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

Multiple Myeloma Clinical Trial

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

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

• NCT number: NCT02204241
• Study type: Interventional
• Source: European Myeloma Network
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2014
• Completion date: April 2023