- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00085423
Cyclophosphamide, Fludarabine, and High-Dose Interleukin-2 in Treating Patients With Metastatic Melanoma
High Dose Interleukin-2 (IL-2) Therapy In "Lymphodepleted Primed" Patients With Metastatic Melanoma
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill tumor cells and may help a person's immune system recover from the side effects of chemotherapy.
PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine together with high-dose interleukin-2 works in treating patients with metastatic melanoma.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
OBJECTIVES:
Primary
- Determine the objective response rate in lymphodepleted patients with metastatic melanoma treated with cyclophosphamide, fludarabine, and high-dose interleukin-2.
- Determine the feasibility of this regimen in these patients.
Secondary
- Determine the quality and quantity of lymphocyte recovery in these patients during and after treatment with this regimen.
- Determine time to disease progression and survival in patients treated with this regimen.
OUTLINE: This is an open-label, multicenter study.
Patients receive lymphodepleting therapy comprising cyclophosphamide IV over 1 hour on days 1 and 2 and fludarabine IV over 30 minutes on days 3-7. Patients then receive high-dose interleukin-2 IV every 8 hours (14 doses) on days 8-12 and 22-26. Patients also receive sargramostim (GM-CSF) subcutaneously beginning on day 8 and continuing until blood counts recover. Treatment continues in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months.
PROJECTED ACCRUAL: A total of 18-33 patients will be accrued for this study.
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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New Hampshire
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Lebanon, New Hampshire, États-Unis, 03756-0002
- Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical 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:
- Histologically confirmed melanoma
- Metastatic disease
- Measurable disease
- No history of brain metastases
- Over 18
- Karnofsky 60-100%
- Life expectancy At least 12 weeks
- Hematopoietic
- Absolute neutrophil count ≥ 1,000/mm^3
- Platelet count ≥ 75,000/mm^3
- Hemoglobin ≥ 8.5 g/dL
- aspartate aminotransferase ≤ 2 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
- Bilirubin ≤ 2 times ULN (except for patients with Gilbert's syndrome)
- Hepatitis B and C negative
- Creatinine ≤ 2.0 times ULN
- Creatinine clearance ≥ 50 mL/min
- Cardiovascular
- Ejection fraction ≥ 50%
- No evidence of congestive heart failure
- No symptoms of coronary artery disease
- No serious cardiac arrhythmias
- No myocardial infarction within the past 6 months
- Cardiac stress test negative or of low probability for patients > 40 years of age OR who have had prior myocardial infarction > 6 months ago
- Pulmonary Forced expiratory volume 1 ≥ 2.0 liters OR at least 75% of predicted for height and age
- Diffusing capacity of lung for carbon monoxide ≥ 60%
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
Exclusion Criteria:
- No uncontrolled diabetes
- No history of autoimmune disease
- No active infection
- No other concurrent significant illness that would preclude study participation
- No other malignancy within the past 5 years except nonmelanoma skin cancer or non-invasive cancer (e.g., carcinoma in situ of the cervix, superficial bladder cancer without local recurrence, or carcinoma in situ of the breast)
- At least 4 weeks since prior immunotherapy and recovered
- No other concurrent anticancer biologic agents
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas) and recovered
- No concurrent chemotherapy
- At least 4 weeks since prior steroid therapy
- No concurrent corticosteroids
- At least 4 weeks since prior radiotherapy and recovered
- No concurrent radiotherapy
- At least 4 weeks since prior surgery and recovered
- No concurrent immunosuppressive therapy
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: IL-2, CTX, fludarabine, GM-CSF
Aldesleukin (IL-2), cyclophosphamide, fludarabine phosphate, sargramostim
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‡Interleukin-2 (aldesleukin) IV (600,000 U/kg; Chiron, Emeryville, CA): two 5-day courses on days 8 and 22. Interleukin-2 was given over 15 minutes every 8 hours.
Goal is 14 doses/5-day course
Autres noms:
GM-CSF was given subcutaneously daily from day 8 until absolute granulocyte count exceeds 5,000 cells/mL for 2 consecutive days.
Autres noms:
Cyclophosphamide (60 mg/kg/d; Baxter, Deerfield, IL) intravenously (IV) for 2 days with sodium 2- mercaptoethanesulfonate (Mesna; Sicor, Irvine, CA) at 20% of cyclophosphamide dose IV 15 minutes before and 40% of the cyclophosphamide dose orally at 2 and 6 hours after the initiation of chemotherapy.
Autres noms:
Fludarabine IV (25 mg/M2/day)-five daily doses from Day 3
Autres noms:
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Number of partiCIPANTS WITH OBJECTIVE RESPONSE AS MEASURED BY RECIST
Délai: Response at 12 weeks
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Objective response as measured by radiological and physical examination using RECIST criteria.
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Response at 12 weeks
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Number of Participants With Lymphocyte Recovery as Measured by Blood Count
Délai: on days 1-15, weekly for 2 weeks, and then every 2-3 months
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Lymphocyte recovery to a greater than 1000 cells/mcL was determined by differential peripheral blood cell counts on sequential days as noted in time frame.
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on days 1-15, weekly for 2 weeks, and then every 2-3 months
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Time to Progression as Measured by RECIST
Délai: From date of randomization until the first date of documented progression or date of death from any cause, which ever came first, assessed up till 100 months
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Clinical outcome used the National Cancer Institute's Response Evaluation Criteria in Solid Tumors (RECIST)1.0.
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From date of randomization until the first date of documented progression or date of death from any cause, which ever came first, assessed up till 100 months
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Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chaise d'étude: Marc S. Ernstoff, MD, Norris Cotton 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
Mots clés
Termes MeSH pertinents supplémentaires
- Tumeurs par type histologique
- Tumeurs
- Tumeurs neuroectodermiques
- Tumeurs, cellules germinales et embryonnaires
- Tumeurs, tissu nerveux
- Tumeurs neuroendocrines
- Nevi et mélanomes
- Mélanome
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Agents du système nerveux périphérique
- Agents antiviraux
- Agents anti-VIH
- Agents antirétroviraux
- Analgésiques
- Agents du système sensoriel
- Analgésiques, non narcotiques
- Agents antirhumatismaux
- Antimétabolites, Antinéoplasique
- Antimétabolites
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents antinéoplasiques, alkylants
- Agents d'alkylation
- Agonistes myéloablatifs
- Aldesleukine
- Cyclophosphamide
- Fludarabine
- Phosphate de fludarabine
- Sargramostim
- Interleukine-2
- Molgramostim
Autres numéros d'identification d'étude
- CDR0000370788
- P30CA023108 (Subvention/contrat des NIH des États-Unis)
- DMS-0320 (Autre identifiant: Dartmouth-Hitchcock)
- DMS-16531 (Autre identifiant: Dartmouth-Hitchcock)
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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