Advertisement

Topics

Pharmacokinetics of Asparaginase and Antibody Formation in Interfant-06

2014-08-27 03:17:31 | BioPortfolio

Summary

Asparaginase is an important drug in the treatment of childhood leukemia including in infant (<1 year). The prognosis for infants is bad.

Information about drug metabolism in neonates and infants is scarce as well as the reactions of an immature immune system to foreign proteins. The aims of this study is to describe the metabolism (pharmacokinetics) of asparaginase after administration intramuscularly and to evaluate the formation of antibodies against the drug (enzyme) during treatment in order to optimize the asparaginase treatment in infants in the future.

Description

Combination chemotherapy for acute lymphoblastic leukaemia (ALL) usually includes a bacterial L-asparaginase enzyme derived from Escherichia coli or Erwinia species. Several studies have described the pharmacokinetics in children above 1 year of age of asparaginase given intramuscularly as well as intravenously. The development of anti-asparaginase antibodies to these foreign proteins has also been described.

Chemotherapy for infant ALL also includes L-asparaginase. However, the pharmacokinetics of asparaginase and antibody formation in infants is needed to be described to optimize therapy for this group of patients who have a doubtful prognosis.

Background In general the information about drug metabolism in neonates and infants is scarce as well as the reactions of an immature immune system to foreign proteins. Several pharmacokinetic studies have been performed in children above one year of age, but no data is available about pharmacokinetics and antibody formation during treatment with any asparaginase preparation in infants.

Pharmacokinetics:

Asparaginase is used in the treatment of childhood ALL since it depletes the blood of asparagines, which can be synthesized by normal cells but not by leukemic lymphoblasts. It has been shown that serum activities above 100 IU/l ensure depletion of asparagine in serum and CNS. In many cases even values considerably lower than 100 IU/l will deplete asparagine from the serum1-5.

In the Interfant-06 protocol the doses of asparaginase are adopted from childhood ALL-protocols without scientific foundation. Infants may metabolise asparaginase differently and thus may not achieve amino acid depletion.

Antibody formation:

Asparaginase is a foreign protein for the human body, so patients may develop antibodies against it, resulting in allergic reactions (probably mediated by IgE-antibodies) or silent antibodies (IgG antibodies, blocking the effect of the enzyme). In the first case treatment most often is stopped and in the second case treatment is insufficient6-7, and thus giving the patient a poorer prognosis in both cases.

In Interfant-06 patients are treated with native E.coli asparaginase for a period followed by PEG-asparaginase later during their treatment. Studies in older children have shown that approximately 1/3 of the patients develop IgG-antibodies against native E.coli after 5-6 doses7. Other studies have shown that IgG-antibodies against native E.coli asparaginase cross-react with PEG-asparaginase, resulting in a faster clearance of the enzyme8. Allergic reactions (any grade) to native E.coli asparaginase are encountered in approximately 30 % of children11-12. There is no knowledge about the frequency of antibody formation during asparaginase therapy in infants.

Aim

The study has the purposes:

- to describe the pharmacokinetics of intramuscular native E.coli and PEG-asparaginase in children below 1 year at diagnosis

- to evaluate antibody formation during asparaginase treatment with E.coli followed by PEG-asparaginase in infants

Study Design

Observational Model: Case-Only, Time Perspective: Prospective

Conditions

Leukemia

Location

Aarhus University Hospital, Department of Pediatrics Skejby Hospital
Aarhus
Aarhus N
Denmark
8200

Status

Recruiting

Source

Aarhus University Hospital

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:17:31-0400

Clinical Trials [1385 Associated Clinical Trials listed on BioPortfolio]

Banking of Chronic Lymphocytic Leukemia Tumor Cells for Vaccine Generation

The purpose of this research study is to collect, freeze and store leukemia cells from the blood or bone marrow of patients that have advanced chronic lymphocytic leukemia (CLL) that is no...

Diagnostic Study of Patients With Acute Lymphoblastic Leukemia or Acute Promyelocytic Leukemia

RATIONALE: Determination of genetic markers for acute lymphoblastic leukemia and acute promyelocytic leukemia may help identify patients with this disease and help predict the outcome of t...

Vaccination in the Peripheral Stem Cell Transplant Setting for Acute Myelogenous Leukemia

The purpose of this study is to evaluate clinical and laboratory safety associated with the administration of GVAX leukemia vaccine and to determine the feasibility of generation of GVAX l...

Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

RATIONALE: Drugs used in chemotherapy, such as flavopiridol, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. PURP...

CAR-T Cells Therapy in Relapsed/Refractory Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a group of genetically highly heterogeneous malignant disease . The disease is the most common type of adult acute leukemia. Overall survival (OS) was less ...

PubMed Articles [1049 Associated PubMed Articles listed on BioPortfolio]

Extracellular vesicles in leukemia.

Extracellular vesicles (EV) are nano-sized membrane enclosed vehicles that are involved in cell-to-cell communication and carry cargo that is representative of the parent cell. Recent studies have hig...

Transformation from promyelocytic leukemia with t (15; 17) ( q22; q21) to acute monocytic leukemia with t (11; 17) (q23; q21) in a case.

To report on a case of therapy-related acute monocytic leukemia(t-AML) with t(11;17) (q23;q21)/MLL-AF17q after successful treatment for acute promyelocytic leukemia(APL) with t(15;17) (q22;q21)/PML-RA...

T-Lymphoblastic Leukemia/Lymphoma With Annular Skin Rash and Epidermotropism.

Leukemia cutis is uncommon in patients with acute lymphoblastic leukemia. It typically presents with dermal papules or subcutaneous nodules, with no epidermal or upper papillary dermal involvement on ...

Widespread use of measurable residual disease in acute myeloid leukemia practice.

Measurable residual disease (MRD) has prognostic importance for patients with acute myeloid leukemia (AML). How leukemia providers incorporate MRD into routine practice remains undefined.

Treating Adult Acute Lymphoblastic Leukemia in Brazil-Increased Early Mortality Using a German Multicenter Acute Lymphoblastic Leukemia-based regimen.

Acute lymphoblastic leukemia (ALL) in adults is an invariably aggressive and rare disease. Its treatment is based on the use of multidrug regimens, which have been improved since the 1970s. Few publis...

Medical and Biotech [MESH] Definitions

A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.

A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.

A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.

A chronic leukemia characterized by a large number of circulating prolymphocytes. It can arise spontaneously or as a consequence of transformation of CHRONIC LYMPHOCYTIC LEUKEMIA.

A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.

More From BioPortfolio on "Pharmacokinetics of Asparaginase and Antibody Formation in Interfant-06"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Drug Discovery
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...

Pediatrics
Pediatrics is the general medicine of childhood. Because of the developmental processes (psychological and physical) of childhood, the involvement of parents, and the social management of conditions at home and at school, pediatrics is a specialty. With ...


Searches Linking to this Trial