NCT02294357

Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib

A Phase 2 Study of Weekly 70 mg/m2 Carfilzomib for Multiple Myeloma Patients Refractory to 27 mg/m2 Carfilzomib

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Oncotherapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this Phase II study is to evaluate the safety and effectiveness (good and bad effects) of carfilzomib given as a 30-minute infusion and at a dose of 70 mg/m2 to treat patients with multiple myeloma (MM), who are currently showing progressive disease (worsening) and had progressed (did not respond to treatment) within 8 weeks of receiving treatment with twice weekly 27mg/m2 of carfilzomib. Carfilzomib is approved by the U.S. Food and Drug Administration (FDA) to be used only in certain U.S. patients with relapsed and refractory multiple myeloma that have tried and failed other therapies. Carfilzomib is considered an investigational drug for this study because the dose and regimen included in this study are different from the FDA approved carfilzomib regimen. Carfilzomib is a type of drug called a proteasome inhibitor. Carfilzomib is thought to work by preventing breakdown of abnormal proteins in cells, causing the cells to die. Cancer cells are more sensitive to these effects than normal cells. Carfilzomib has been previously given to more than 1800 people in clinical trials.

Detailed description

This is a Phase 2, multicenter, open label, non-randomized study to evaluate the safety and efficacy of a 30-minute infusion of 70 mg/m2 of carfilzomib among MM patients who are currently showing progressive disease (PD) and had failed their last treatment with twice weekly 27mg/m2 of carfilzomib alone or as part of a combination regimen. The study will consist of 1) a screening period; 2) up to eight 28-day, treatment cycles; 3) maintenance treatment; 4) a final assessment to occur 28 days after the end of the last treatment cycle; and 5) a follow-up period. The study will enroll a total of 45 patients who are currently showing PD and had progressed within 8 weeks of receiving their last treatment with twice weekly 27mg/m2 of carfilzomib alone or as part of a combination regimen. Additionally, patients who have not achieved a complete response (CR) and have plateaued (as defined by unchanged disease markers for at least 8 weeks) while treated with a combination of carfilzomib (twice weekly 27 mg/m2), lenalidomide and dexamethasone; carfilzomib (twice weekly 27 mg/m2), pomalidomide and dexamethasone; or carfilzomib (twice weekly 27 mg/m2) and dexamethasone are also eligible for this study. Patients who were treated with a carfilzomib (twice weekly 27 mg/m2) containing combination who are currently on carfilzomib (twice weekly 27 mg/m2) and dexamethasone with or without lenalidomide or pomalidomide maintenance therapy and are not in CR and show unchanged disease markers for at least 8 weeks will also be eligible. Patients will be enrolled from 15 hematology/oncology sites across the United States. During the treatment period, all doses of carfilzomib will be given at 70 mg/m2 infused over 30 minutes. Among patients who received steroids at the equivalent of \> 8 mg of dexamethasone weekly with carfilzomib, steroids will be administered using the same drug(s) at the same dose(s) and schedule(s) as they received during their previous carfilzomib treatment. Patients who did not receive steroids or received the equivalent of less than 8 mg of dexamethasone weekly will be given 8 mg of dexamethasone prior to each carfilzomib administration. Carfilzomib will be administered at a facility capable of managing hypersensitivity reactions. Pre- and post-dose intravenous (IV) hydration (between 250 mL and 500 mL normal saline or other appropriate IV fluid formulation) may be given at the discretion of the treating physician. Subjects should be monitored periodically during this period for evidence of fluid overload. Subjects who complete 8 cycles without showing PD will be eligible to receive maintenance therapy on a 28-day cycle with carfilzomib and steroids as administered during the last cycle of the treatment period. In addition, those treated with lenalidomide with carfilzomib and dexamethasone will continue lenalidomide at the same dose and schedule as used during the treatment period. For those treated with pomalidomide with carfilzomib and dexamethasone, pomalidomide will be administered at the same dose and schedule as during treatment. During maintenance (cycle 9 and beyond), carfilzomib will be administered at the dose received during the last cycle of study treatment on Days 1, 8 and 15, and steroids will be administered using the same drug(s) at the same dose(s) and schedule(s) as given during the last cycle of study treatment. Patients will remain on maintenance therapy until documentation of PD as defined by the modified Bladé criteria or until they develop toxicity. Patients with stable disease (SD) will remain on maintenance therapy. Dose reductions of carfilzomib and steroids will be permitted as per protocol guidelines.

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Carfilzomib
DRUG	Dexamethasone	If the patient was receiving steroids at the equivalent of \> 8 mg of dexamethasone weekly either intravenously (IV) or Per Orem (PO) in combination with carfilzomib, the same drug(s), dose(s) and schedule(s) of steroids will be continued. If the patient was not receiving steroids or was receiving less than the equivalent of 8 mg of dexamethasone weekly, then he/she will be given 8 mg of dexamethasone (IV or PO) prior to each carfilzomib administration.
DRUG	Prednisone	f the patient was receiving prednisone, at the equivalent of \> 8 mg of dexamethasone weekly PO in combination with carfilzomib, he/she will continue to receive prednisone at the same dose and schedule.
DRUG	Methylprednisolone	If the patient was receiving methylprednisolone at the equivalent of \> 8 mg of dexamethasone weekly either IV or PO in combination with carfilzomib, he/she will continue to receive methylprednisolone at the same dose and schedule.
DRUG	Lenalidomide	given at same dose and schedule as patient was receiving while being treated with twice weekly carfilzomib at 27 mg/m2
DRUG	Pomalidomide	administered PO at 4mg daily on days 1-21 of a 28 day cycle

Timeline

• Start date: 2014-12-01
• Primary completion: 2020-09-21
• Completion: 2020-09-22
• First posted: 2014-11-19
• Last updated: 2023-11-01

Locations

7 sites across 1 country: United States