- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT01711671
A Study of DKN-01 and Lenalidomide/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
A Pilot Study of DKN-01 and Lenalidomide (Revlimid®)/Dexamethasone Versus Lenalidomide/Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
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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Georgia
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Atlanta, Georgia, États-Unis, 30322
- Emory University Hospital
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Massachusetts
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Boston, Massachusetts, États-Unis, 02115
- Dana-Farber Cancer Institute
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Boston, Massachusetts, États-Unis, 02114
- Massachusetts General Hospital
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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:
Relapsed or refractory Multiple Myeloma (MM)
a. Treated with at least 1 prior regimen for myeloma
- Prior treatment with bortezomib (Velcade) is acceptable with a wash-out of 2 weeks
- Treatment with prior autologous transplant is permitted
- If a transplant is used as consolidation following chemotherapy, without intervening disease progression, it will be considered 1 line of treatment with the preceding chemotherapy
Diagnosis of symptomatic MM as defined by the International Myeloma Working Group (IMWG) :
- Second line or greater/Refractory/Relapsed, Stage I, Stage II, Stage III
- Measureable disease as indicated by monoclonal protein in the serum of greater than or equal to (≥) 1 grams per deciliter (g/dL), involved serum free light chain assay ≥10 mg/dL (≥100 mg/L) provided the serum free light chain ratio is abnormal; monoclonal light chain in the urine protein electrophoresis of ≥ 200 mg/24 hours, or measurable plasmacytoma
- At least 1 osteolytic bone lesion
- Disease-free of active second/secondary or prior malignancies for equal to or over 5 years with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the cervix or breast
- Ambulatory patients greater than or equal to (≥) 30 years of age
- Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
- Estimated life expectancy of ≥ 26 weeks
Adequate organ function including:
Hematologic:
- Absolute neutrophil count (ANC) greater than or equal to (≥) 1000/microliter
- Platelet (PLT) count ≥ 75,000/microliter
- Hemoglobin (Hgb) ≥ 8.0 g/dL
Acceptable coagulation status:
- Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.2 x the upper limit of normal (ULN) unless receiving anticoagulation therapy. If receiving anticoagulation therapy, eligibility will be based upon International Normalization Ratio (INR)
International normalized ratio (INR) less than or equal to (≤) 1.6 (unless receiving anticoagulation therapy)
- If receiving warfarin: INR ≤ 3.0 (and no active bleeding, [i.e., no bleeding within 14 days prior to first dose of study therapy])
Hepatic:
- Bilirubin ≤ 1.5 x ULN
- Alanine Transaminase (ALT) and Aspartate Transaminase (AST) ≤ 2.5 x ULN (if liver metastases are present, then ≤ 5 x ULN is allowed)
Renal:
- Calculated creatinine clearance ≥ 45 mL using the Cockcroft and Gault Method
Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 10 to 14 days and again within 24 hours of starting study drug
- WCBP must agree to have pregnancy tests monthly (every 14 days for women with irregular cycles) while on study drug and 4 weeks after the last dose of study drug
- Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy
- Males and females with reproductive potential must agree to use medically approved contraceptive precautions starting 4 weeks prior to initiation of the therapy and during the trial and for 18 months following the last dose of study drug
- Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Provide written informed consent prior to any study-specific procedures
- Are reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures
Exclusion Criteria:
- Received treatment with an investigational drug, which has not received regulatory approval for any indication, within 28 days of study treatment with DKN-01
- Received any experimental non-drug therapy (e.g., donor leukocyte/mononuclear cell infusions) within 56 days of entry
- Previously treated with an anti-Dickkopf-1 (anti-DKK-1) or antibody therapy, or have had a significant allergy to a known pharmaceutical therapy that, in the opinion of the Investigator, poses an increased risk to the patient
- Received radiation therapy, surgery, or chemotherapy within 2 weeks prior to study entry (6 weeks for nitrosoureas or Mitomycin C)
- Received bisphosphonates (e.g., etidronate, clodronate, tiludronate, pamidronate, neridronate, olpadronate, alendronate, ibandronate, risedronate, zoledronate) within 2 weeks prior to study entry
- Symptomatic central nervous system (CNS) malignancy or metastasis. Patients with treated CNS metastases are eligible provided their disease is radiographically stable, asymptomatic, and they are not currently receiving corticosteroids and/or anticonvulsants. Screening of asymptomatic patients without a history of CNS metastases is not required
- Have a history of major organ transplant (for example: heart, lungs, liver, and kidney)
- Are pregnant or nursing
- Known to be human immunodeficiency virus (HIV) positive, have hepatitis B surface antigen (HBSAg), or hepatitis C antibodies (HCAb)
- Active, uncontrolled bacterial, viral, or fungal infections, including urinary tract infection, within 7 days of study entry requiring systemic therapy
- Serious cardiac condition such as myocardial infarction within the past 6 months, unstable angina, or Class III or IV congestive heart failure as defined by the New York Heart Association (NYHA); have ECG abnormalities including baseline 12-lead ECG with Fridericia-corrected QT interval (QTcF) > 470 msec (female) or > 450 msec (male), a history of congenital long QT syndrome, or any ECG abnormality that, in the opinion of the Investigator, would preclude safe participation in the study
- History of osteonecrosis of the hip or have evidence of structural bone abnormalities in the proximal femur on MRI scan that are considered clinically significant or may have an impact on the interpretation of the scan. Degenerative changes of the hip joint are not exclusionary
- Known concomitant disease(s) known to influence calcium metabolism including hyperparathyroidism, hyperthyroidism, Paget's disease of bone, or any other concurrent severe or uncontrolled concomitant medical condition that, in the opinion of the Investigator, would preclude participation in this study
- Patients who are currently receiving lithium chloride (LiCl)
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 |
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Expérimental: DKN-01 300mg
DKN-01 plus lenalidomide (Revlimid)/dexamethasone
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300 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone
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Expérimental: DKN-01 600mg
DKN-01 plus lenalidomide (Revlimid)/dexamethasone
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600 mg IV infusion of DKN-01 administered twice per 28 day cycle on Days 1 and 15, plus lenalidomide/dexamethasone
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Comparateur actif: Standard of Care
Lenalidomide (Revlimid)/dexamethasone
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Current approved standard of care
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) standard uptake value (SUV)
Délai: Pre-study to after 6 months of therapy
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SUV as measured by NaF-PET/CT in both myeloma bone lesions and normal bone
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Pre-study to after 6 months of therapy
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Fluorine F18 sodium fluoride positron emission tomography (NaF-PET/CT) influx constant (Ki)
Délai: Pre-study to after 6 months of therapy
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Ki as measured by NaF-PET/CT in both myeloma bone lesions and normal bone
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Pre-study to after 6 months of therapy
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F18 fluorodeoxyglucose positron emission tomography (FDG-PET/CT) standard uptake value (SUV)
Délai: Pre-study to after 6 months of therapy
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SUV as measured by FDG-PET/CT in both myeloma bone lesions and normal bone
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Pre-study to after 6 months of therapy
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Number of patients with treatment emergent adverse events
Délai: Baseline to study completion (approximately 7 months)
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Baseline to study completion (approximately 7 months)
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Mesures de résultats secondaires
Mesure des résultats |
Délai |
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Overall response rate (ORR)
Délai: Baseline to study completion (approximately 7 months)
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Baseline to study completion (approximately 7 months)
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Progression free survival (PFS)
Délai: Baseline to study completion (approximately 7 months)
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Baseline to study completion (approximately 7 months)
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Duration of response
Délai: Baseline to study completion (approximately 7 months)
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Baseline to study completion (approximately 7 months)
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Overall survival
Délai: Baseline to study completion (approximately 7 months)
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Baseline to study completion (approximately 7 months)
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Pharmacokinetics: area under the concentration - time curve (AUC) of a single dose of DKN-01
Délai: Dosing interval of 2 weeks following the first dose in Cycle 1
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Dosing interval of 2 weeks following the first dose in Cycle 1
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Pharmacokinetics: maximum plasma concentration (Cmax) of a single dose of DKN-01
Délai: Dosing interval of 2 weeks following the first dose in Cycle 1
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Dosing interval of 2 weeks following the first dose in Cycle 1
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Pharmacokinetics: trough DKN-01 concentrations on Cycle 2 and Cycle 3
Délai: Cycle 2 Day 1 Pre-dose, Cycle 3 Day 1 Pre-dose
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Cycle 2 Day 1 Pre-dose, Cycle 3 Day 1 Pre-dose
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Paul Whitlock, Theorem Clinical Research
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
Termes MeSH pertinents supplémentaires
- Maladies cardiovasculaires
- Maladies vasculaires
- Maladies du système immunitaire
- Tumeurs par type histologique
- Tumeurs
- Troubles lymphoprolifératifs
- Troubles immunoprolifératifs
- Maladies hématologiques
- Troubles hémorragiques
- Troubles hémostatiques
- Paraprotéinémies
- Troubles des protéines sanguines
- Myélome multiple
- Tumeurs, plasmocyte
- Effets physiologiques des médicaments
- Agents autonomes
- Agents du système nerveux périphérique
- Agents anti-inflammatoires
- Agents antinéoplasiques
- Facteurs immunologiques
- Antiémétiques
- Agents gastro-intestinaux
- Glucocorticoïdes
- Les hormones
- Hormones, substituts hormonaux et antagonistes hormonaux
- Agents antinéoplasiques, hormonaux
- Inhibiteurs de l'angiogenèse
- Agents modulateurs de l'angiogenèse
- Substances de croissance
- Inhibiteurs de croissance
- Dexaméthasone
- Lénalidomide
Autres numéros d'identification d'étude
- DEK-DKK1-P101
- DKN-01
- LY2812176 (Healthcare Pharmaceuticals)
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
produit fabriqué et exporté des États-Unis.
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 DKN-01 300 mg
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Johannes Gutenberg University MainzLeap Therapeutics, Inc.Inconnue
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