- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00150462
Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies
A Phase I Study of the Safety and Pharmacokinetics of Escalating Intravenous Doses of the Proteasome Inhibitor PR-171 in Patients With Hematological Malignancies
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- La phase 1
Contacts et emplacements
Lieux d'étude
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California
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Beverly Hills, California, États-Unis, 90211-1850
- Tower Cancer Research Foundation
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Florida
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Tampa, Florida, États-Unis, 33612
- H. Lee Moffitt Cancer Center and Research Institute
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New York
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New York, New York, États-Unis, 10021
- Memorial Sloan Kettering Cancer Center
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New York, New York, États-Unis, 10021
- Weil Medical College of Cornell University
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New York, New York, États-Unis, 10032
- Herbert Irving Comprehensive Cancer Center, Columbia University
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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:
- Written informed consent in accordance with federal, local, and institutional guidelines
- Males and females ≥18 years of age
Histologically confirmed diagnosis of one of the hematologic malignancies below:
- Multiple myeloma (MM)
- Non-Hodgkin's lymphoma (NHL)
- Waldenström's Macroglobulinemia (WM)
- Hodgkin's disease (HD)
- Subjects who are refractory or relapsed following at least two prior therapies
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
- Adequate cardiovascular function without symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction in the previous six months
- Adequate hepatic function, with bilirubin < 2.0 times the upper limit of normal, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) of < 3.0 times the upper limit of normal
Total white blood cell (WBC) count ≥ 2,000/mm³, absolute neutrophil count (ANC) ≥ 1000/mm³, hemoglobin ≥ 8.0 g/dL, and platelet count ≥ 50,000/mm³
- Screening ANC should be independent of granulocyte colony stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) support for ≥ 1 week and of pegylated G-CSF for ≥ 2 weeks)
- Subjects receiving supportive care including erythropoietin, darbepoetin and/or bisphosphonates can continue to do so, but must be transfusion independent; subjects receiving erythropoietic support must remain on the same dose for the first 28 days of study participation
- An estimated creatinine clearance of ≥ 30 mL/min, calculated using the formula of Cockroft and Gault
- Serum creatinine ≤ 2.0 mg/dL
- Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
- Female subjects of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test. Male subjects must use an effective barrier method of contraception throughout the study and for three months following the last dose if sexually active with a female of child-bearing potential.
Exclusion Criteria:
- Female subjects who are pregnant or lactating
- Subjects who are transfusion dependent
- Subjects with NHL or HL who have received steroid therapy in the previous seven days
- Subjects with MM or Waldenström's Macroglobulinemia who have received steroid therapy in the previous three weeks, except for MM subjects in the Carfilzomib + DEX Expansion Cohort, where previous treatment with dexamethasone will be allowed. The dose and schedule of administration of dexamethasone will be adjusted to that used in the protocol
- Radiation, chemotherapy, or immunotherapy in the previous four weeks, or subjects who, in the judgment of the Investigator, have not recovered from the effects of previous therapy
- For the Dose Escalation period, subjects who have received prior radioimmunotherapy with anti-cluster of differentiation (CD)20 monoclonal antibodies such as Bexxar® or Zevalin®; subjects treated with these products will be allowed in the Dose Expansion period
- Subjects who have received allogeneic stem cell transplant therapy
- Subjects with NHL or HL who have received autologous stem cell transplant therapy and have relapsed within 100 days of therapy
- Rituxan therapy within three months before Day 1 unless there is evidence of disease progression
- Major surgery within three weeks before Day 1
- Congestive heart failure (CHF) (New York Heart Association class III to IV)
- Acute active infection requiring systemic antibiotics, antivirals, or antifungals within two weeks prior to first dose
- Subjects who are known or suspected of having human immunodeficiency virus (HIV) infection or who are HIV seropositive
- Active hepatitis A, B, or C infection; or positive for Hepatitis C ribonucleic acid (RNA) or hepatitis B antigen
- Non-hematologic malignancy within the past three years except a) adequately treated basal cell or squamous cell skin cancer, b) carcinoma in situ of the cervix, or c) prostate cancer with stable prostate specific antigen (PSA) levels for three years
- Subjects with treatment-related myelodysplastic disorder
- Subjects with known brain metastasis (active central nervous system [CNS] disease only)
- Serious psychiatric or medical conditions that could interfere with treatment
- Participation in an investigational therapeutic study within one month prior to Day 1
- Significant neurotoxicity (Grade 2 or higher with pain) at the time of study initiation
- Concurrent therapy with approved or investigative anticancer therapeutics
- Subjects with previous hypersensitivity to bortezomib injection
- Subjects with contraindications to receiving allopurinol
- Subjects in whom the required program of oral and intravenous fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment
- Subjects with known or suspected amyloidosis
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- 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: CFZ 1.2 mg/m²
Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 2.4 mg/m²
Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 4.0 mg/m²
Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 6.0 mg/m²
Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 8.4 mg/m²
Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 11.0 mg/m²
Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 15.0 mg/m²
Participants received carfilzomib 115.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 20.0 mg/m²
Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 27.0 mg/m²
Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 20/27 mg/m²
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
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Administered as an IV bolus dose
Autres noms:
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Expérimental: CFZ 20/27 mg/m² + DEX
Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e.
40 mg weekly).
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Administered as an IV bolus dose
Autres noms:
Administered orally prior to carfilzomib
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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 Dose-limiting Toxicities (DLTs)
Délai: 28 days
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A DLT was defined as any of the following occurring in the first 28 days of study participation: Nonhematologic:
Hematologic:
Toxicities were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 3.0. |
28 days
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Maximum Observed Plasma Concentration of Carfilzomib (Cmax)
Délai: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Time to Maximum Observed Plasma Concentration of Carfilzomib (Tmax)
Délai: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Area Under the Concentration-time Curve to Last Measureable Timepoint (AUClast) for Carfilzomib
Délai: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) for Carfilzomib
Délai: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose.
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Best Clinical Response to Treatment
Délai: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Disease response criteria for NHL were according to the International Working Group Criteria for Non-Hodgkin's Lymphoma. Disease response criteria for Multiple Myeloma were according to the European Group for Blood and Marrow Transplantation (EBMT). Disease response criteria for WM were according to the consensus panel recommendations from the Second International Workshop on Waldenström's Macroglobulinemia. The disease response criteria for Hodgkin's Lymphoma are defined as follows:
Best clinical response is the best response observed from the start of study treatment until disease progression or death. |
From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Duration of Response
Délai: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Duration of objective response is defined as the time from the date of first documented assessment of clinical response (confirmed or unconfirmed complete response, partial response, or minimal response) to the date of documented assessment of progressive disease or death, whichever comes first, plus one day. Participants without tumor progression or death were censored at the date of their last valid clinical response assessment. Median duration of response was calculated using the Kaplan-Meier method. |
From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Time to Progression
Délai: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Time to progressive disease is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease, plus one day. Participants without tumor progression were censored at the date of their last clinical response assessment. Median time to progression was calculated using the Kaplan-Meier method. |
From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Progression-free Survival
Délai: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Progression-free survival is defined as the time from the date of Cycle 1, Day 1 of treatment to the date of documented assessment of progressive disease or death, whichever comes first, plus one day.
Participants without tumor progression or death were censored at the date of their last valid clinical response assessment.
Median progression-free survival was calculated using the Kaplan-Meier method.
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From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase.
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Collaborateurs et enquêteurs
Parrainer
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 (Réel)
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
- Maladies cardiovasculaires
- Maladies vasculaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Maladies lymphatiques
- Troubles immunoprolifératifs
- Tumeurs par site
- Maladies hématologiques
- Troubles hémorragiques
- Troubles hémostatiques
- Paraprotéinémies
- Troubles des protéines sanguines
- Tumeurs, plasmocyte
- Lymphome
- Tumeurs hématologiques
- Myélome multiple
- Maladie de Hodgkin
- Macroglobulinémie de Waldenström
- Effets physiologiques des médicaments
- Agents autonomes
- Agents du système nerveux périphérique
- Agents anti-inflammatoires
- Agents antinéoplasiques
- Antiémétiques
- Agents gastro-intestinaux
- Glucocorticoïdes
- Les hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Agents antinéoplasiques, hormonaux
- Dexaméthasone
Autres numéros d'identification d'étude
- PX-171-002
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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