- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01132586
Lenalidomide, Cytarabine, and Idarubicin in Treating Patients With Acute Myeloid Leukemia
Phase I Study of Lenalidomide and Conventional Chemotherapy in Acute Myeloid Leukemia
Aperçu de l'étude
Statut
Les conditions
- Leucémie myéloïde aiguë résultant d'un syndrome myélodysplasique antérieur
- Syndrome myélodysplasique déjà traité
- Leucémie myéloïde aiguë récurrente de l'adulte
- Leucémie myéloïde aiguë secondaire
- Leucémie myéloïde aiguë non traitée chez l'adulte
- Syndrome myélodysplasique secondaire
- Syndrome myélodysplasique de Novo
- Leucémie myéloïde aiguë de l'adulte avec Inv(16)(p13.1q22); CBFB-MYH11
- Leucémie myéloïde aiguë de l'adulte avec t(16;16)(p13.1;q22); CBFB-MYH11
- Leucémie myéloïde aiguë liée aux agents alkylants
- Leucémie myéloïde aiguë de l'adulte avec t(9;11)(p22;q23); MLLT3-MLL
- Leucémie promyélocytaire aiguë de l'adulte avec t(15;17)(q22;q12); PML-RARA
- Leucémie myéloïde aiguë de l'adulte avec t(8;21)(q22;q22); RUNX1-RUNX1T1
Description détaillée
PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) of lenalidomide in combination with conventional chemotherapy in two separate cohorts of patients with 1) relapsed or refractory acute myeloid leukemia (AML) and 2) age >= 60 with untreated AML and recommend starting doses for phase II studies of this combination of agents.
SECONDARY OBJECTIVES:
I. To define the qualitative and quantitative toxicities of these combinations of agents in regard to organ specificity, time course, predictability, and reversibility.
II. To document the therapeutic response of these combinations of agents in patients with poor risk AML.
III. To conduct pharmacodynamic studies to investigate the potential mechanism of lenalidomide activity in this trial.
OUTLINE: This is a dose-escalation study of lenalidomide.
INDUCTION:
COHORT I: Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, cytarabine intravenously (IV) continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7.
COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above.
Patients with residual disease on day 18 undergo a second course of induction therapy.
CONSOLIDATION:
COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity.
COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 30 days.
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
-
-
Ohio
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Columbus, Ohio, États-Unis, 43210
- Ohio State University Comprehensive Cancer Center
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
Cohort 1: Patients must be age >= 18 and < 65 with relapsed or refractory AML or high risk myelodysplastic syndrome (MDS); high risk MDS is defined as international prognosis scoring system (IPSS) score of 1.5 or higher; eligible patients will have a score of 1.5 or higher at any time from diagnosis to screening
- Cohort 2: Patients must be age >= 18 with previously untreated AML; favorable risk AML patients < 60 years of age are excluded; these are defined as core binding factor (CBF) AML patients and characterized by cytogenetic or molecular evidence of CBF leukemia; untreated AML patients < 60 years of age must be negative on screening for CBF leukemia by cytogenetic or molecular analysis (Note: Prior therapy for MDS is permitted)
- Patients with secondary AML or therapy-related disease (transformed [t]-AML/MDS) are eligible
- If the patient has co-morbid medical illness, life expectancy attributed to this must be greater than 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Total bilirubin < 2.0 mg/dL
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 2.5 times upper limit of normal
- Creatinine < 2.0 mg/dL AND creatinine clearance (calculated) >= 50 mL/min
- Left ventricular ejection fraction (LVEF) >= 40%
- Patients who have previously received lenalidomide, idarubicin, and/or cytarabine are eligible provided that the combination of the 3 agents has never before been administered, and that no lenalidomide has been administered for at least 6 months
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a minimum sensitivity of at least 25 mIU/mL within 10-14 days prior to and again within 24 hours of starting lenalidomide and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide; FCBP must also agree to ongoing pregnancy testing; men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy; these methods of birth control must be used for the duration of study participation and for 28 days after lenalidomide discontinuation; all patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure
- Ability to understand and willingness to sign the written informed consent document
Exclusion Criteria:
- Patients who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study, or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients who have taken lenalidomide within the last 6 months
- Patients receiving any other investigational agents or patients that have received other investigational agents within 14 days of enrollment
- Patients with active central nervous system disease or with granulocytic sarcoma as sole site of disease
- Patients with history of medically serious allergic reactions or non-hematologic toxicities attributed to the agents in this trial such as lenalidomide or thalidomide or compounds of similar chemical or biologic composition that are not easily managed, or patients with a history of cerebellar toxicity to cytarabine
- Patients with the following will be excluded: uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; patients with medical comorbidities that will preclude safety evaluation of the combination should not be enrolled
- Patients with serious medical or psychiatric illness likely to interfere with participation in this clinical study
- Pregnant women or women who are breastfeeding; additional pregnancy testing before, during, and after lenalidomide treatment is required, as well as requirements for contraception before, during, and after lenalidomide treatment
- Patients with advanced malignant solid tumors are excluded; patients with active additional hematologic malignancies are excluded
- Patients with a history of neurologic toxicity with cytarabine are excluded
- As infection is a common feature of AML, patients with active infection are permitted to enroll provided that the infection is under control; patients with uncontrolled infection shall not be enrolled until infection is treated and brought under control
- Known human immunodeficiency virus (HIV)-positive patients are ineligible; appropriate studies will be undertaken in HIV + patients once safety of the combination has been demonstrated
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: N / A
- Modèle interventionnel: Affectation à un seul groupe
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Treatment (lenalidomide, cytarabine, idarubicin)
INDUCTION: COHORT I: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 96 hours on days 5-8, and idarubicin IV over 1 hour on days 5-7. COHORT II: Patients receive lenalidomide PO QD on days 1-21, cytarabine IV continuously over 24 hours on days 5-11, and idarubicin as above. Patients with residual disease on day 18 undergo a second course of induction therapy. CONSOLIDATION: COHORT I: Patients receive lenalidomide PO QD on days 1-14, idarubicin IV over 1 hour on days 5-6, cytarabine IV continuously on days 5-7. Treatment continues for 1 course in the absence of disease progression or unacceptable toxicity. COHORT II: Patients 2 receive 4 courses of consolidation therapy comprising lenalidomide PO QD on days 1-14 and cytarabine IV every 12 hours on days 5, 7, and 9. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. |
Études corrélatives
Études corrélatives
Autres noms:
Étant donné IV
Autres noms:
Bon de commande donné
Autres noms:
Étant donné IV
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Délai |
|---|---|
|
MTD of lenalidomide, determined according to incidence of dose-limiting toxicity (DLT) graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Délai: 28 days
|
28 days
|
Mesures de résultats secondaires
Mesure des résultats |
Délai |
|---|---|
|
Qualitative and quantitative toxicities, graded using NCI CTCAE version 4.0
Délai: Up to 30 days post-treatment
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Up to 30 days post-treatment
|
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Therapeutic response, assessed using International Working Group criteria
Délai: Up to 30 days post-treatment
|
Up to 30 days post-treatment
|
|
Pharmacodynamic studies, including micro-ribonucleic acid (miRNA)-181 family and target gene expression, CCAAT/enhancer binding protein (C/EBP), alpha gene (CEBPA) expression, and genes involved in erythroid differentiation
Délai: Baseline, day 5, and day 28
|
Baseline, day 5, and day 28
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: William Blum, Ohio State University Comprehensive Cancer Center
Publications et liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Processus pathologiques
- Tumeurs par type histologique
- Tumeurs
- Maladie
- Maladies de la moelle osseuse
- Maladies hématologiques
- Processus néoplasiques
- Conditions précancéreuses
- Syndrome
- Syndromes myélodysplasiques
- Leucémie
- Leucémie myéloïde
- Leucémie, myéloïde, aiguë
- Métastase néoplasmique
- Préleucémie
- Leucémie, promyélocytaire, aiguë
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs d'enzymes
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Inhibiteurs de l'angiogenèse
- Agents modulateurs de l'angiogenèse
- Substances de croissance
- Inhibiteurs de croissance
- Antibiotiques, Antinéoplasiques
- Lénalidomide
- Cytarabine
- Idarubicine
Autres numéros d'identification d'étude
- NCI-2011-01375 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- P30CA016058 (Subvention/contrat des NIH des États-Unis)
- UM1CA186712 (Subvention/contrat des NIH des États-Unis)
- 8455 (Autre identifiant: CTEP)
- U01CA076576 (Subvention/contrat des NIH des États-Unis)
- OSU-10016
- CDR0000673883
- OSU 10016 (Autre identifiant: Ohio State University Comprehensive Cancer Center)
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