scholarly journals Highly Variable Pharmacokinetics of Once-Daily Intravenous Busulfan When Combined with Fludarabine in Pediatric Patients: Phase I Clinical Study for Determination of Optimal Once-Daily Busulfan Dose Using Pharmacokinetic Modeling

2012 ◽  
Vol 18 (6) ◽  
pp. 944-950 ◽  
Author(s):  
Ji Won Lee ◽  
Hyoung Jin Kang ◽  
Seung Hwan Lee ◽  
Kyung-Sang Yu ◽  
Nam Hee Kim ◽  
...  
Keyword(s):  
Clinical Study ◽  
Phase I ◽  
Pediatric Patients ◽  
Pharmacokinetic Modeling ◽  
Once Daily

Phase I and pharmacokinetic (PK) study of lenalidomide (LEN) in pediatric patients with relapsed/refractory solid tumors or myelodysplastic syndrome (MDS): A Children's Oncology Group Phase I Consortium study

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10023-10023
Author(s):  
S. L. Berg ◽  
H. Russell ◽  
M. Cairo ◽  
A. M. Ingle ◽  
P. C. Adamson ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Pediatric Patients ◽  
Phase 1 ◽  
Fixed Dose ◽  
Ischemic Event ◽  
Thromboembolic Risk ◽  
Once Daily ◽  
Antiproliferative Effects ◽  
Dose Levels

10023 Background: LEN, which has immunomodulatory, antiangiogenic, and antiproliferative effects, is indicated for the treatment of adults with MDS and multiple myeloma. We report the final results of a phase 1 and PK study of LEN in children with recurrent or refractory solid tumors (ST) or MDS. Methods: LEN was administered by mouth once daily for 21 of 28 days. Cohorts of 3 to 12 children with ST were enrolled at 15, 25, 40, 55 and 70 mg/m2/d dose levels. Children with MDS received a fixed dose of 5 mg/m2/d. PK and correlative biology studies were performed in cycle 1. Results: 49 patients (23 female), median age 16 years (range, 1–21) were enrolled and received a median of 1 cycle (range 1–11). 39/46 ST patients and 3/3 MDS patients were fully evaluable for toxicity. 0/3 patients with MDS had DLT. At 15 mg/m2/d, 1/6 ST patients developed DLT (Gr 3 hypercalcemia). At 25 mg/m2/d 1 patient had a cerebrovascular ischemic event of uncertain relationship to LEN; future subjects were screened for thromboembolic risk factors prior to enrollment. At 40 mg/m2/d 3/12 patients developed DLTs (Gr 3 hypophosphatemia/hypokalemia; Gr 4 neutropenia delaying the start of the next cycle for > 7 days; Gr 3 somnolence); at 55 mg/m2/d 1/6 patients developed DLT (Gr 3 urticaria). At 70 mg/m2/d 0/6 patients had DLT. No further dose escalation was attempted. No objective responses were observed. LEN enhanced IL-2 and IL-15 concentrations; NK expansion and activation; and NK and LAK cytotoxicity (Ayello, ASH, 2008). The median apparent LEN clearance and half-life were 135 ± 45 ml/min/m2 and 2.3 ± 1.1 hr. Conclusions: LEN is well tolerated at doses up to 70 mg/m2/d x 21d of 28 days in children with recurrent or refractory ST. Enhancement of immune function is significant. PK parameters in children are similar to those in adults. No significant financial relationships to disclose.

Phase I and Pharmacokinetic Study of Topotecan Administered Orally Once Daily for 5 Days for 2 Consecutive Weeks to Pediatric Patients With Refractory Solid Tumors

2004 ◽  
Vol 22 (5) ◽  
pp. 829-837 ◽  
Author(s):  
Najat C. Daw ◽  
Victor M. Santana ◽  
Lisa C. Iacono ◽  
Wayne L. Furman ◽  
Dana R. Hawkins ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Pediatric Patients ◽  
Radiation Recall ◽  
Time Curve ◽  
Once Daily ◽  
Injectable Formulation ◽  
P 16 ◽  
Grade 3 ◽  
Oral Topotecan

Purpose We conducted a phase I trial of the injectable formulation of topotecan given orally once daily for 5 days for 2 consecutive weeks (qd × 5 × 2) in pediatric patients with refractory solid tumors. Patients and Methods Cohorts of two to six patients received oral topotecan at 0.8, 1.1, 1.4, 1.8, and 2.3 mg/m2/d every 28 days for a maximum of six courses. Twenty patients (median age, 10.6 years) received a total of 51 courses. Eight patients received topotecan capsules during course 2 only. Results Dose-limiting toxicity occurred at 2.3 mg/m2/d and consisted of prolonged grade 4 neutropenia (n = 2), grade 3 stomatitis as a result of radiation recall (n = 1), grade 3 hemorrhage (epistaxis) in the presence of grade 4 thrombocytopenia (n = 1), and grade 3 diarrhea in the presence of Clostridium difficile infection (n = 1). Dose-limiting, prolonged grade 4 neutropenia and thrombocytopenia occurred in one patient at 1.4 mg/m2/d. Infrequent toxicities were mild nausea, vomiting, elevated liver ALT or AST, and rash. The maximum-tolerated dosage was 1.8 mg/m2/d; the mean (± standard deviation) area under the plasma concentration-time curve for topotecan lactone at this dosage was 20.9 ± 8.4 ng/mL · h. The population mean (± standard error) oral bioavailability of the injectable formulation was 0.27 ± 0.03; that of capsules was 0.36 ± 0.06 (P = .16). Disease stabilized in nine of 19 assessable patients for 1.5 to 6 months. Conclusion Oral topotecan (1.8 mg/m2/d) on a qd × 5 × 2 schedule is well tolerated and warrants additional testing in pediatric patients.

scholarly journals Phase I clinical study of oral olaparib in pediatric patients with refractory solid tumors: study protocol

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Masatoshi Takagi ◽  
Chitose Ogawa ◽  
Yuki Aoki-Nogami ◽  
Tomoko Iehara ◽  
Eri Ishibashi ◽  
...  
Keyword(s):  
Clinical Study ◽  
Phase I ◽  
Solid Tumors ◽  
Study Protocol ◽  
Pediatric Patients

The Frequency of HIV-1 Infection in Iranian Children and Determination of the Transmitted Drug Resistance in Treatment-Naïve Children

2020 ◽  
Vol 17 (6) ◽  
pp. 397-407
Author(s):  
Maryam Jarchi ◽  
Farah Bokharaei-Salim ◽  
Maryam Esghaei ◽  
Seyed Jalal Kiani ◽  
Fatemeh Jahanbakhsh ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Pediatric Patients ◽  
Phylogenetic Analyses ◽  
Rna Extraction ◽  
Transmitted Drug Resistance ◽  
The Arts ◽  
Treatment Naïve ◽  
Iranian Children ◽  
Hiv 1

Background: The advent of resistance-associated mutations in HIV-1 is a barrier to the success of the ARTs. Objective: In this study, the abundance of HIV-1 infection in Iranian children, and also detection of the TDR in naïve HIV-1 infected pediatric (under 12 years old) were evaluated. Materials: From June 2014 to January 2019, a total of 544 consecutive treatment-naïve HIV-1- infected individuals enrolled in this study. After RNA extraction, amplification, and sequencing of the HIV-1 pol gene, the DRM and phylogenetic analysis were successfully performed on the plasma specimens of the ART-naïve HIV-1-infected-children under 12 years old. The DRMs were recognized using the Stanford HIV Drug Resistance Database. Results: Out of the 544 evaluated treatment-naïve HIV-1-infected individuals, 15 (2.8%) cases were children under 12 years old. The phylogenetic analyses of the amplified region of pol gene indicated that all of the 15 HIV-1-infected pediatric patients were infected by CRF35_AD, and a total of 13.3% (2/15) of these children were infected with HIV-1 variants with SDRMs (one child harbored two related SDRMs [D67N, V179F], and another child had three related SDRMs [M184V, T215F, and K103N]), according to the last algorithm of the WHO. No PIs-related SDRMs were observed in HIV-1-infected children. Conclusion: The current study demonstrated that a total of 13.3% of treatment-naïve HIV-1-infected Iranian pediatrics (under 12 years old) were infected with HIV-1 variants with SDRMs. Therefore, it seems that screening to recognize resistance-associated mutations before the initiation of ARTs among Iranian children is essential for favorable medication efficacy and dependable prognosis.

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