A single-center, open-label clinical study to evaluate pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte stimulating factor in pediatric patients with acute lymphoblastic leukemia.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e22501-e22501
Author(s):  
Wenyu Yang ◽  
Tianfeng Liu ◽  
Xiaojuan Chen ◽  
Ye Guo ◽  
Ting Li ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Serum Concentration ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Open Label ◽  
Significant Difference ◽  
Stimulating Factor

e22501 Background: The aims of the study were to investigate the pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony stimulating factor(PEG-rhG-CSF) in pediatric patients with acute lymphoblastic leukemia(ALL), and compare the efficacy and safety of PEG-rhG-CSF (brand name:jinyouli) and rhG-CSF. Methods: Pediatric patients with newly diagnosed ALL who planned to use CAM (cyclophosphamide, cytarabine, 6-mercaptopurine) for chemotherapy were assigned to PEG-rhG-CSF group or rhG-CSF group. In the PEG-rhG-CSF group, PEG-rhG-CSF (100ug/kg) was injected subcutaneously once 48 hours after chemotherapy. In the rhG-CSF group, rhG-CSF (150ug/d) was injected subcutaneously daily from 48 hours after chemotherapy until the absolute neutrophil count (ANC) was≥1.0×109/L. The serum concentration of PEG-rhG-CSF was detected by enzyme-linked immunosorbent assay (ELISA). Safety and efficacy of the two groups were evaluated. Results: Between November 2015 to April 2016, 17 pediatric patients were assigned to PEG-rhG-CSF(n = 9) or rhG-CSF(n = 8) groups. The main pharmacokinetic parameters (mean±SD) of PEG-rhG-CSF group were as follows: Cmax was 353.50±136.3 ng/ml, Tmax was 44.00±20.8 h, t1/2 was 14.58± 2.2h. The PEG-rhG-CSF serum concentration and ANC curve were consistent with the mechanism of neutrophil mediated clearance. The average value of ANC nadir in PEG-rhG-CSF group was 0.18 (±0.32)×109/L, and the rhG-CSF group was 0.08 (±0.09)×109/L, there was no significant difference between the two groups ( P = 0.469). Compared with rhG-CSF, the average time of ANC recovery in PEG-rhG-CSF group was earlier (18.33±2.18 vs. 21.50±2.33, P = 0.021). There were no significant differences in the incidence of FN and infection, the duration of grade Ⅳ neutropenia and hospitalization, and the safety of the two groups. Conclusions: PEG-rhG-CSF had favorable efficacy in pediatric patients with ALL receiving chemotherapy, and there was no serious adverse event. Compared with rhG-CSF, PEG-rhG-CSF needed only once in each chemotherapy cycle, which is more suitable for pediatric patients. Clinical trial information: NCT02953730.

Phase II Study of Clofarabine in Pediatric Patients With Refractory or Relapsed Acute Lymphoblastic Leukemia

2006 ◽  
Vol 24 (12) ◽  
pp. 1917-1923 ◽  
Author(s):  
Sima Jeha ◽  
Paul S. Gaynon ◽  
Bassem I. Razzouk ◽  
Janet Franklin ◽  
Richard Kadota ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Phase Ii ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Median Number ◽  
Open Label ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Heavily Pretreated

Purpose To evaluate the efficacy and safety of clofarabine, a novel deoxyadenosine analog, in pediatric patients with refractory or relapsed acute lymphoblastic leukemia (ALL). Patients and Methods In a phase II, open-label, multicenter study, 61 pediatric patients with refractory or relapsed ALL received clofarabine 52 mg/m2 intravenously over 2 hours daily for 5 days, every 2 to 6 weeks. The median age was 12 years (range, 1 to 20 years), and the median number of prior regimens was three (range, two to six regimens). Results The response rate was 30%, consisting of seven complete remissions (CR), five CRs without platelet recovery (CRp), and six partial remissions. Remissions were durable enough to allow patients to proceed to hematopoietic stem-cell transplantation (HSCT) after clofarabine. Median CR duration in patients who did not receive HSCT was 6 weeks, with four patients maintaining CR or CRp for 8 weeks or more (8+, 12, 37+, and 48 weeks) on clofarabine therapy alone. The most common adverse events of grade ≥ 3 were febrile neutropenia, anorexia, hypotension, and nausea. Conclusion Clofarabine is active as a single agent in pediatric patients with multiple relapsed or refractory ALL. The toxicity profile is as expected in this heavily pretreated patient population. Studies exploring rational combinations of clofarabine with other agents are ongoing in an effort to maximize clinical benefit.

Pharmacokinetics and Pharmacodynamics of Oral Methotrexate and Mercaptopurine in Children With Lower Risk Acute Lymphoblastic Leukemia: A Joint Children’s Cancer Group and Pediatric Oncology Branch Study

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3569-3577 ◽  
Author(s):  
Frank M. Balis ◽  
John S. Holcenberg ◽  
David G. Poplack ◽  
Jeffrey Ge ◽  
Harland N. Sather ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Cox Regression Analysis ◽  
Oral Methotrexate ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Thioguanine Nucleotide

Abstract We prospectively assessed the pharmacokinetics of methotrexate, mercaptopurine, and erythrocyte thioguanine nucleotide levels in a homogenous population of children with lower risk acute lymphoblastic leukemia and correlated pharmacokinetic parameters with disease outcome. The maintenance therapy regimen included daily oral mercaptopurine (75 mg/m2) and weekly oral methotrexate (20 mg/m2). One hundred ninety-one methotrexate doses and 190 mercaptopurine doses were monitored in 89 patients. Plasma drug concentrations of both agents were highly variable. The area under the plasma concentration-time curve (AUC) of methotrexate ranged from 0.63 to 12 μmol•h/L, and the AUC of mercaptopurine ranged from 0.11 to 8 μmol•h/L. Drug dose, patient age, and duration of therapy did not account for the variability. Methotrexate AUC was significantly higher in girls than boys (P = .007). There was considerable intrapatient variability for both agents. Erythrocyte thioguanine nucleotide levels were also highly variable (range, 0 to 10 pmol/g Hgb) and did not correlate with mercaptopurine dose or AUC. A Cox regression analysis showed that mercaptopurine AUC was a marginally significant (P = .043) predictor of outcome, but a direct comparison of mercaptopurine AUC in the remission and relapsed patient groups failed to show a significant difference. Methotrexate and mercaptopurine plasma concentrations and erythrocyte thioguanine nucleotide levels were highly variable, but measurement of these pharmacokinetic parameters at the start of maintenance will not distinguish patients who are more likely to relapse.

Pharmacokinetics and pharmacodynamics of asparaginases in antibody-negative pediatric patients with higher risk acute lymphoblastic leukemia (ALL): A report from CCG-1961

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9027-9027
Author(s):  
F. J. Arce ◽  
N. Seibel ◽  
P. S. Gaynon ◽  
P. N. Tiwari ◽  
I. A. Avramis ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Amino Acid ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Early Response ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Kaplan Meier ◽  
Elimination Half ◽  
Amino Acid Levels ◽  
Increased Activity

9027 Background: Asparaginase (ASNase) induces apoptosis in ALL lymphoblasts by depleting cells of extracellular asparagine (ASN) and possibly glutamine (GLN). On CCG-1961 [Seibel NL et al. Blood 2003; 102(11): 224a (abstract #787)], all patients (pts) received 9 doses of native E.coli-ASNase in induction (IND). Pts with rapid early response (marrow blasts < 25% on Day 7, RER) were randomized to standard intensity therapy and received native ASNase thereafter or to stronger intensity therapy and received PEG-ASNase post induction. All pts with slow early response (marrow blasts ≥ 25% on Day 7, SER) received PEG-ASNase after induction. Pts with clinical allergy to E.coli-ASNase were switched to Erwinase. Methods: Anti-ASNase Antibody (Ab) titers were assayed at the end of IND, prior to Delayed Intensification #1 and prior to starting Maintenance. Amino acid levels were measured in 430 sera from 187 patients with measurable ASNase activity. Results: Population pharmacokinetics (PK) and pharmacodynamics (PD) of the ASNase formulations demonstrated half-lives of native ASNase (6000 IU/m2): 30 hours, PEG-ASNase (2500 IU/m2): 156 hours, and Erwinase (6000 IU/m2): 18 hours. Subsequent exposures to either formulation resulted in increased activity with moderate prolongation of the elimination half-lives. One-hundred forty-two sera from 70 patients with ASNase activity between 0.03 and 1.11 IU/ml, had a mean ± SDEV ASNase activity, ASN levels, and GLN levels of 0.21 ± 0.23 IU/ml, 14.6 ± 17.7 μM, and 300.4 ± 233.8 μM, respectively; with median values of 0.11 IU/ml (range: 0.03–1.114 IU/ml), 4.7 μM (range: 0.38 - 81.34 μΜ), and 270.2 μM (range: 5.3 - 1189.1 μM), respectively. TTEST analyses linked higher ASNase activity with lower ASN levels and greater % ASN deamination. Higher ASNase activity did not assure greater GLN depletion. Conclusions: A sigmoid relationship between ASNase levels and % ASN deamination showed that activity of 0.41 ± 0.24 IU/ml (mean ± SDEV) provided 93% ± 13% ASN deamination. Therefore, >90% ASN deamination required ASNase >0.4 IU/ml. Kaplan-Meier analyses are pending. [Table: see text]

Safety and Immunogenicity of High Dose Trivalent Inactivated Influenza Vaccine in Pediatric Patients with Acute Lymphoblastic Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3531-3531
Author(s):  
Meghann Pine McManus ◽  
Haydar Frangoul ◽  
Jonathan McCullers ◽  
Wenli Wang ◽  
Steve Ampath ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Lymphoblastic Leukemia ◽  
Influenza Vaccine ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Vaccine Antigen ◽  
High Dose ◽  
Children With Cancer ◽  
Significant Difference

Abstract Abstract 3531 Background: Influenza is an important cause of morbidity and mortality worldwide. Most deaths outside the elderly population are seen in other high risk groups, such as immunocompromised individuals. Compared to the general population, children with cancer have a higher frequency of influenza infections, have symptoms lasting twice as long and are more likely to require hospitalization, all of which may lead to delays in their chemotherapy. It is recommended that children with cancer receive a yearly trivalent influenza vaccine (TIV) and studies show that children with acute lymphoblastic leukemia (ALL) do mount an immune response to the TIV, although they often have lower titers and seroresponse rates compared to healthy controls. Recently, a high dose (HD) TIV was found to provide a statistically significant increase in the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized that the HD TIV would be well tolerated and more immunogenic compared to the SD TIV in pediatric patients with ALL. Methods: This was a randomized, double-blind, phase I safety and immunogenicity trial comparing HD to SD TIV in children with ALL aged 3–17 years, at least one month into chemotherapy and in 1stcomplete remission. Subjects were randomized 2:1 to receive either 0.5mL of HD (60ug per antigen) or SD (15ug per antigen) 2010–11 or 2011–12 TIV. Local and systemic reactions were collected for 7 days after each vaccination. HAI titers to influenza virus antigens as well as complete blood count, quantitative CD4, CD8, CD19 and serum IgG levels were measured before and 28–35 days after vaccination. In year 1, no blood was drawn before dose 2 if a second dose was required. Results: 50 subjects were enrolled (20 in year 1, 30 in year 2). Mean age was 8.25 years (range 4.7 – 12.3 years) and 62% were male. The majority of patients (78%) were in the maintenance phase of therapy. 34 subjects received the HD TIV and 16 subjects received the SD TIV (mean age 7.8 vs. 9.3 years), with 11 subjects receiving 2 doses (9 in HD and 2 in SD groups). The only significant difference noted between the HD and SD TIV group was mean total CD19 count (29 vs. 56, p=0.027). There were no significant differences reported in local or systemic symptoms, except fatigue/malaise and headaches were reported more frequently in the SD TIV group (p=0.008 and p=0.03, respectively). No severe adverse events were attributed to vaccination. The immune response measured by a ≥ 4-fold rise in titers for each vaccine antigen were similar in both the HD and SD TIV groups after 1 or 2 vaccines, respectively (A/California: p=0.12, p=0.46; A/Perth: p=0.35, p=0.34; B/Brisbane: p=0.42, p=0.89). Please see refer to tables 1 and 2 for further immunogenicity results. Conclusion: No differences were noted between the HD and SD TIV groups for solicited systemic and local reactions. The immune response appeared similar in both vaccine groups. A phase 3 trial is planned to determine the immunogenicity of HD versus SD TIV in the pediatric ALL population. Disclosures: No relevant conflicts of interest to declare.

Pharmacokinetics and Pharmacodynamics of Oral Methotrexate and Mercaptopurine in Children With Lower Risk Acute Lymphoblastic Leukemia: A Joint Children’s Cancer Group and Pediatric Oncology Branch Study

Blood ◽  
1998 ◽  
Vol 92 (10) ◽  
pp. 3569-3577 ◽  
Author(s):  
Frank M. Balis ◽  
John S. Holcenberg ◽  
David G. Poplack ◽  
Jeffrey Ge ◽  
Harland N. Sather ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lower Risk ◽  
Lymphoblastic Leukemia ◽  
Plasma Concentrations ◽  
Pharmacokinetic Parameters ◽  
Cox Regression Analysis ◽  
Oral Methotrexate ◽  
Drug Concentrations ◽  
Significant Difference ◽  
Thioguanine Nucleotide

We prospectively assessed the pharmacokinetics of methotrexate, mercaptopurine, and erythrocyte thioguanine nucleotide levels in a homogenous population of children with lower risk acute lymphoblastic leukemia and correlated pharmacokinetic parameters with disease outcome. The maintenance therapy regimen included daily oral mercaptopurine (75 mg/m2) and weekly oral methotrexate (20 mg/m2). One hundred ninety-one methotrexate doses and 190 mercaptopurine doses were monitored in 89 patients. Plasma drug concentrations of both agents were highly variable. The area under the plasma concentration-time curve (AUC) of methotrexate ranged from 0.63 to 12 μmol•h/L, and the AUC of mercaptopurine ranged from 0.11 to 8 μmol•h/L. Drug dose, patient age, and duration of therapy did not account for the variability. Methotrexate AUC was significantly higher in girls than boys (P = .007). There was considerable intrapatient variability for both agents. Erythrocyte thioguanine nucleotide levels were also highly variable (range, 0 to 10 pmol/g Hgb) and did not correlate with mercaptopurine dose or AUC. A Cox regression analysis showed that mercaptopurine AUC was a marginally significant (P = .043) predictor of outcome, but a direct comparison of mercaptopurine AUC in the remission and relapsed patient groups failed to show a significant difference. Methotrexate and mercaptopurine plasma concentrations and erythrocyte thioguanine nucleotide levels were highly variable, but measurement of these pharmacokinetic parameters at the start of maintenance will not distinguish patients who are more likely to relapse.

Gut bacterial gene changes following pegaspargase treatment in pediatric patients with acute lymphoblastic leukemia

2021 ◽  
pp. 1-12
Author(s):  
Katherine A. Dunn ◽  
Zara Forbrigger ◽  
Jessica Connors ◽  
Mushfiqur Rahman ◽  
Alejandro Cohen ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Bacterial Gene

Screening for asymptomatic diabetes and metabolic comorbidities in pediatric patients during therapy for acute lymphoblastic leukemia

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Valerie Larouche ◽  
Caroline Bellavance ◽  
Pauline Tibout ◽  
Sebastien Bergeron ◽  
David Simonyan ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Fasting Blood Glucose ◽  
Metabolic Disturbances ◽  
Metabolic Complications ◽  
Glucose Levels ◽  
Oncology Unit ◽  
Hba1c Levels

Abstract Objectives Chronic metabolic disturbances related to cancer treatment are well reported among survivors of pediatric acute lymphoblastic leukemia (ALL). However, few studies have investigated the incidence of these complications during the phase of chemotherapy. We evaluated the incidence of acute metabolic complications occurring during therapy in our cohort of patients diagnosed with ALL. Methods A prospective study involving 50 ALL pediatric patients diagnosed and treated between 2012 and 2016 in our oncology unit. We collected weight, blood pressure, fasting plasma glucose and hemoglobin A1C (HBA1c) levels during the two years of therapy. Results Obesity and overweight occurred in 43 and 25%, respectively among patients and have been reached at 12 months of chemotherapy. About 26% of the patients developed high blood pressure and 14% experienced hyperglycemias without meeting diabetes criteria. There was a significant decrease of HBA1c levels between the beginning and the end of therapy (p<0.0001). Conclusions Increase of body mass index in our ALL pediatric patients occurred during the first months of therapy and plateaued after a year of treatment. We should target this population for early obesity prevention. HbA1c levels measured during therapy did not reveal diabetes criteria. Hence, fasting blood glucose levels are sufficient to monitor ALL pediatric patients’ glycemia.

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