A Phase II Study of Dose-Adjusted Etoposide, Prednisone, Vincristine, Cyclophosphamide, and Doxorubicin Plus Asparaginase (DA-EPOCH-A) for Adults With Acute Lymphoblastic Leukemia/Lymphoma
Asparaginase
+ Cyclophosphamide
+ Doxorubicin Hydrochloride
Lymphome de Burkitt+20
+ Infections par virus ADN
+ Maladies Hématologiques
Étude thérapeutique
Résumé
Date de début de l'étude : 1 juillet 2018
Date à laquelle le premier participant a commencé l'étude.PRIMARY OBJECTIVES: I. To determine the efficacy of dose-adjusted etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride plus asparaginase (DA-EPOCH-A) in adults with acute lymphoblastic leukemia/lymphoma (ALL). SECONDARY OBJECTIVES: I. To evaluate the safety and feasibility of this regimen. OUTLINE: Patients receive etoposide, doxorubicin hydrochloride, and vincristine sulfate intravenously (IV) continuously over days 1-4, cyclophosphamide IV over 1 hour on day 5, and prednisone orally (PO) twice daily (BID) on days 1-5. Patients also receive asparaginase intramuscularly (IM) or IV over 1-2 hours every 2-3 days, beginning day 7 of each course. Patients who are cluster of differentiation (CD)20 positive and Philadelphia chromosome negative also receive rituximab IV on day 1 or 5. Patients who are Philadelphia chromosome positive also receive imatinib mesylate PO on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
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.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: * Patients must have a confirmed diagnosis of either B- or T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma that is either: * Arm A: Initially diagnosed at age 40 or later, OR * Arm B: Relapsed after or failed to respond to \>= 1 previous chemotherapy regimen * The regimen under study must constitute a reasonable therapeutic option * Presence of \>= 5% abnormal blasts in the bone marrow * Patients with prior allogeneic hematopoietic cell transplantation (HCT) must be at least 90 days post-HCT and must be on =\< 20 mg of prednisone (or equivalent dose of an alternative corticosteroid) for treatment/prevention of graft-vs-host disease * Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN; unless attributable to Gilbert's disease or other causes of inherited indirect hyperbilirubinemia, at which point total bilirubin must be =\< 2.5 x ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional ULN * Note: Patients with liver test abnormalities attributable to hepatic involvement by ALL will be permitted if the total bilirubin is =\< 3.0 x ULN and ALT/AST are =\< 5.0 x ULN * Creatinine =\< 1.5 mg/dL; however, patients with a creatinine \> 1.5 mg/dL but with a calculated creatinine clearance of \> 60 ml/min, as measured by the Modification of Diet in Renal Disease (MDRD) equation, will be eligible * Measurement of left ventricular ejection fraction (LVEF) should be performed in patients with prior anthracycline exposure or known history of arrhythmia or structural heart disease; in these cases, LVEF must be \>= 40% * As patients with ALL frequently have cytopenias, no hematologic parameters will be required for enrollment or to receive the first cycle of treatment; however, adequate recovery of blood counts will be required to receive subsequent cycles * Per good clinical practice, any toxicity related to prior therapies that, in the opinion of the investigator, would potentially be worsened with DA-EPOCH-A +/- imatinib (imatinib mesylate) +/- rituximab, should be resolved to grade 1 or less * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Women of childbearing potential must have a negative pregnancy test and must agree to the use of effective contraception while on treatment; men must also agree to the use of effective contraception while on treatment * Ability to give informed consent and comply with the protocol * Anticipated survival of at least 3 months Exclusion Criteria: * Patients with Burkitt lymphoma/leukemia * Patients must not have received chemotherapy within 14 days of enrollment, with the two following exceptions: * Routine systemic maintenance therapy (e.g., Abelson murine leukemia viral oncogene homolog 1 \[ABL\] kinase inhibitor, methotrexate, 6-mercaptopurine, vincristine, etc.) and intrathecal/intraventricular therapy * Systemic therapy for the acute management of hyperleukocytosis or acute symptoms (e.g., corticosteroids, cytarabine, etc.) * May not have prior malignancies unless the expected survival is at least 2 years * For patients with Philadelphia chromosome positive (Ph+) ALL, they must not have progressed within 3 months of receiving imatinib or have a documented ABL kinase mutation known to confer resistance to imatinib (e.g., T315I) * Patients with persistent grade 2 or higher peripheral sensory or motor neuropathy of any cause * Patients with isolated extramedullary disease or with parenchymal central nervous system (CNS) disease * Known hypersensitivity or intolerance to any of the agents under investigation * Human immunodeficiency virus (HIV) positive or evidence of infection with hepatitis B or C virus, as defined by any of the following criteria (if patients have not previously been tested for the following, these will be conducted during screening): * HIV antibody positive * Hepatitis B surface antigen or core antibody positive * Hepatitis C antibody positive * Other medical or psychiatric conditions that in the opinion of the investigator would preclude safe participation in the protocol * May not be pregnant or nursing
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 1 site
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, United StatesOuvrir Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium dans Google Maps