Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments carfilzomib, pomalidomide, dexamethasone
Phase phase 1/phase 2
Target proteasome
Sponsor Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborator University of Turin, Italy
Start date June 2014
End date July 2015
Trial size 57 participants
Trial identifier NCT02185820, EMN07/IST-CAR-538

Summary

This protocol is a phase I/II multicenter study designed to assess the safety and the efficacy of the proposed combinations in relapsed and/or refractory Multiple Myeloma (MM) patients.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Treatment schedule for 8 cycles of induction: Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 27/36/45/56 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 27/36/45/56 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28). Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days. Treatment schedule for maintenance until progression or intolerance: Carfilzomib = at the MTD achieved in the phase I of the study on days 1, 8, 15 in 28-days cycles. Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22.
carfilzomib
pomalidomide
dexamethasone

Primary Outcomes

Measure
DLT
time frame: 1 year
Partial response
time frame: 3 years

Secondary Outcomes

Measure
Toxicities
time frame: 3 years
PFS
time frame: 3 years
TTP
time frame: 3 years
DFS
time frame: 3 years
DOR
time frame: 3 years
TTNT
time frame: 3 years
OS
time frame: 3 years
Tumor response and survival
time frame: 3 years

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria

    Exclusion Criteria

      Additional Information

      Official title A MULTICENTER, OPEN LABEL PHASE I/II STUDY OF CARFILZOMIB, POMALIDOMIDE AND DEXAMETHASONE IN RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (MM) PATIENTS
      Principal investigator Antonio Palumbo, MD
      Description TREATMENT PERIOD Patients will start the salvage treatment with CPd, as soon as the screening visits of the pre-treatment period have been terminated. Patients will receive 8 CPd cycles. PHASE I In the phase I part of the study, the following dose levels of pomalidomide will be studied with a constant dose of dexamethasone and carfilzomib: Level -1 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 27 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 27 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28). Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days. Level 0 (starting dose) Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 36 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 36 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28). Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days. Level +1 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 45 mg/ m2 days 8, 15 in cycle 1, then for all subsequent doses 45 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28). Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days. Level +2 Carfilzomib = 20 mg/m2 IV once daily on days 1 of cycle 1 only followed by 56 mg/m2 days 8, 15 in cycle 1, then for all subsequent doses 56 mg/m2 IV once daily on days 1, 8, 15 followed by 13-day rest period (day 16 through 28). Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22 every 28 days. Patients will be observed during the first 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 none of the 3 experience DLT, dose escalation will continue. If one of three patients experience DLT, three additional patients will be added to this cohort (max 6). If two of three patients experience a DLT at any given dose, the MTD will have been exceeded and the MTD will be the preceding dose at which < one of 6 patients experienced a DLT. If no further patients experience DLT (1 of 6) dose escalation will continue. If 2 patients experience DLT (2 of 6) the MTD will have been exceeded and the MTD will be the previous dose at which <1 patient of 6 experienced DLT. The phase I of the study will end once the MTD has been defined. PHASE II The phase II of the study will start after the MTD has been defined in the phase I of the study. The dose used to treat patients in the phase II will be the MTD defined in the phase I of the study. In the second part of the study, the MTD of the association CPd (or in absence of any MTD observed) the doses of dose level 3 (maximum per protocol dose) will be administered to a total of 45 consecutive patients in order to assess response rate and clinical efficacy. THE PHASE 2 OF THE STUDY WILL START ONLY AFTER THE ANALYSIS OF THE PHASE 1 RESULTS AND THE RELEVANT STUDY REPORT. MANTEINANCE PERIOD At the end of 8 courses, maintenance phase will start. Patients will receive: Carfilzomib = at the MTD achieved in the phase I of the study on days 1, 8, 15 in 28-days cycles. Pomalidomide = 4 mg daily on days 1 - 21 every 28 days. Dexamethasone = 20 mg on days 1, 8, 15, 22. Patients will be stopped at PD or intolerance. For the maintenance period a continuous assessment of the toxicity and tolerability profile of the CPd combination could permit to the Investigators to continue the treatment using Pomalidomide or Carfilzomib alone according to the dose modification plan.
      Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
      Information provided to ClinicalTrials.gov by Stichting Hemato-Oncologie voor Volwassenen Nederland.