee P. Kenkre ◽  
Sarah Horowitz ◽  
Sonali M. Smith ◽  
Andrew Artz ◽  
Kenneth S. Cohen ◽  
...  
Keyword(s):  
B Cell ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
Low Grade ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Off Label Use ◽  
Off Label ◽  
Allogeneic Hct ◽  
Label Use

Abstract Abstract 2247 Poster Board II-224 The role of allogeneic HCT for relapsed lymphomas remains imprecisely defined. Most pts considered for alloHCT are heavily pretreated and many have failed a prior autologous HCT. At The University of Chicago, 69 lymphoma pts (median age 54; range, 24-70) underwent allogeneic HCT after alemtuzumab-containing reduced intensity conditioning (RIC) regimens between 11/01 and 6/09. Ten had Hodgkin lymphoma (HL), 23 low-grade B-cell NHL (LGL), 17 intermediate-grade B-cell NHL (IGL), 9 mantle cell lymphoma (MCL), and 10 T-cell NHL (TCL). 25 pts (36%) had refractory disease and 17 pts (25%) had elevated LDH. Pre-HCT PET scans were performed in 48 pts and 31 (65%) were PET positive. Performance status (PS) was 0 for 45 pts (70%) and 1 for 18 pts (28%). 19 pts (27%) had failed a prior autologous transplant, and 4 pts had failed a prior allogeneic transplant. 31 pts (45%) had unrelated and 38 (55%) related donors. Conditioning regimens along with alemtuzumab included: fludarabine/melphalan (n = 40), clofarabine/melphalan (n = 20), fludarabine/busulfan (n = 5), and thiotepa/busulfan/cyclophosphamide (n = 4). GVHD prophylaxis consisted of single agent tacrolimus in all patients. With a median follow-up for survivors of 22 mos (range 2-94 mos), 2 yr overall survival (OS) is 53% (95%CI, 40-66). Progression-free survival (PFS) is 46% (95%CI, 34-58) at 1 yr and 38% (95%CI, 28-50) at 2 yrs. 11 pts had grade II-IV aGVHD and transplant-related mortality (TRM) was 20% at 1 yr. Disease responsiveness to salvage chemotherapy prior to transplant (as determined by CT scan) was highly predictive of PFS (p = 0.03). Pts with chemo-sensitive disease had a 2 yr PFS of 44% (95%CI, 28-60), those with chemo-refractory disease 30% (95% CI, 10-50). 2 yr PFS was 52% (95%CI, 30-74%) for LGL, 48% (95%CI, 12-84) for MCL, 28% (95%CI, 6-50) for IGL, 30% (95%CI, 0-60) for HL, and 34% (95%CI, 6-66) for TCL. Patient age, pre-transplant LDH, PS (0 vs 1), prior auto, donor type, and conditioning regimen did not correlate with outcome. Interestingly, a positive vs negative pre-HCT PET also did not correlate with outcome (p = 0.21). 23 pts (33%) relapsed. 13 of those have died, 2 are alive with disease, and 8 are in a durable subsequent remission lasting a median of 46 mos (range 8-69) after further chemotherapy (n=6) or DLI (n=2). Durable subsequent remissions were more common in those with late relapses (>6 mos after transplant) (Fig 1). Conclusion: Chemosensitivity by conventional CT scans remains the most important predictor of outcome. In contrast to other reports, neither the pre-HCT PET nor LDH correlate with outcome. Patients relapsing > 6 mos after alloHCT can re-enter durable remissions with chemotherapy alone. This suggests a favorable interaction between a persisting donor graft and salvage chemotherapy. Disclosures: Off Label Use: off-label use of clofarabine and alemtuzumab. Kline:Genzyme corporation: Membership on an entity's Board of Directors or advisory committees. Stock:Genzyme: Research Funding.

scholarly journals Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research

2015 ◽  
Vol 20 (3) ◽  
pp. 186-196 ◽  
Author(s):  
Angela S. Czaja ◽  
Pamela D. Reiter ◽  
M. Lynn Schultz ◽  
Robert J. Valuck
Keyword(s):  
Intensive Care ◽  
High Risk ◽  
Pediatric Intensive Care ◽  
Future Research ◽  
Off Label Use ◽  
Off Label ◽  
Lengths Of Stay ◽  
Uncertain Evidence ◽  
Organ Failures ◽  
Label Use

OBJECTIVES: To characterize off-label prescribing among US pediatric intensive care units (PICUs), determine characteristics associated with off-label use, and identify medications in highest need for additional study. METHODS: Medications prescribed for ≥1% PICU patients (age < 18 years) in 2010 were identified from 39 children's hospitals. Use in a patient younger than the Food and Drug Administration (FDA)-approved age for any indication was considered off-label. Hierarchical multivariable modeling was used to identify characteristics associated with off-label use, accounting for center effects. Highest-impact drugs were defined by: 1) high off-label use (off-label use in at least 5% of the PICU cohort), 2) high risk medication, and 3) high priority status by the FDA or Best Pharmaceuticals for Children Act (BPCA). RESULTS: A total of 66,896 patients received ≥1 medication of interest (n = 162) during their PICU stay. A median of 3 (interquartile range, 2–6) unique drugs per patient were used off-label. Those who received ≥1 drug off-label (85% of the cohort) had longer median PICU (2 days vs 1 day) and hospital (6 days vs 3 days) lengths of stay and higher mortality (3.6% vs 0.7%), p < 0.001. Factors independently associated with off-label drug use included: age 1 to 5 years, chronic conditions, acute organ failures, mechanical ventilation, arterial or venous catheters, dialysis, and blood products. Half of prescribed medications (n = 84) had been used off-label: 26 with significant off-label use, 30 high-risk medications, and 47 with high FDA/BPCA priority. The highest impact medications identified were: dexmedetomidine, dopamine, hydromorphone, ketamine, lorazepam, methadone, milrinone, and oxycodone. CONCLUSIONS: Most PICU patients are exposed to off-label medication use, with uncertain evidence. Future medication research in this population should focus on medications with high impact potential.

Phase I-II Study of Fludarabine, Cytarabine and Oxaliplatin In Patients with Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4274-4274
Author(s):  
Apostolia Maria Tsimberidou ◽  
Michael J Keating ◽  
Elihu H. Estey ◽  
Elias Jabbour ◽  
Patrick Zweidler-McKay ◽  
...  
Keyword(s):  
High Risk ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Myeloid Leukemia ◽  
Off Label Use ◽  
Off Label ◽  
Grade 3 ◽  
Acute Myeloid ◽  
Refractory Aml

Abstract Abstract 4274 Introduction: The prognosis of patients with relapsed or refractory acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) is dismal. We designed a Phase I-II combination therapy of fludarabine, cytarabine and oxaliplatin (FAO) for patients with relapsed/refractory AML or high-risk MDS, hypothesizing that a mechanistic interaction of these agents combined would increase the leukemic cell death. Patients and Method: FAO consisted of fludarabine 30mg/m2 IV (Days 2–6); cytarabine 500mg/m2 IV continuous infusion (Days 2–6); and escalating doses of oxaliplatin (20, 25, 30 or 35mg/m2/day IV) (Days 1–4) (phase I). Patients received antibacterial, antiviral, antinausea and tumor lysis prophylaxis. Treatment was given every 28 days. Dose limited toxicity (DLT) was defined as any ≥ grade 3 non-hematological toxicity lasting ≥ 3 days involving a major organ system (brain, heart, kidney, liver, or lung). The maximum tolerated dose of oxaliplatin was used in the phase II portion of the study. The study was conducted based on an outcome-adaptive Bayesian procedure (Thall and Cook) and using the program “efficacy toxicity dose finding” (MD Anderson, Department of Biostatistics website). Results: Twenty-seven patients were treated: phase I, n=12 (3 patients per oxaliplatin dose level); and phase II, n=15. The median age was 58 years (range, 6–71). Six patients were ≥ 65 years. There were 11 men and 16 women. Six patients had performance status (PS) 0, 16 had 1 and 5 patients had PS 2. Twenty-one patients had complex cytogenetics (CG), 3 normal and 3 hyperdiploid. All patients were pretreated, including 11 patients who had prior allogeneic stem cell transplantation (SCT). DLTs were Grade 3 transaminitis; Grade 3 hyperbilirubinemia; and Grade 3 renal insufficiency and were all noted at the 35mg/m2/d oxaliplatin dose level. Therefore, the phase II recommended dose of oxaliplatin was 30 mg/m2/day. No DLT was noted in 18 patients treated at oxaliplatin 30 mg/m2/day dose level. Grade 3–4 non-hematologic toxicity was noted as follows: diarrhea (4 of 27 patients), hyperbilirubinemia (3 of 27 patients) and transaminitis (3 of 27 patients). Five of 27 (18.5%) patients responded to FAO (CR, n=3; CRp, n=2). Three of the 5 responders had prior SCT. Characteristics and clinical outcomes of responders are shown in Table: Conclusion: The Phase II recommended dose of FAO was fludarabine 30mg/m2 IV (Days 2–6); cytarabine 500mg/m2 IV continuous infusion (Days 2–6); and oxaliplatin 30mg/m2/day IV (Days 1–4) and it was well tolerated. FAO had significant antitumor activity in selected patients with heavily pretreated relapsed or refractory poor-risk AML and warrants further investigation. Disclosures: Tsimberidou: Sanofi: Research Funding. Off Label Use: Oxaliplatin - off-label use in a Phase I-II clinical trial (combined with fludarabine and cytarabine) for patients with relapsed/refractory AML or high-risk MDS.

Improved Outcome with ATRA-Arsenic Trioxide Compared to ATRA-Chemotherapy in Non-High Risk Acute Promyelocytic Leukemia – Updated Results of the Italian-German APL0406 Trial on the Extended Final Series

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 12-12 ◽  
Author(s):  
Uwe Platzbecker ◽  
Giuseppe Avvisati ◽  
Gerhard Ehninger ◽  
Laura Cicconi ◽  
Christian Thiede ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Research Funding ◽  
Primary Study ◽  
Intermediate Risk ◽  
Off Label Use ◽  
Front Line ◽  
Off Label ◽  
Label Use ◽  
Line Management

Abstract Background: We recently showed that the combination of ATRA and arsenic trioxide (ATO) is at least not inferior and possibly superior to standard ATRA and chemotherapy (CHT) in the front-line management of low/intermediate risk APL (Italian-German APL 0406 trial; Lo-Coco et al., NEJM 2013). We report herein on the extended and final series of 276 patients (162 were in the previous report) with the last case being enrolled into the study in January 2013. Methods: The APL0406 study was a prospective, open-label, randomized intergroup trial conducted by the Italian GIMEMA and the German SAL and AMLSG study groups. Eligible patients were adults aged 18-<71 years with newly diagnosed, genetically confirmed, non-high-risk (WBC≤10x109/L) APL. Patients were randomized to receive the ATO+ATRA combination originally developed by the MD Anderson Cancer Center group, or the Italian AIDA2000 protocol (Estey et al., Blood 2006 and Lo-Coco et al., Blood 2010). Patients in the ATRA-ATO arm received ATO 0.15/kg plus ATRA 45 mg/m2 daily until CR, then ATO 5 days/week, 4 weeks on 4 weeks off, for a total of 4 courses and ATRA 2 weeks on and 2 weeks off for a total of 7 courses. Patients in the ATRA-CHT arm received the standard AIDA (ATRA+Idarubicin) induction followed by 3 cycles of anthracycline-based consolidation together with ATRA and low dose CHT and ATRA for maintenance. The primary study objective was EFS at 2 years. Results: A total of 254 patients were evaluable for response to induction. CR was achieved in 122/122 (100%) in the ATRA-ATO versus 128/132 (97%) in the ATRA-CHT arm (P=0.12). Four patients died during induction in the ATRA-CHT arm. After a median follow-up of 36 months (range 1-75 months), the 2-year EFS was 98% and 84.9% in the ATRA-ATO and ATRA-CHT groups respectively (P= 0.0002), The 2-year cumulative incidence of relapse (CIR) rate was 1.1% and 9.4%, respectively (P=0.005) and, finally, the 2-year overall survival (OS) rate was 99.1% vs. 94.4% (P=0.01) for ATRA-ATO vs ATRA-CHT, respectively. Conclusions: The data on this extended cohort demonstrate a significantly augmented survival benefit coupled to a higher antileukemic efficacy provided by ATRA-ATO as compared to ATRA-CHT, in low/intermediate risk APL. These results further support ATRA-ATO as the new standard of care in this clinical setting. Figure 1 Figure 1. Disclosures Platzbecker: Teva: Honoraria. Off Label Use: Presentation includes off-label use of arsenic trioxide (ATO) in front-line management of APL. ATO is currently approved in treatment of relapsed APL in the US and Europe. Breccia:Bristol Myers Squibb: Consultancy; Novartis: Consultancy. Fiedler:TEVA: Travel reimbursement for meeting attendance Other. Lübbert:Cephalon / TEVA: Travel support Other. Link:TEVA: Consultancy, Speakers Bureau. Radsak:Celgene: Research Funding. Döhner:TEVA: Research Funding. Schlenk:TEVA: Research Funding, Speakers Bureau. Lo-Coco:TEVA: Honoraria; Lundbeck: Honoraria.

Survival outcomes and practice trends for off-label use of adjuvant targeted therapy in high-risk locoregional renal cell carcinoma

2020 ◽  
Vol 38 (6) ◽  
pp. 604.e1-604.e7 ◽  
Author(s):  
Nicholas H. Chakiryan ◽  
Ann Martinez Acevedo ◽  
Mark A. Garzotto ◽  
Yiyi Chen ◽  
Jen-Jane Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survival Outcomes ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

Response to Dasatinib In Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Correlates with p-Lyn and p-Syk

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2457-2457
Author(s):  
Philip C. Amrein ◽  
Eyal C Attar ◽  
Tak Takvorian ◽  
Ephraim Hochberg ◽  
Karen K Ballen ◽  
...  
Keyword(s):  
Clinical Response ◽  
Failure Time ◽  
Single Agent ◽  
Clinical Results ◽  
Off Label Use ◽  
Off Label ◽  
Lyn Kinase ◽  
Grade 3 ◽  
Label Use

Abstract Abstract 2457 Background: Preclinical studies have shown that CLL cells overexpress Lyn kinase, and in vitro inhibition of Lyn kinase leads to apoptosis of the CLL cells (Contri, J Clin Invest 2005). In 2007, based on this evidence, we initiated a phase II study in patients with previously treated CLL/SLL using dasatinib as a single agent. Preliminary clinical results of this study were reported in 2008. Methods: Patients were required to be over 18 years of age, have a pathologically confirmed diagnosis of CLL/SLL by flow cytometry or immunohistochemistry, and have failed either 1 course of treatment with a fludarabine-containing regimen or 2 non-fludarabine containing regimens. The starting dose of dasatinib was 140 mg daily by mouth. In the first week of therapy sequential blood samples were tested for Lyn kinase protein, p-Lyn, Syk protein, p-Syk, indicators of apoptosis (caspase 3 and Tunel assay), and gene expression profiling among the 3 patients that agreed to participate in this aspect of the study. The final clinical results, with over 1 year follow-up of all patients, showed that among the 15 patients enrolled the major toxicity encountered was myelosuppression: grade 3 + 4 neutropenia in 10 subjects and grade 3 + 4 thrombocytopenia in 6 subjects. Other toxicities included one subject with grade 3 diarrhea, 2 patients with grade 2 pleural effusions, and 1 patient had a transiently prolonged QTc of 516 ms. There were no fatal events, and all toxicities were reversible. In the final analysis partial responses (PR) by NCI-WG criteria were achieved in 3 of the 15 patients (20% with 90% CI 6%-44%). An additional 1 patient would have qualified for an NCI-WG PR except for myelosuppression. Among the 15 patients, 9 had nodal responses (2 CR and 7 PR) by physical exam (PE), 5 without a 50% reduction in lymphocytosis. CT scans confirmed nodal responses in 4 of the 9 patients. Among the 5 patients with del (11q), all 5 had nodal responses by PE. The median time to treatment failure, time to progression, and overall survival were 6.7 months, 7.5 months, and 27 months, respectively. The relationships between clinical response, Lyn kinase, Syk kinase, and apoptosis were analyzed using mononuclear cells from 3 patients at baseline, and at 3, 6, and 24 hours after dosing with dasatinib. For the one of these 3 patients that responded to dasatinib, the high baseline level of p-Lyn was dramatically suppressed at 6 hours correlating with suppression of p-Syk. For the other 2 patients, who did not have a clinical response, there was minimal suppression of p-Lyn and no suppression of p-Syk at 6 hours. Microarray analysis of mRNA from these samples showed that within 6 hours there was significant (p<.05) down-regulation of genes for spleen tyrosine kinase, FK506 binding protein, early growth response 1, NLR family CARD 3, and NOTCH, while genes for GNAS and NFKB2 were up-regulated. Conclusions: While our in vitro data is very preliminary, it suggests that the activity of dasatinib in CLL may result from the suppression of p-Lyn and inhibition of p-Syk. Disclosures: Amrein: Bristol-Myers Squibb: Honoraria. Off Label Use: Dasatinib used in CLL is off-label use. We show that some patients have a clinical response to the drug in this setting.

Multicenter Phase I Trial of Intraventricular Immuno-Chemotherapy in Recurrent CNS Lymphoma

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 959-959
Author(s):  
James L. Rubenstein ◽  
Lingjing Chen ◽  
Ranjana Advani ◽  
Jan Drappatz ◽  
Elizabeth Gerstner ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase I ◽  
Dose Level ◽  
Intraventricular Injection ◽  
Cns Lymphoma ◽  
Cell Transplant ◽  
Off Label Use ◽  
Off Label ◽  
Dose Levels ◽  
Label Use

Abstract Abstract 959 Background: We recently studied the safety and activity of intraventricular rituximab monotherapy in the treatment of recurrent intraocular and CNS non-Hodgkin lymphoma (NHL) (JCO 2007 25: 1350–1356). Rapid dissemination throughout the craniospinal axis was demonstrated and cytologic responses were detected in six out of ten patients. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. The major goals of this current trial are to perform the first study of intraventricular immuno-chemotherapy in humans and to evaluate the safety of two dose levels of intraventricular rituximab as well as its pharmacokinetics in combination with intraventricular methotrexate (MTX). Secondary goals are to obtain information regarding the efficacy of this approach in the treatment of patients with recurrent CNS lymphoma, (brain parenchyma, intraocular or the leptomeningeal compartment). Methods: Thirteen patients with recurrent/refractory CD20+ CNS NHL were treated at UCSF, Dana Farber Cancer Institute and Massachusetts General Hospital on a phase I clinical trial involving twice weekly intraventricular rituximab at 10 mg and 25 mg dose levels, administered over a planned four week schedule. Rituximab is combined with MTX (12 mg) during the second intraventricular injection each week. Patients achieving partial response or better were eligible for a second month of combination intraventricular rituximab plus MTX. Results: No serious treatment-related toxicity has been detected with intraventricular rituximab/MTX at the 10 mg and 25 mg dose levels. The most common treatment-related toxicity was paresthesias (grade 1). One patient exhibited NHL progression outside of the CNS at three weeks and thus was not evaluable for CNS response, and one patient exhibited stable disease. Complete cytologic responses were detected in ten out of thirteen patients at the one-month restaging. Parenchymal responses were detected in three out of six subjects with one partial response within the corpus callosum, and two complete regressions of lesions within temporal lobe and cerebral cortex. One patient with leptomeningeal lymphoma non-responsive to intravenous rituximab and refractory to high-dose intravenous and intrathecal methotrexate, oral temozolomide and intrathecal liposomal cytarabine, obtained a sustained complete response with the intraventricular rituximab/MTX protocol and subsequently was approved for consolidative autologous stem cell transplant. Two patients have participated in extended dosing on protocol without progression for five and eight months respectively. Thus far, there is no evidence for a relationship between FcGR3A polymorphism and therapeutic resistance in a preliminary analysis (n=8 patients). The maximum tolerated dose of intraventricular rituximab with this combination was established as 25 mg. The mean maximum intraventricular rituximab concentration after intraventricular injection of rituximab was 285 microgram/ml at the 10 mg dose level (N=3) and 882 microgram/ml at the 25 mg dose level (N=10); (p<0.038). The rate of Rituximab clearance from the intraventricular compartment at two hours post injection was 30% slower when administered in combination with methotrexate compared to intraventricular rituximab monotherapy (p <0.02). Conclusions: Intraventricular rituximab/MTX appears to be safe in recurrent CNS NHL. Twelve of thirteen patients completed at least one month of therapy, without any treatment-associated serious adverse events at any of the institutions. Intraventricular administration of methotrexate may significantly attenuate rituximab clearance from the leptomeningeal compartment. There is encouraging evidence for significant activity of intraventricular immuno-chemotherapy in the treatment of drug-resistant CNS NHL, refractory or non-responsive to intravenous rituximab. These results provide strong support for further investigation of this novel therapeutic approach. NCT00221325. Supported by Leukemia and Lymphoma Society and NIH Grant CA13908301. Disclosures: Off Label Use: We will discuss the off-label use of rituximab within the leptomeningeal compartment to treat recurrent/refractory CNS lymphomas. Advani:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Phase II Study of All-Trans Retinoic Acid (ATRA), Arsenic Trioxide (ATO), with or without Gemtuzumab OzogamIcin (GO) for the Frontline Therapy of Patients with Acute Promyelocytic Leukemia (APL).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1080-1080 ◽  
Author(s):  
Farhad Ravandi ◽  
Elihu H. Estey ◽  
Jorge E. Cortes ◽  
Susan O'Brien ◽  
Sherry A. Pierce ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Gemtuzumab Ozogamicin ◽  
Off Label Use ◽  
Free Survival ◽  
Off Label ◽  
All Trans Retinoic Acid ◽  
Risk Patients ◽  
Label Use

Abstract Abstract 1080 Background: The role of arsenic trioxide (ATO) in the frontline treatment of patients with acute promyelocytic leukemia (APL) remains unclear with a number of studies reporting high and durable responses with single agent ATO. We have conducted a trial combining all-trans-retinoic acid (ATRA) with ATO with or without gemtuzumab ozogamicin (GO) in patients with previously untreated APL. Patients and methods: From July 2002 to June 2010, 104 patients with newly diagnosed APL were treated with a combination of ATRA plus ATO in two studies. The first cohort of 47 patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily beginning on day 10 of ATRA). High-risk patients (White blood cell count [WBC] > 10 × 109/L) received GO 9 mg/m2 on the first day of induction. From July 2007, the second cohort of 57 patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) concomitantly on day one of induction. They also received GO 9 mg/m2 on day 1, if high risk, and any time during induction if the WBC rose to > 30 × 109/L (and more recently if > 10 × 109/L). Monitoring for PML-RARA fusion gene using reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted after induction and throughout consolidation and follow up. The median age for the 104 patients was 46 years (range, 14–81). Their median presenting WBC was 2.7 × 109/L (0.4-131.4 × 109/L) and their median platelet count was 36 × 109/L (range, 7–261 × 109/L). Seventy three (70%) had low risk and 31 (30%) high risk disease (based only on the presentation WBC ≤ or > 10.0 × 109/L). Results: Overall, 102 patients (98%) achieved complete remission (CR) and 2 died during induction. With a median follow-up of 115 weeks (range, 4 to 397 weeks), 94 patients remain alive. The estimated 5-year survival rate was 88% and event-free survival 86%; only 5 of the patients achieving a CR (5%) have relapsed. The median overall survival, remission duration and event-free survival have not been reached (Figure). Thirty six patients have been alive and in remission for more than 3 years and 21 for more than 5 years. Two late deaths (beyond 300 weeks) occurred in CR from unrelated causes. Conclusion: The combination of ATRA and ATO (with or without GO) as initial therapy for APL is highly effective and safe; it can potentially substitute for chemotherapy containing regimens in high and low risk patients. Disclosures: Ravandi: Cephalon: Honoraria, Research Funding, Speakers Bureau. Off Label Use: Off-label use of arsenic trioxide in frontline therapy of APL; off label use of gemtuzumab ozogamicin in APL. Verstovsek:Incyte Corporation: Research Funding.

scholarly journals Off-label Use of High-Risk Cardiovascular Devices

2017 ◽  
Vol 2 (8) ◽  
pp. 832
Author(s):  
Karen E. Joynt ◽  
Daniel B. Kramer
Keyword(s):  
High Risk ◽  
Off Label Use ◽  
Cardiovascular Devices ◽  
Off Label ◽  
Label Use
Sign in / Sign up

Export Citation Format

Share Document