Clinical trial · Interventional
Vorinostat in Children
Phase I/II Intra-patient Dose Escalation Study of Vorinostat in Children With Relapsed Solid Tumor, Lymphoma or Leukemia
NCT01422499CI-TRIAL-00032472completedPhase 1 / Phase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The aim of this study is to define a dose recommendation of vorinostat in pediatric oncology, to determine pharmacokinetics of vorinostat in children, determine response rates, safety and feasibility.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Children With Relapsed Solid Tumor, Lymphoma or Leukemia | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| zolinza/vorinostat | Drug | Vorinostat | ALIAS |
Design
Arms and outcomes
Arms (0)
[]Primary outcomes (1)
- measure
- To determine a safe dose recommended (SDR) for the routine application of oral vorinostat (involving dose escalation) in children and adolescents (3-18 years) with relapsed/refractory solid tumor, lymphoma or leukemia.
- timeFrame
- After finding the individual MTD this dose will be applied for 3 months. Patients without progression at first response evaluation will continue treatment for a maximum of 9 months.
- description
- A SDR is defined as the highest dose with no ≥ grade 3 toxicity according to CTC criteria (Dose Limiting Toxicity) in no more than 1/50 patient in this study. Dose Limiting Toxicity (DLT) is defined as any grade 3 or 4 toxicity according the CTCAE version 4.0 and judged by the investigator as definitely, probably or possibly related to the study drug. However, all DLTs will be subject to a second assessment by the Coordinating Investigator or a designated person.
Secondary outcomes (5)
- measure
- pharmacokinetics
- timeFrame
- d 8, when maximum tolerated dose (MTD) ist reached and after 3 months treatment at MTD
- description
- Quantification of vorinostat concentration by mass spectrometry and enzymatically (AUC, Cmax, Cmin, tmax, Clearance, and t1/2). The pharmacokinetic study will investigate the correlation between dose administered, plasma concentration, CSF concentrations, intracellular inhibition of HDAC activity and glucuronosyltransferase polymorphisms as well as observed treatment responses and toxicities. Additionally:Intracellular HDAC activity in leukocytes using a fluorescence based enzymatic assay
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 3 Years
- Maximum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Children and adolescents (3-18 years) with relapsed or therapy-refractory solid tumor, lymphoma or leukemia following standard first-line or relapse protocols in pediatric oncology * Diagnosis confirmed by one of the Pathological, Radiological or Study Reference Centers recognized by the GPOH * No other simultaneous anti-neoplastic treatment or radiation during the study and 1 months before enrolment * Sufficient general condition (Lansky Score \>50%) * Life expectancy \> 3 months * Liver enzymes (ALT or AST) \< 5x upper limit of normal reference value, bilirubin and creatinine \< 3x upper limit of normal reference value * Solid tumors: leukocytes \> 2000/µl, thrombocytes \> 50.000/µl and adequate bone marrow function to permit evaluations of hematopoietic toxicity * No CTC grade 3 or 4 toxicity from previous treatments * Normal ECG * Written informed consent of the legal representatives and the patient if the patient is able to understand the study situation and to give consent (must be available before enrolment in the trial) * Women with childbearing potential agree to use adequate contraception or to abstain from heterosexual activity throughout the study, starting with Visit 1. * Sexually active male patient agrees to use an adequate method of contraception for the duration of the study * Solid tumors: measurable disease activity according to RECIST criteria Exclusion Criteria: * History of deep vein thrombosis or pulmonary embolism * Pregnancy and lactation * Patient with concomitant treatments and/or anti-neoplastic treatment such as chemotherapy, immune therapy, and differentiation therapy, other targeted therapy, radiation. The use of valproic acid as prior antiepileptic therapy is allowed with a 30-day washout period. * Prior exposure to Histone Deacetylase Inhibitors * Known active HBV, HCV or HIV infection * Patient with concomitant treatments such as amber \[Hypericum perforatum\], plant extracts, vitamins, and other anti-oxidative compounds * Participation in other clinical trials or observation period of competing trials, respectively * Patient is unable to swallow vorinostat suspension or capsules * Patient on coumarin-derivative anticoagulants * Any other medication which could accentuate known dose-dependent adverse effects of the study drug, for instance bone marrow depression or QT-prolongation
References
Publications (2)
- DERIVEDvan Tilburg CM, Milde T, Witt R, Ecker J, Hielscher T, Seitz A, Schenk JP, Buhl JL, Riehl D, Fruhwald MC, Pekrun A, Rossig C, Wieland R, Flotho C, Kordes U, Gruhn B, Simon T, Linderkamp C, Sahm F, Taylor L, Freitag A, Burhenne J, Foerster KI, Meid AD, Pfister SM, Karapanagiotou-Schenkel I, Witt O. Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia. Clin Epigenetics. 2019 Dec 10;11(1):188. doi: 10.1186/s13148-019-0775-1. PMID 31823832
- DERIVEDWitt O, Milde T, Deubzer HE, Oehme I, Witt R, Kulozik A, Eisenmenger A, Abel U, Karapanagiotou-Schenkel I. Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma or leukemia. Klin Padiatr. 2012 Oct;224(6):398-403. doi: 10.1055/s-0032-1323692. Epub 2012 Aug 22. PMID 22915450