- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT01279694
Trial of Carfilzomib Plus Melphalan and Prednisone in Elderly Untreated Patients With Multiple Myeloma (CARMYSAP) (CARMYSAP)
Phase I/II Trial of Carfilzomib Plus Melphalan and Prednisone in Elderly Untreated Patients With Multiple Myeloma.
Phase I/II trial of Carfilzomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma. Nine: University Hospital of Nantes, University Hospital of Nancy, University Hospital of Lille, University Hospital of Tours, department Hospital of La Roche Sur Yon, University Hospital of Reims, University Hospital of Clermont-Ferrand, University Hospital of Toulouse, University Hospital of Dijon Newly diagnosed symptomatic Multiple Myeloma > 65 years. Treatment comprises an initial phase consisting of nine 6-week cycles of Carfilzomib on Days 1, 2, 8, 9, 22, 23, 29, 30 (carfilzomib is administered at 20 mg/m2 on Days 1 and 2 of the first cycle and 20, 27, 36 or 45 mg/m2 thereafter) followed by a 12 day rest period (42-day cycle), in combination with oral Melphalan 9 mg/m² and oral prednisone 60mg/m², both on days 1 to 4.
Phase I: Identification of Maximum Tolerated Dose (MTD)
Carfilzomib will be administered at a dose of 20mg/m² for all doses to the first cohort of 6 patients. If dose-limiting toxicities (DLTs) occurred in fewer than 2 of these patients, the next cohort of 6 patients (cohort 2) will receive a dose of 20/27 mg/m² where the 20 mg/m² dose is administered on Day 1 and 2 of Cycle 1 only and then 27 mg/m² for all subsequent doses. If DLTs occurred in fewer than 2 of the patients in cohort 2, the third cohort of 6 patients will receive a dose of 20/36 mg/m² where the 20 mg/m² dose is administered on Day 1 and 2 of Cycle 1 only and then 36 mg/m² for all subsequent doses. If DLTs occurred in fewer than 3 of the patients in cohort 3 the fourth cohort of 6 patients will receive a dose of 20/45 mg/m² where the 20 mg/m² dose is administered on Day 1 and 2 of Cycle 1 only and then 45 mg/m² for all subsequent doses. If at any time during cycle 1 of a dose cohort, ≥ 2 subjects experience a drug-related DLT, the MTD will have been exceeded, additional enrollment within the cohort will cease, and dose escalation will stop. The MTD will be defined as the dose level below which DLT is observed in ≥ 33% (i.e. ≥ 2 of 6) subjects in a cohort. The following are defined as DLTs:
- Any hematologic toxicity of grade 4 intensity or preventing administration of 2 or more of the 8 carfilzomib doses of the first treatment cycle except a) grade 4 thrombocytopenia without bleeding lasting ≤ 7 days or b) grade 4 neutropenia lasting ≤ 7 days
- Grade ≥ 3 febrile neutropenia
- Grade ≥ 3 gastrointestinal toxicities (except for grade ≥ 3 nausea/ vomiting if the patient had not received adequate antiemetic prophylaxis)
- Any other grade ≥ 3 nonhematologic toxicity considered related to CMP by the principal investigator.
- Grade ≥ 3 peripheral neuropathy persisting for more than 3 weeks after discontinuation of study drugs.
Adverse events (AEs) will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). MTD determination will be based on occurrence of DLTs during the first induction treatment cycle only.
Phase II: Expanded Cohort. After identification of the MTD, it is planned for the dose cohort to be expanded to include up to a total of 20 patients treated at the MTD for the phase II part of the study. A full treatment course is the same as for phase I: nine 6-week cycles of CMP.
PRIMARY ENDPOINT Phase I: MTD of combination Phase II: Overall response rate [(ORR), consisting of complete response (CR), very good partial response (VGPR), and partial response (PR) SECONDARY ENDPOINTS Safety and tolerability of CMP Clinical benefit response [(CBR = ORR + minimal response (MR)], Progression-free survival (PFS), Duration of response Overall survival (OS). Safety data analysis will be conducted on all subjects receiving at least one dose of study treatment. Analyses will consist of data summaries for reported AEs. The number and percentage of subjects experiencing one or more AEs will be summarized by dose, relationship to study drugs, and severity. AEs will be coded using MedDRA terminology.
Disease Response Analyses: Overall response rate (ORR = CR + VGPR + PR) to treatment will be measured using the International Myeloma Working Group (IMWG) criteria. Clinical benefit response (CBR = ORR + MR) will be determined using minimal response (at least 6 weeks duration) as defined by the European Group for Blood and Marrow Transplant (EBMT). The distribution of subjects by response category will be made overall and by dose cohort. Time-to-event endpoints will be evaluated with the use of the Kaplan-Meier method and plots will be provided. Analysis of time-to-event outcomes will be performed for the overall sample.
Studieöversikt
Status
Betingelser
Intervention / Behandling
Detaljerad beskrivning
Studietyp
Inskrivning (Faktisk)
Fas
- Fas 2
- Fas 1
Kontakter och platser
Studieorter
-
-
-
Nantes, Frankrike, 44000
- CHU de Nantes
-
-
Deltagandekriterier
Urvalskriterier
Åldrar som är berättigade till studier
Tar emot friska volontärer
Kön som är behöriga för studier
Beskrivning
Inclusion Criteria:
- Karnofsky performance status (KPS) of at least 60%
- Life expectancy of more than 3 months.
- Must understand and voluntarily sign an informed consent form
- Age >65 years at the time of signing consent
- Previously untreated, symptomatic multiple myeloma as defined by the 2 criteria below:○ MM diagnostic criteria (all 3 required):· Monoclonal plasma cells in the bone marrow ≥10% and/or presence of a biopsy-proven plasmacytoma· Monoclonal protein present in the serum and/or urine· Myeloma-related organ dysfunction (at least 1 of the following) [C] Calcium elevation in the blood (serum calcium >10.5 mg/L or upper limit of normal)[R] Renal insufficiency (serum creatinine > 2 mg/dL)[A] Anemia (hemoglobin <10 g/dL or 2 g < normal)[B] Lytic bone lesions or osteoporosisAND have measurable disease by protein electrophoresis analyses as defined by one or more of the following:· IgG multiple myeloma: Serum monoclonal paraprotein (M protein) level by SPEP ³ 0.5 g/dL or urine M-protein level ³ 200 mg/24 hours· IgA multiple myeloma: Serum M-protein level ³ 0.5 mg/dL or urine M-protein level ³ 200 mg/24 hours· IgM multiple myeloma (IgM M-protein plus lytic bone disease documented by skeletal survey plain films): Serum M-protein level ≥ 1.0 g/dL or urine M-protein level ≥ 200 mg/24 hours· IgD multiple myeloma: Serum M-protein level ³ 0.05 g/dL or urine M-protein level ³ 200 mg/24 hours Light chain multiple myeloma: Patients with serum free light chain disease in whom the involved light chain measures ≥ 10 mg/dL
- ECOG performance status of 0, 1, or 2
- Able to adhere to the study visit schedule and other protocol requirements
- Affiliation number to National Health Care System
Exclusion Criteria:
- Patients are ineligible if they meet any of the following criteria: 1 Previous treatment with antimyeloma therapy (does not include radiotherapy, bisphosphonates, or a single short course of steroid [i.e., less than or equal to the equivalent of dexamethasone 40 mg/day for 4 days; such a short course of steroid treatment must not have been given within 28 days (4 weeks) of consent]).
- Any serious medical condition that places the patient at an unacceptable risk if he or she participates in this study.
- Female of childbearing potential
- Any of the following laboratory abnormalities:· Absolute neutrophil count (ANC) < 1,000 cells/mL (1.0 × 109/L) · Platelet count < 50,000 cells/mL (50 × 109/L) for patients in whom < 50% of bone marrow nucleated cells are plasma cells; but platelet count <30,000 cells/mL for patients in whom ³ 50% of bone marrow nucleated cells are plasma cells · Serum SGPT/ALT > 3.0 × upper limit of normal (ULN); Bilirubin >2 × ULN [ALT more specific to liver]· Creatinine clearance ≤ 30 mL/min (Cockcroft-Gault calculation)5 Prior history of malignancies, other than multiple myeloma, unless the subject has been free of the disease for ³ 3 years. Exceptions include the following:o Basal cell carcinoma of the skin Squamous cell carcinoma of the skin Carcinoma in situ of the cervix Carcinoma in situ of the breast6 Incidental histological finding of prostate cancer (TNM stage of T1a or T1b) Peripheral neuropathy of > grade 2 severity.
- Known HIV positivity or active infectious hepatitis, type A, B, or C.
- Myocardial infarction within 3 months of enrollment, unstable angina within 2 months or New York Heart Association class III or IV heart failure.
- Oral or IV fluid hydration contraindicated
Studieplan
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Icke-randomiserad
- Interventionsmodell: Enskild gruppuppgift
- Maskning: Ingen (Open Label)
Vad mäter studien?
Primära resultatmått
Resultatmått |
---|
Phase I: determination of MTD by evaluation of hematological and non hematological toxicity
|
Sekundära resultatmått
Resultatmått |
---|
Safety of CMP Clinical benefit response [(CBR = ORR + minimal response (MR)], Progression-free survival (PFS), Duration of response Overall survival (OS).
|
Tolerability of CMP Clinical benefit response [(CBR = ORR + minimal response (MR)], Progression-free survival (PFS), Duration of response Overall survival (OS).
|
Samarbetspartners och utredare
Sponsor
Utredare
- Huvudutredare: Philippe Moreau, CHU Nantes
- Huvudutredare: Denis Caillot, CH DIJON
- Huvudutredare: Thierry FACON, CHRU - Hôpital Claude Huriez Lille
- Huvudutredare: Cyril Hulin, Hôpital de Brabois Nancy
- Huvudutredare: Brigitte Kolb, Hôpital R. Debré Reims
- Huvudutredare: Hervé Maisonneuve, CHD La Roche sur Yon
- Huvudutredare: Michel Attal, CHRU - Hôpital Purpan Toulouse
- Huvudutredare: Benboubker, CHRU - Hôpital Bretonneau Tours
Publikationer och användbara länkar
Studieavstämningsdatum
Studera stora datum
Studiestart
Primärt slutförande (Faktisk)
Avslutad studie (Faktisk)
Studieregistreringsdatum
Först inskickad
Först inskickad som uppfyllde QC-kriterierna
Första postat (Uppskatta)
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
Senast verifierad
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Hjärt-kärlsjukdomar
- Kärlsjukdomar
- Immunsystemets sjukdomar
- Neoplasmer efter histologisk typ
- Neoplasmer
- Lymfoproliferativa störningar
- Immunproliferativa störningar
- Hematologiska sjukdomar
- Hemorragiska störningar
- Hemostatiska störningar
- Paraproteinemier
- Blodproteinstörningar
- Multipelt myelom
- Neoplasmer, Plasmacell
- Läkemedels fysiologiska effekter
- Molekylära mekanismer för farmakologisk verkan
- Antiinflammatoriska medel
- Antineoplastiska medel
- Immunsuppressiva medel
- Immunologiska faktorer
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitut och hormonantagonister
- Antineoplastiska medel, hormonella
- Antineoplastiska medel, Alkylering
- Alkyleringsmedel
- Myeloablativa agonister
- Prednison
- Melphalan
Andra studie-ID-nummer
- 10/3-D
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Myelom
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University och andra samarbetspartnersAktiv, inte rekryterandeMultipelt myelom vid återfall | Multipelt myelom med misslyckad remission | Multipelt myelom stadium I | Multipelt myelomprogression | Multipelt myelom steg II | Multipelt myelom steg IIIKanada
-
University of WashingtonNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Barbara Ann Karmanos Cancer InstituteNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
National Cancer Institute (NCI)AvslutadVorinostat och Bortezomib vid behandling av patienter med återfall eller refraktärt multipelt myelomSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
Mayo ClinicAvslutadMultipelt myelom | Steg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
National Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
-
National Cancer Institute (NCI)AvslutadSteg I multipelt myelom | Steg II multipelt myelom | Steg III multipelt myelom | Refraktärt multipelt myelomFörenta staterna
Kliniska prövningar på Carfilzomib
-
Ajai ChariAmgenAvslutadRefraktärt multipelt myelom | Återfall av multipelt myelomFörenta staterna
-
M.D. Anderson Cancer CenterOnyx Therapeutics, Inc.AvslutadLymfomFörenta staterna
-
Thomas LundRekrytering
-
University of ArkansasOnyx Therapeutics, Inc.Inte längre tillgänglig
-
AmgenMultiple Myeloma Research FoundationGodkänd för marknadsföring
-
AmgenAvslutadNjursjukdom i slutskedet | Återfall av multipelt myelomFörenta staterna, Australien, Kanada
-
Washington University School of MedicineAvslutadLeukemiFörenta staterna
-
NovartisAmgenAvslutad
-
SCRI Development Innovations, LLCAmgenAvslutadNeuroendokrin cancerFörenta staterna
-
John F. McDyer, MDAvslutadKombinationsterapi med karfilzomib för antikroppsmedierad avstötningsdiagnos vid lungtransplantationAvstötning av lungtransplantationFörenta staterna