Symptoms and General Pathology

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Rare Diseases

Syndrome

Leukemia

Anemia

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Myelodysplastic Syndromes

Hematologic Diseases

Bone Marrow Diseases

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Anti-Infective Agents

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All Drugs and Chemicals

Cyclosporine

Cyclosporins

Immunosuppressive Agents

Antilymphocyte Serum

Enzyme Inhibitors

Immunologic Factors

Clotrimazole

Miconazole

Antifungal Agents

Calcineurin Inhibitors

Antithymocyte globulin

Approximately 40% of the patients with myelodysplastic syndrome (MDS) die as a consequence of their cytopenia. As in aplastic anemia, the cytopenia of MDS may be partly due to cytotoxic T cell activity. Immunosuppressive therapy may therefore reverse the cytopenia. In a phase II pilot study of anti-thymocyte globin (ATG) to treat myelodysplastic syndrome (MDS); 41% of patients (61% of patients with refractory anemia) have responded in terms of transfusion independence. Recently, Jonasova et al \[32\] reported a 82% substantial hematological response rate in 18 patients with MDS of the refractory anemia (RA) subtype treated with cyclosporine alone. Just over 50% of the patients in this series had MDS of the hypocellular type. Cyclosporine alone if indeed efficacious would be a powerful therapeutic option that could be readily used by hematologists in the community to treat patients with MDS. This efficacy needs to be proven in a larger study which includes patients with the other subtypes of MDS and more patients with the non-hypocellular forms of MDS (which constitute approximately 70% of the cases in the community). As MDS is a heterogeneous group of disorders, a randomized comparison with the other immunomodulating intervention of proven benefit, ATG, is appropriate. In this randomized study patients with MDS will receive either ATG alone or cyclosporine alone.

Approximately 40% of the patients with myelodysplastic syndrome (MDS) die as a consequence of their cytopenia. As in aplastic anemia, the cytopenia of MDS may be partly due to cytotoxic T cell activity. Immunosuppressive therapy may therefore reverse the cytopenia. In a phase II pilot study of anti-thymocyte globulin (ATG) to treat myelodysplastic syndrome (MDS); 41% of patients (61% of patients with refractory anemia) have responded in terms of transfusion independence. Recently, Jonasova et al \[32\] reported a 82% substantial hematological response rate in 18 patients with MDS of the refractory anemia (RA) subtype treated with cyclosporine alone. Just over 50% of the patients in this series had MDS of the hypocellular type. Cyclosporine alone if indeed efficacious would be a powerful therapeutic option that could be readily used by hematologists in the community to treat patients with MDS. This efficacy needs to be proven in a larger study which includes patients with the other subtypes of MDS and more patients with the non-hypocellular forms of MDS (which constitute approximately 70% of the cases in the community). As MDS is a heterogeneous group of disorders, a randomized comparison with the other immunomodulating intervention of proven benefit, ATG, is appropriate. In this randomized study patients with MDS will receive either ATG alone or cyclosporine alone.

A Randomized Trial of Antithymocyte Globulin Versus Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome

National Institutes of Health Clinical Center (CC)

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Infections

Skin and Connective Tissue Diseases

Kidney Diseases

Communicable Diseases

Exanthema

Urologic Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Male Urogenital Diseases

Antineoplastic Agents

Everolimus

Itraconazole

Mycophenolic Acid

Tacrolimus

Sirolimus

Voriconazole

Fluconazole

Hydroxyitraconazole

Posaconazole

Patients treated for their regular patient care with mycophenolic acid.

Patients treated for their regular patient care with cyclosporin.

Patients treated for their regular patient care with tacrolimus.

Patients treated for their regular patient care with sirolimus.

Patients treated for their regular patient care with everolimus.

Patients treated for their regular patient care with voriconazole.

Patients treated for their regular patient care with posaconazole.

Patients treated for their regular patient care with itraconazole.

Patients treated for their regular patient care with fluconazole.

The association between conventional venous sampling and finger prick dried blood spot (DBS) will be associated by drawing blood in both ways.

blood drawing

Roger Bruggemann, PharmD PhD

This is a clincial validation study of a dried blood spot (DBS) method for the analysis of immunosuppressive and antifungal agents currently subject of therapeutic drug monitoring (TDM) in a pediatric population.

The primary goal is to clinically validate a finger prick DBS method compared to conventional venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the pediatric population. Secondairy goals include feasibility of the finger prick DBS method in the target population, to design an inventory of costs that will be incurred in future health-economic analyses and to construct a population PK model based on the available data collected for the primariy goal.

Therapeutic drug monitoring (TDM) offers the possibility to individualize and improve a patient's pharmacological treatment, based on the measurement of drug concentrations in biological samples. Conventionally, TDM is performed with blood or plasma obtained by venous blood sampling. This method is associated with several challenges such as i) the need for the patient to travel to the hospital or health center; ii) special conditions for sample transport to guarantee stability of the analyte and to decrease the biohazard risk; iii) sampling times not always representing the preferable peak or trough concentrations; iv) the method being invasive and v) delay of the outcome of the analyses with regard to the outpatient visit.

The Dried Blood Spot (DBS) may offer a solution for all these challenges. DBS is thought to offer benefits over plasma venous sampling for TDM. The main purpose of the PROTECT (Personalized treatment of immunosuppressive and antifungal drugs through continuous home based monitoring with Dried Blood Spot sampling techniques in pediatric patients) study is to improve therapeutic management and patient participation in pediatric patients treated with antifungal and immunosuppressive agents. PROTECT is mainly financed by a ZonMW grant 'Goed Gebruik Geneesmiddelen'.

Four patient organizations are actively involved in the PROTECT study.

Objective of the study:

Primairy To clinically validate a finger prick DBS method compared to conventional venous sampling for the analysis of 5 immunosuppressive and 4 azole antifungal drugs in the pediatric population. Secondairy

* Feasibility of the novel finger prick DBS method in the pediatric population will be assessed. This includes scoring of relevant characteristics (attributes) of blood drawing methods for TDM, evaluation of the experience and attitude of both patients and parents regarding finger prick DBS sampling and evaluation of the understanding of the written instructions provided for performing the finger prick at home. The data obtained in this validation study will be used for the implementation of the DBS in therapeutic drug monitoring (TDM) being a less invasive procedure, and as a base for a discrete choice-experiment as part of the HTA.
* To design an inventory of types of costs that will be incurred in the process of DBS-based and conventional TDM as a preparation step for later health economic analysis.
* Data from this study will be used to construct a population pharmacokinetic model to optimize dosing and design new guidelines.

This is an observational mono-centre study in which DBS sampling is compared with conventional sampling for TDM in a steady state situation.

Clearly, information on feasibility of DBS sampling in children and on costs relevant to DBS sampling in children can only be obtained through actual sampling in children.

Plasma without DNA, blood with DNA and dried blood spot (with DNA)

Clinical Validation of a Dried Blood Spot Method for Analysis of Immunosuppressives and Antifungals in Pediatrics

Clinical Validation of a Dried Blood Spot (DBS) Method for the Analysis of Immunosuppressive and Antifungal Drugs in Pediatric Patients (Part of the PROTECT Study).

The outcome measure is a composite of several blood concentrations, obtained by three individual blood drawing moments per patient. The related endpoint is the evaluation of the association between the concentration obtained by venous sampling and the concentration obtained by means of DBS sampling. The predictive performance of the DBS method as a measure for the venous concentration will be evaluated.

The related endpoint is the response to a questionnaire. Results will be used to prepare implementation of the novel method for home-based monitoring as well as to prepare a HTA analysis.

Costs of blood drawing methods will be collected.The cost types will function as a basis for future HTA analysis of this novel sampling method compared to conventional venous sampling.

Blood concentrations will be used to calculate the area under the concentration time curve (AUC). The outcome measure will be a composite of population estimates of the pharmacokinetic parameters AUC, maximal concentration (Cmax), time to maximal concentration (Tmax), clearance (CL), volume of distribution (Vd) and elimination half-life (t1/2).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Randomized Trial of Antithymocyte Globulin Versus Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome	NCT00001839	Hematologic Dis... Myelodysplastic...	Antithymocyte g... Cyclosporine	-	National Institutes of Health Clinical Center (CC)
A Randomized Trial of Antithymocyte Globulin Versus Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome	NCT00001839	Hematologic Dis... Myelodysplastic...	Antithymocyte g... Cyclosporine	-	National Institutes of Health Clinical Center (CC)
Clinical Validation of a Dried Blood Spot Method for Analysis of Immunosuppressives and Antifungals in Pediatrics	NCT02329808	Hematologic Dis... Oncology Proble... Kidney Diseases Transplantation...	blood drawing	2 Years - 18 Years	Radboud University Medical Center
A Randomized Trial of Antithymocyte Globulin Versus Cyclosporine to Treat the Cytopenia of Myelodysplastic Syndrome	NCT00001839	Hematologic Dis... Myelodysplastic...	Antithymocyte g... Cyclosporine	-	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for immunosuppressive