A Phase I Study of 17-AAG in Relapsed/Refractory Pediatric Patients With Solid Tumors or Leukemia
tanespimycin
Maladies Hématologiques+9
+ Maladies hématologiques et lymphatiques
+ Maladies du Système Immunitaire
Étude thérapeutique
Résumé
Date de début de l'étude : 1 mars 2004
Date à laquelle le premier participant a commencé l'étude.PRIMARY OBJECTIVES: I. To estimate the maximum tolerated dose (MTD) and recommended phase II dose of 17-AAG administered as a 60 or 120-minute intravenous infusion on days 1, 4, 8, and 11, of a 21-day course, to children with refractory solid tumors or relapsed leukemia. II. To define and describe the toxicities of 17-AAG administered on this schedule. III. To characterize the pharmacokinetics of 17-AAG in children with refractory cancer. SECONDARY OBJECTIVES: I. To preliminarily define the antitumor activity of 17-AAG within the confines of a phase I study. II. To assess the biologic activity of 17-AAG. III. To examine the role of CYP3A5 polymorphisms in the pharmacologic and clinical phenotypes observed following administration of 17-AAG to children, within the confines of a phase 1 study. OUTLINE: This is a dose-escalation, multicenter study. Patients with solid tumors receive 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) IV over 60-120 minutes on days 1, 4, 8, and 11. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-AAG until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 6 additional patients with leukemia receive 17-AAG at the MTD as above. If these 6 patients tolerate this regimen, another 6 leukemia patients receive 17-AAG IV over 60 minutes on days 1, 4, 8, 11, 15, and 18. Treatment repeats every 28 days for 17 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 30 days.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.36 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.De 1 à 21 ans
Tranche d'âge des participants éligibles à participer.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
Inclusion Criteria: * Histologically confirmed diagnosis of solid tumor or leukemia with documented M3 marrow * Histologic confirmation of intrinsic brain stem tumors not required * Relapsed or refractory disease * No known curative therapy * In patients with CNS tumors, neurologic deficits must be stable for at least the past week * Performance status - Karnofsky 50-100% (\>10 years of age) * Performance status - Lansky 50-100% (≤ 10 years of age) * For patients with solid tumors: * Absolute neutrophil count ≥ 1,000/mm\^3 * Platelet count ≥ 100,000/mm\^3 (transfusion independent) * Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions) * For patients with leukemia: * Platelet count ≥ 20,000/mm\^3 (may receive platelet transfusions) * Hemoglobin ≥ 8.0 g/dL (may receive RBC transfusions) * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * ALT ≤ 2.5 times ULN * Albumin ≥ 2 g/dL * Creatinine clearance OR radioisotope glomerular filtration rate ≥ 70 mL/min * Creatinine based on age as follows: * ≤ 0.8 mg/dL if ≤ 5 years of age * ≤ 1.0 mg/dL if \> 5 years and ≤ 10 years of age * ≤ 1.2 mg/dL if \> 10 years and ≤ 15 years of age * ≤ 1.5 mg/dL if \> 15 years and ≤ 21 years of age * No uncontrolled infection * No prior severe allergy to eggs * No situation that would preclude study participation * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * At least 7 days (or window for adverse effects has passed) since prior biologic therapy and recovered * At least 7 days since prior hematopoietic growth factors * At least 2 months since prior stem cell transplantation and no evidence of graft-vs-host disease * No concurrent hematopoietic growth factors * No concurrent biologic therapy * No concurrent immunotherapy * At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas) and recovered * No other concurrent chemotherapy * No concurrent steroid therapy * At least 2 weeks since prior local palliative radiotherapy (small port) * At least 3 months since prior total body irradiation or craniospinal radiotherapy * At least 3 months since prior radiotherapy to ≥ 50% of the pelvis * At least 6 weeks since prior substantial bone marrow radiotherapy * Recovered from prior radiotherapy * No concurrent radiotherapy * No other concurrent investigational drugs * No other concurrent anticancer agents * No concurrent phenytoin or phenobarbital * No concurrent warfarin
Plan de l'étude
Découvrez tous les traitements administrés dans cette étude, leur description détaillée et ce qu'ils impliquent.Un seul groupe d'intervention est désigné dans cette étude
Cette étude ne comporte pas de groupe placebo.
Groupes de traitement
Groupe I
ExpérimentalObjectifs de l'étude
Objectifs principaux
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 1 site