A Phase II Study of Campath-1H in Children With Acute Lymphoblastic Leukemia in Second or Greater Relapse or Twice Induction Failure
alemtuzumab
+ methotrexate
+ mercaptopurine
Maladies Hématologiques+8
+ Maladies hématologiques et lymphatiques
+ Maladies du Système Immunitaire
Étude thérapeutique
Résumé
Date de début de l'étude : 1 juillet 2004
Date à laquelle le premier participant a commencé l'étude.PRIMARY OBJECTIVES: I. Determine the response rate to alemtuzumab alone and in combination with methotrexate and mercaptopurine in children with acute lymphoblastic leukemia in second or greater relapse or twice induction failure. II. Determine the toxicity of these regimens in these patients. SECONDARY OBJECTIVES: I. Determine the pharmacokinetics of alemtuzumab in these patients. II. Determine the immune response in patients treated with alemtuzumab. III. Determine changes in the number of CD52-positive cells in the blood and marrow of patients treated with alemtuzumab. IV. Determine the rate and timing of clearance of peripheral circulating lymphoblasts in patients treated with these regimens. OUTLINE: This is a multicenter study. Course 1: Patients receive alemtuzumab IV over 2 hours on days 1-5, 8, 10, 12, 15, 17, 19, 22, 24, and 26 in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR), partial remission (PR), or cytolytic PR at day 29, or patients with CNS disease that achieve a CNS 1 or CNS 2 status, proceed to course 2. Courses 2 and 3: Patients receive alemtuzumab IV over 2 hours on days 1, 8, 15, and 22; methotrexate IV continuously over 24 hours on day 1 and then orally once daily on days 8, 15, and 22; and oral mercaptopurine once daily on days 1-28. Patients with a CR or PR at day 29 proceed to course 3. In course 3, patients receive alemtuzumab, methotrexate, and mercaptopurine as in course 2. CNS prophylaxis\*: Patients receive methotrexate intrathecally on day 1 of courses 2 and 3 on day 1 of courses 2 and 3. NOTE: \* CNS-negative patients receive methotrexate intrathecally on day 15 of course 1 and day 1 of courses 2 and 3.
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.25 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.Jusqu'à 30 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: * Diagnosis of acute lymphoblastic leukemia (ALL) * Meets 1 of the following criteria: * Second or subsequent bone marrow relapse * Failed ≥ 2 regimens for remission induction * Patients who relapse while receiving standard ALL maintenance chemotherapy do not require a waiting period prior to study entry * More than 25% blasts in bone marrow aspirate (M3 marrow) * CD52 expression on ≥ 25% of malignant cells at relapse * Philadelphia chromosome-positive patients must have failed prior imatinib mesylate * Performance status - Karnofsky 50-100% (for patients \> 10 years of age) * Performance status - Lansky 50-100% (for patients ≤ 10 years of age) * At least 8 weeks * ALT ≤ 5 times upper limit of normal (ULN) * Bilirubin ≤ 1.5 times ULN * Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min * Creatinine normal for age * Pulse oximetry \> 94% * No evidence of dyspnea at rest * No exercise intolerance * No serious uncontrolled infection * No autoimmune hemolytic anemia * No autoimmune thrombocytopenia * Not pregnant or nursing * No nursing for 3 months after study participation * Negative pregnancy test * Fertile patients must use effective contraception during and for 6 months after study participation * Seizure disorder allowed provided patients are on anticonvulsants and symptoms are well controlled * CNS toxicity ≤ grade 2 * No other serious uncontrolled medical condition (e.g., diabetes) * Recovered from prior immunotherapy * At least 8 weeks since prior biologic agents (e.g., monoclonal antibodies) * More than 1 week since prior growth factor(s) * At least 4 months since prior stem cell transplantation * No evidence of active acute or chronic graft-versus-host disease post allogeneic stem cell transplantation * No prior alemtuzumab or its components * No other concurrent anticancer immunomodulating agents * Recovered from prior chemotherapy * One dose of prior intrathecal (IT) methotrexate, cytarabine, and hydrocortisone; IT cytarabine alone; or IT methotrexate alone allowed as part of initial diagnostic spinal tap * Prior hydroxyurea therapy allowed * No other concurrent anticancer chemotherapy agents * Prior steroid therapy allowed * More than 2 weeks since prior radiotherapy and recovered
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