A Phase 1/2 Dose and Schedule Finding Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of Oral Azacitidine (CC-486) in Subjects With Acute Myelogenous Leukemia and Myelodysplastic Syndromes After Allogeneic Hematopoietic Stem Cell Transplantation
CC-486
Maladies de la moelle osseuse+6
+ Maladies Hématologiques
+ Maladies hématologiques et lymphatiques
Étude thérapeutique
Résumé
Date de début de l'étude : 25 octobre 2013
Date à laquelle le premier participant a commencé l'étude.This is an open-label, multicenter study of oral azacitidine in MDS or AML patients who have undergone allogeneic HSCT. The study consists of three phases: Screening, Treatment and Follow-up. During the Screening phase, the study doctor will do tests to see if the patient is suitable for this study. The patients meeting protocol-specified entry criteria will enter the treatment phase and be assigned to receive one of the oral azacitidine cohorts. The dosing group of 200 mg QD on Days 1 to 7 will be evaluated first (ie, Cohort 1). In the event that unacceptable toxicity occurs in Cohort 1, then oral azacitidine may be evaluated at lower dose levels (eg, 150 mg). If the dosing regimen is confirmed to be safe in Cohort 1, other cohorts will be evaluated sequentially. During the treatment phase, patients will be monitored closely for safety and tolerability. Dosing interruption or delay, dose or schedule reduction, intra-subject dose/schedule escalation or re-escalation may occur on the basis of protocol-specified dosing adjustment guidelines. Safety will be monitored throughout the study at predetermined intervals and as clinically indicated by vital signs, physical examination, performance status, laboratory tests and evaluation of adverse events. The patient can continue to receive the study treatment for up to 12 months provided that they benefit from the study treatment and all protocol-specified criteria are met. However, the patient may receive the study treatment for less than 12 months due to adverse event, disease recurrence or progression. When the study treatment is discontinued, all patients who have received at least one dose of oral azacitidine will be asked to see the study doctor for the treatment discontinuation visit. Thereafter, all patients discontinued from the study treatment will enter the Follow-up phase for safety and survival follow up.
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.31 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.À partir de 18 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 Myelodysplastic Syndromes or Acute Myeloid Leukemia undergoing allogeneic hematopoietic stem cell transplantation with either peripheral blood or bone marrow as the source of hematopoietic stem cells At the time of allogeneic HSCT: No prior allogeneic HSCT; and No more than 1 antigen mismatch at Human Leukocyte Antigen (HLA)-A, -B, -C, -DRB1 or -DQB1 locus for either related or unrelated donor; and Bone marrow blast < 20% if MDS or ≤ 10% if AML; and Peripheral blood blast ≤ 5% Be able to start study drug between 42 to 84 days following allogeneic HSCT Post transplant bone marrow blast count ≤ 5% confirmed within 21 days prior to starting study therapy Adequate engraftment within 14 days prior to starting study therapy: Absolute Neutrophil count (ANC) ≥ 1.0 x 10^9/L without daily use of myeloid growth factor; and Platelet count 75 x 10^9/L without platelet transfusion within one week. Adequate organ function: Serum aspartate transaminase (AST) and alanine transaminase (ALT) < 3 x upper limit of normal (ULN) Serum bilirubin < 2 x ULN Serum creatinine < 2 x ULN Adequate coagulation (Prothrombin time [PT] ≤ 15 seconds, Partial thromboplastin time (PTT) ≤ 40 seconds, and/or International normalized ratio [INR] ≤ 1.5) Have a negative serum pregnancy test (sensitivity of at least 25 mIU/mL at screening). Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 Must agree to follow protocol-specified pregnancy precautions Exclusion Criteria: Use of any of the following after transplantation and prior to starting oral azacitidine: Chemotherapeutic agents for chemotherapy Investigational agents/therapies Azacitidine, decitabine or other demethylating agents Lenalidomide, thalidomide and pomalidomide Active Graft-versus-host disease (GVHD) grade II or higher Any evidence of gastrointestinal (GI) GVHD Concurrent use of corticosteroids equivalent of prednisone at a dose > 0.5 mg/kg Known active viral infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) Active uncontrolled systemic fungal, bacterial or viral infection Presence of malignancies, other than MDS or AML, within the previous 12 months Significant active cardiac disease within the previous 6 months
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
Objectifs secondaires
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 5 sites
Memorial Sloan-Kettering Cancer Center.
New York, United StatesOuvrir Memorial Sloan-Kettering Cancer Center. dans Google MapsUniversity Hospitals Cleveland Medical Center
Cleveland, United StatesMD Anderson Cancer Center The University of Texas
Houston, United StatesFred Hutchinson Cancer Research Center
Seattle, United States