NCT02204241

Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Patients

A Multicenter, Open Label Phase I/II Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma (MM) Patients

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: European Myeloma Network B.V. · Network
• Sex: All
• Age: 65 Years
• Healthy volunteers: Not accepted

Summary

This protocol is a phase I/II multicenter study designed to assess the safety and the efficacy of the proposed combinations as up-front treatment in elderly Multiple Myeloma (MM) patients.

Detailed description

Treatment schedule for 9 cycles of induction: Phase I: In the phase I portion of the study, the following dose levels of carfilzomib will be studied with fixed doses of dexamethasone and cyclophosphamide to define the maximum tolerated dose (MTD): Level-1: 1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 36 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 36 mg/m2 IV once daily on days 1-2, 8-9, 15-16. 2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15 3. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9, 15-16, 22-23 Level 0: 1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 45 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 45 mg/m2 IV once daily on days 1-2, 8-9, 15-16. 2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15 3. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9, 15-16, 22-23 Level +1: 1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 56 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 56 mg/m2 IV once daily on days 1-2, 8-9, 15-16. 2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15 3. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9, 15-16, 22-23 Level +2: 1. Carfilzomib given 20 mg/m2 IV once daily on days 1-2 of Cycle 1 only followed by 36 mg/m2 on days 8-9, 15-16, of Cycle 1, then for all subsequent doses 70 mg/m2 IV once daily on days 1-2, 8-9, 15-16. 2. Cyclophosphamide given orally at the dose of 300 mg/m2 on days 1, 8, 15 3. Dexamethasone given orally at the dose of 40 mg on days 1, 8, 15, 22 or 20 mg on days 1-2, 8-9, 15-16, 22-23 Patient will be observed at the end of the second cycle of therapy for the assessment of side effects and observation of DLTs. Dose escalation will proceed as follows: * 3 patients will be entered at dose level 0 * If 0/3 patients experience DLT, dose escalation will continue * If 1/3 patients experience DLT, 3 additional patients will be added to this cohort (max 6) * If no further patients experience DLT (1/6) dose escalation will continue * If 2/6 patients experience DLT, the MTD will have been exceeded and the MTD will be the previous dose at which \<2/6 experienced DLT * If 2/3 patients experience a DLT at any given dose, the MTD will have been exceeded and the MTD will be the preceding dose at which \< 2/6 (or 1/3) patients experienced a DLT. Phase II: The dose used to treat patients in the phase II will be the MTD defined in the phase I of the study. Treatment schedule for maintenance until progression or intolerance: Carfilzomib at the MTD defined by phase I study IV once daily on days 1-2, 15-16.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Carfilzomib
DRUG	Cyclophosphamide
DRUG	Dexamethasone

Timeline

• Start date: 2014-06-01
• Primary completion: 2015-06-01
• Completion: 2023-04-01
• First posted: 2014-07-30
• Last updated: 2023-07-03

Locations

1 site across 1 country: Italy