- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00049569
Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia
Intensive Induction Therapy for Children With Acute Lymphoblastic Leukemia (ALL) Who Experience a Bone Marrow Relapse
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
- Médicament: leucovorine calcique
- Médicament: cyclophosphamide
- Médicament: étoposide
- Médicament: chlorhydrate de doxorubicine
- Médicament: sulfate de vincristine
- Médicament: la cytarabine
- Médicament: pégaspargase
- Médicament: méthotrexate
- Biologique: filgrastim
- Médicament: prednisone
- Médicament: asparaginase
- Médicament: hydrocortisone thérapeutique
- Médicament: mésylate d'imatinib
Description détaillée
PRIMARY OBJECTIVES:
I. To assess the feasibility and safety of using an intensified sequential induction regimen to treat children with acute lymphoblastic leukemia (ALL), who experience an isolated, or combined bone marrow relapse.
II. To determine the potential of this regimen to serve, as a backbone, for the future testing of novel therapeutic agents.
SECONDARY OBJECTIVES:
I. To estimate the remission re-induction rates and four-month event-free survival (EFS) for children, stratified by the duration of first remission.
II. To determine the feasibility of measuring minimal residual disease (MRD) quantitatively in all patients at time points throughout re-induction, and to correlate post-remission events with disease burden during induction.
III. To use deoxyribonucleic acid (DNA) arrays to characterize patterns of gene expression that predict treatment failure, and to compare gene expression profiles at the time of relapse with those at the time of initial diagnosis to gain an understanding of the pathways that may be involved in disease recurrence.
IV. To determine the feasibility of combining intensive re-induction therapy with imatinib mesylate (STI571) for children with a relapse of Philadelphia chromosome positive (Ph+) ALL.
OUTLINE: Patients are randomized to 1 of 2 treatment arms.
ARM I:
Treatment Block 1: Patients receive cytarabine intrathecally (IT) on day 1 and methotrexate IT on days 15 and 29. Patients also receive vincristine intravenously (IV) on days 1, 8, 15, and 22; prednisone orally (PO) twice or thrice daily (BID or TID) on days 1-29; pegaspargase intramuscularly (IM) on days 2, 8, 15, and 22; and doxorubicin IV over 15 minutes on day 1. Ph-positive patients also receive imatinib mesylate PO on days 1-14.
Treatment Block 2: Patients receive methotrexate IT on days 1 and 22, cyclophosphamide IV over 30 minutes and etoposide IV over 2 hours on days 1-5, and filgrastim (G-CSF) subcutaneously (SC) beginning on day 6 and continuing until blood counts recover. Patients also receive methotrexate IV over 24 hours on day 22 followed by leucovorin calcium IV every 6 hours on days 24 and 25. Ph-positive patients receive imatinib mesylate PO on days 1-14.
Treatment Block 3a (Ph-negative patients): Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 2, 8, and 9, asparaginase IM on days 2 and 9, and G-CSF SC beginning on day 10 and continuing until blood counts recover.
Treatment Block 3b (Ph-positive patients): Patients receive cytarabine IV over 3 hours every 12 hours on days 1 and 2, asparaginase IM on day 2, and G-CSF SC beginning on day 3 and continuing until blood counts recover. Patients also receive imatinib mesylate PO on days 1-14.
ARM II:
Treatment Block 1: Patients receive cytarabine IT on day 1 and then methotrexate, cytarabine and hydrocortisone IT (triple intrathecal therapy; TIT) on days 8, 15, 22, and 29. Vincristine, prednisone, pegaspargase, doxorubicin, and imatinib mesylate are administered as in arm I.
Treatment Block 3: Patients receive cytarabine, asparaginase, G-CSF, and imatinib mesylate as in arm I.
Treatment Block 2: Patients receive TIT on days 1 and 22. Patients then receive cyclophosphamide, etoposide, G-CSF, methotrexate IV, leucovorin calcium, and imatinib mesylate as in arm I. After each block is completed, disease is assessed. The next block is started on day 36 if blood counts have recovered and marrow during block 1 is at least M2/M3. Patients are removed from protocol therapy if disease progresses, unacceptable toxicity occurs, marrow is M2/M3 at day 15 of the second administered block of treatment, or cerebrospinal fluid blasts persist after 6 weekly doses of TIT.
After completion of study treatment, patients are followed up for 4 months.
PROJECTED ACCRUAL: A total of 63-126 patients will be accrued for this study within 14 months.
Type d'étude
Inscription (Anticipé)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
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California
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Arcadia, California, États-Unis, 91006-3776
- Children's Oncology Group
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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:
- Patients with acute lymphoblastic leukemia (ALL) in first relapse involving the bone marrow (M3 marrow), with or without associated extramedullary disease; this includes patients who are Philadelphia chromosome-positive
- Shortening fraction of >= 28% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study
- Cumulative prior anthracycline exposure of =< 350 mg/m^2 (each 10 mg/m^2 dose of idarubicin should be calculated as the isotoxic equivalent of 50 mg/m^2 of daunorubicin or adriamycin)
- All patients and/or their parents or legal guardians must sign a written informed consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met
Exclusion Criteria:
- Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular or cytogenetic technique) are not eligible
- Patients with Down syndrome are excluded due to the administration of methotrexate in Block 2
Patients who have undergone prior stem cell transplantation (SCT) are ineligible if:
- They received SCT less than 12 months prior to study entry
- They are still receiving immunosuppression for the treatment of graft-versus-host disease (GVHD)
- They have active fungal infection at time of study entry
- They have had invasive filamentous fungal infection at any time post-SCT
- Pregnant or lactating females are ineligible as the medications used in this protocol could be harmful to unborn children and infants
- Patients with prior isolated extramedullary relapse are ineligible
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Expérimental: Bras je
Voir descriptif détaillé.
|
Étant donné IV
Étant donné IV
Étant donné IV
Étant donné IV
Étant donné IV
Compte tenu de l'informatique
Compte tenu de la messagerie instantanée
Compte tenu de l'informatique
Étant donné SC
Bon de commande donné
Étant donné la messagerie instantanée
Bon de commande donné
|
Expérimental: Arm II
See detailed description.
|
Étant donné IV
Étant donné IV
Étant donné IV
Étant donné IV
Étant donné IV
Compte tenu de l'informatique
Compte tenu de la messagerie instantanée
Compte tenu de l'informatique
Étant donné SC
Bon de commande donné
Étant donné la messagerie instantanée
Compte tenu de l'informatique
Bon de commande donné
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Feasibility assessed by excessive early deaths, induction failures, and early relapses
Délai: Up to 4 months
|
Up to 4 months
|
|
Toxicity assessed using CTC version 2.0
Délai: Up to 4 months
|
Will be tabulated in detail.
|
Up to 4 months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Overall remission reinduction (CR2) rate
Délai: Up to 4 months
|
Up to 4 months
|
|
EFS
Délai: 4 months
|
The Kaplan-Meier method will be used.
|
4 months
|
MRD
Délai: Up to 4 months
|
The percentage of MRD positive patients will be estimated at the end of each block.
Cox regression will be utilized to correlate MRD values with EFS.
|
Up to 4 months
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Feasibility of combining intensive re-induction therapy with imatinib mesylate
Délai: Up to 4 months
|
Will be determined using descriptive statistics due to the small sample size.
|
Up to 4 months
|
Percentage of patients who were able to complete the triple re-induction therapy with imatinib mesylate
Délai: Up to 4 months
|
Will be estimated.
|
Up to 4 months
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Elizabeth Raetz, Children's Oncology Group
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (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
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Leucémie
- Leucémie-lymphome lymphoblastique à cellules précurseurs
- Leucémie, Lymphoïde
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents antiviraux
- Inhibiteurs de la synthèse des acides nucléiques
- Inhibiteurs d'enzymes
- Agents anti-inflammatoires
- Agents antirhumatismaux
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Modulateurs de tubuline
- Agents antimitotiques
- Modulateurs de mitose
- Glucocorticoïdes
- Les hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Agents antinéoplasiques, hormonaux
- Agents protecteurs
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Agents antinéoplasiques phytogéniques
- Inhibiteurs de la topoisomérase II
- Inhibiteurs de la topoisomérase
- Agents dermatologiques
- Micronutriments
- Inhibiteurs de protéine kinase
- Antibiotiques, Antinéoplasiques
- Vitamines
- Agents de contrôle de la reproduction
- Antidotes
- Complexe de vitamine B
- Agents abortifs, non stéroïdiens
- Agents abortifs
- Antagonistes de l'acide folique
- Cyclophosphamide
- Étoposide
- Leucovorine
- Lévoleucovorine
- Prednisone
- Doxorubicine
- Doxorubicine liposomale
- Cytarabine
- Méthotrexate
- Vincristine
- Asparaginase
- Mésylate d'imatinib
- Hydrocortisone
- Hydrocortisone 17-butyrate 21-propionate
- Acétate d'hydrocortisone
- Hémisuccinate d'hydrocortisone
- Pégaspargase
Autres numéros d'identification d'étude
- NCI-2012-01798 (Identificateur de registre: CTRP (Clinical Trial Reporting Program))
- U10CA098543 (Subvention/contrat des NIH des États-Unis)
- COG-AALL01P2
- CDR0000258120
- AALL01P2 (Autre identifiant: CTEP)
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 .
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