- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00620321
A Study of LY2181308 Sodium in Patients With Relapsed or Refractory Acute Myeloid Leukemia
26 août 2019 mis à jour par: Eli Lilly and Company
An Open-Label Phase 2 Trial of LY2181308 Sodium Administered in Combination With Idarubicin and Cytarabine to Patients With Refractory or Relapsed Acute Myeloid Leukemia
The purpose of this study is to understand the safety profile of LY2181308 sodium administered in combination with idarubicin and cytarabine to patients with relapsed or refractory acute myeloid leukemia (AML).
Aperçu de l'étude
Statut
Complété
Les conditions
Intervention / Traitement
Type d'étude
Interventionnel
Inscription (Réel)
24
Phase
- Phase 2
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Michigan
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Ann Arbor, Michigan, États-Unis, 48105
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Texas
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Houston, Texas, États-Unis, 77030
- For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
La description
Inclusion Criteria:
- Patients who have a diagnosis of acute myeloid leukemia that is relapsed or refractory to at least 1 prior treatment for leukemia, or patients with chronic myeloid leukemia (CML) who are in myeloid blast crisis which have failed at least 1 previous tyrosine kinase inhibitor (TK1). A baseline bone marrow assessment is required less than or equal to 96 hours prior to the first dose of study drug.
- Must have discontinued all previous therapies for cancer, including chemotherapy, radiotherapy, immunotherapy, cancer related hormone therapy, or other investigational therapy for at least 21 days for myelosuppressive agents (such as cytarabine, daunorubicin, and gemtuzumab ozogamicin) or 14 days for non-myelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (such as neurotoxicity, diarrhea, and mucositis) except for residual myelosuppression and alopecia. Hydroxyurea is permitted to control the peripheral blast cell count, but must be stopped at least 24 hours before study drug administration.
- Must have adequate organ function.
- Females must have a negative pregnancy test. Male and female patients must agree to use a reliable method of birth control during and for 6 months following the last dose of study drug.
- Patients must be at least 18 years old.
Exclusion Criteria:
- Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication within 14 or 21 days of the initial dose of study drug for a non-myelosuppressive or myelosuppressive agent, respectively.
- Patients with acute promyelocytic leukemia (APML).
- Major surgery within 4 weeks of study enrollment.
- Patients with serious pre-existing medical conditions (at the discretion of the investigator). Because of the known cardiac toxicity of anthracyclines, patients with pre-existing ejection fraction (EF) less than or equal to 45% should not participate in this study. No patient should exceed the maximum exposure of anthracycline doses (for example, idarubicin greater than 120 mg/m²).
- Patients with a second malignancy that could affect the interpretation of the results.
- Patients with leukemic involvement of the central nervous system (CNS) by spinal fluid cytology or imaging.
- Patients with known coagulopathy or bleeding disorder, other than leukemia related thrombocytopenia. Patients with severe of life threatening bleeding refractory to platelet transfusions are also excluded.
- Concomitant anticoagulant therapy (with the exception of heparinized saline to maintain the patency of central venous catheters).
- Women who are pregnant or breast feeding.
- Patients with a known hypersensitivity to oligonucleotides, idarubicin, and/or cytarabine.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
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 |
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Expérimental: LY2181308 sodium, idarubicin, cytarabine
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750 milligrams (mg) is administered as a 3-hour intravenous infusion on Days 1, 2, 3, 8, 15, 22 of Cycle 1 (28 days) and Days 1, 8, 15, 22 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.
1.5 grams per square meter (g/m²) will be administered as a 4-hour intravenous infusion on Days 3, 4, 5 of Cycle 1 (28 days) and Days 1, 2, 3 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.
12 milligrams per square meter (mg/m²) will be administered as a 30-minute intravenous infusion on Days 3, 4, 5 of Cycle 1 (28 days) and on Days 1, 2, 3 of Cycle 2 (28 days) until disease progression or unacceptable toxicity develops.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Number of Participants With Adverse Events (Safety Profile)
Délai: Start of treatment to study completion up to 6.7 months
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Data are presented as number of participants who experienced serious adverse events (SAE) and possibly drug-related treatment-emergent adverse events (TEAE) during the study including the 21-day follow-up period.
A summary of serious adverse events and other nonserious adverse events regardless of causality is located in the Reported Adverse Events section.
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Start of treatment to study completion up to 6.7 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Percentage of Participants With Response to LY2181308 Sodium in Combination With Idarubicin and Cytarabine (Remission Rates)
Délai: Baseline to progression of disease or death up to 6 months
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Response is complete remission (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) + cytoreduction.
CR: fewer than 5% blasts based on a cell count of at least 200 cells from a bone marrow aspirate containing bone marrow spicules, in the setting of peripheral blood recovery to: platelets ≥100x10⁹/liter (L), neutrophils ≥10⁹/L.
PR: defined as a decrease of at least 50% in blast count on the bone marrow aspirate; or cytoreduction (defined as a decrease in blast count not meeting the criteria for a PR or CR).
Response rate is calculated as a total number of participants with CR or CRi or PR or cytoreduction divided by the total number of participants treated multiplied by 100.
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Baseline to progression of disease or death up to 6 months
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Relapse-Free Survival
Délai: Baseline to progression of disease or death up to 6 months
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Relapse-Free Survival was defined as the time from first objective status assessment of complete remission (CR) or CR with incomplete blood count recovery (CRi) or partial remission (PR) or cytoreduction to the first time of disease progression or death as a result of any cause.
CR: fewer than 5% blasts based on a cell count of at least 200 cells from a bone marrow aspirate containing bone marrow spicules, in the setting of peripheral blood recovery to: platelets ≥100x10⁹/liter (L), neutrophils ≥10⁹/L.
PR: defined as a decrease of at least 50% in blast count on the bone marrow aspirate; or cytoreduction (defined as a decrease in blast count not meeting the criteria for a PR or CR).
There were too few participants who had a documented progression of disease or death event amongst the participants with a response of CR, CRi, PR or cytoreduction to conduct the time-to-event analysis, thus the relapse-free survival was not analyzed.
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Baseline to progression of disease or death up to 6 months
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Area Under the Curve of LY2181308 Over the Dosing Interval
Délai: Day 3: 0,12,24,36,48,60,72,84,96,108,120,132 hours
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Area under the curve of LY2181308 over the dosing interval
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Day 3: 0,12,24,36,48,60,72,84,96,108,120,132 hours
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Pharmacodynamics: Number of Participants With Survivin Protein Expression
Délai: 6 Months
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Pharmacodynamics: Number of participants with Survivin Protein Expression.
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6 Months
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Change From Baseline in Survivin Index at Day 2
Délai: Baseline, Day 2
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Data presented are the ratio of Day 2 survivin index to the baseline survivin index.
Survivin is a protein expressed in tumor cells, including acute myeloid leukemia (AML), which regulates mitosis and prevents tumor cell death.
Survivin index was calculated as ([blast survivin mean equivalent fluorochrome (MEFL) - blast isotypic control MEFL]/blast isotypic control MEFL).
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Baseline, Day 2
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Autres mesures de résultats
Mesure des résultats |
Description de la mesure |
Délai |
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Number of Participants Who Died Due to Progressive Disease or Unknown Cause During the 21 Days Post Study Treatment Follow-Up
Délai: Study treatment discontinuation up to 21 days post study treatment discontinuation
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Deaths due to progressive disease (PD) and unknown cause are not considered adverse events.
Deaths due to PD and unknown cause occurring during the 21-day follow-up period after treatment discontinuation are reported here and for those occurring while participants were on treatment are reported in the Participant Flow.
Deaths due to serious adverse events occurred during the study including the 21-day follow-up period are reported in the Reported Adverse Events section.
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Study treatment discontinuation up to 21 days post study treatment discontinuation
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Les enquêteurs
- Directeur d'études: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT-5 hours, EST), Eli Lilly and Company
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 mars 2008
Achèvement primaire (Réel)
1 janvier 2010
Achèvement de l'étude (Réel)
1 janvier 2010
Dates d'inscription aux études
Première soumission
4 février 2008
Première soumission répondant aux critères de contrôle qualité
11 février 2008
Première publication (Estimation)
21 février 2008
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
9 septembre 2019
Dernière mise à jour soumise répondant aux critères de contrôle qualité
26 août 2019
Dernière vérification
1 août 2019
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Leucémie
- Leucémie myéloïde
- Leucémie, myéloïde, 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
- Antibiotiques, Antinéoplasiques
- Cytarabine
- Idarubicine
Autres numéros d'identification d'étude
- 11631
- H8Z-MC-JACU (Autre identifiant: Eli Lilly and Company)
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
OUI
Description du régime IPD
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Délai de partage IPD
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later.
Data will be indefinitely available for requesting.
Critères d'accès au partage IPD
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Type d'informations de prise en charge du partage d'IPD
- PROTOCOLE D'ÉTUDE
- SÈVE
- RSE
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
Essais cliniques sur Leucémie myéloïde aiguë
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Shenzhen Second People's HospitalRecrutementLeucémie | Myéloïde | Chronique | BCR-ABL (Breakpoint Cluster Region-abelson Murine Leukemia) | PositifChine
Essais cliniques sur LY2181308 sodium
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Eli Lilly and CompanyComplétéCancer du poumon non à petites cellulesItalie, États-Unis, Allemagne, Pologne, Belgique, Royaume-Uni
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Institut d'Anesthesiologie des Alpes MaritimesUniversité de Nice Sophia Antipolis; Medical University of GrenobleComplété
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University of DelawareComplétéPression artérielle | Réactivité cérébrovasculaireÉtats-Unis
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University of DelawareComplété
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Radboud University Medical CenterInconnueDiabète de type 1 | Ignorance de l'hypoglycémiePays-Bas
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Austin HealthComplétéSyndrome de réponse inflammatoire systémique | Insuffisance rénale | OligurieAustralie
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Medical University of GrazComplétéCrise cardiaqueL'Autriche
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Osaka General Medical CenterComplétéProcédure coronarienne urgenteJapon
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Lars Wiuff AndersenUniversity of AarhusRecrutement