NCT03143049

Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma

Randomized Phase 3 Study of Pomalidomide-Cyclophosphamide-Dexamethasone (PCD) Versus Pomalidomide-Dexamethasone (PD) in Relapse or Refractory Myeloma. An AMN Study

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 120 (estimated)
• Sponsor: National University Hospital, Singapore · Academic / Other
• Sex: All
• Age: 21 Years – 99 Years
• Healthy volunteers: Not accepted

Summary

Myeloma patients who relapse after prior treatment with bortezomib and lenalidomide have survival of less than 1 year. Recently, a randomized study of Pomalidomide and dexamethasone conducted in compared with placebo and dexamethasone showed that pomalidomide can improve survival of this group of patients. As a result, pomalidomide is now approved by the FDA and EMA for use in patients with relapsed/refractory myeloma previously treated with bortezomib and lenalidomide. We have conducted a study using Pomalidomide plus Dexamethasone (PD) in Asian patients, which showed good efficacy and safety profile. More important for patients with suboptimal response to PD will achieve a clinically meaningful response with the addition of oral cyclophosphamide (PCD). In the United States, a small randomised phase 2 study of PCD versus PD showed that PCD have a higher response rates, produce deeper response and correspondingly longer progression free survival. There is till date no randomised phase 3 study between these regimens. This will be important to determine what is the best combination including pomalidomide for use in relapse myeloma.

Detailed description

In this study, we will prospectively enrol 120 Asian patients with relapsed myeloma after prior treatment with bortezomib and lenalidomide, and randomised them between PCD and PD (60 in each arms). Centers in Singapore, Korea, Taiwan, and Hong Kong will participate in this study. Pomalidomide is a new immunomodulatory drug, which has been shown to be active in myeloma patients who relapse after bortezomib and lenalidomide. A recent phase III study comparing pomalidomide plus dexamethasone with placebo plus high dose dexamethasone in patients with prior exposure to bortezomib and lenalidomide, showed that the use of pomalidomide significantly improve the overall survival of these patients. In an Asian study, it appears that the addition of cyclophosphamide can induce further response in patients without a response to PD. In the United States, a small randomised phase 2 study of PCD versus PD showed that PCD have a higher response rates, produce deeper response and correspondingly longer progression free survival. Our hypothesis is therefore that PCD will be better than PD and should be the standard pomalidomide containing regimen for relapse myeloma patients. This combination will also be highly relevant to Asian patients because cyclophosphamide is a relatively cheap drug and the combination will be cost effective if proven to be better than PD. Rationale for the Study Purpose There is a relative lack of data on the efficacy and tolerability of PCD in Asian Patients. The current study will also allow us to test if PCD is better than PD in the treatment of relapse myeloma patients. Rationale for Study Population The study population will be myeloma patients who have relapsed following prior treatment with bortezomib and lenalidomide. Pomalidomide is the current approved treatment choice for this group of patients and a common indication for us in Asia.

Conditions

• Relapse Multiple Myeloma

Interventions

Type	Name	Description
DRUG	PCD	For PCD, patients will be treated as follows: PO pomalidomide 4mg from D1-21, PO cyclophosphamide 400mg on D1, 8 and 15, and PO or IV dexamethasone 40mg D1, 8, 15 and 22 in a 28-day cycle. Patients will be assessed every 28 days (+/- 10 days). Patients shall receive the treatment until disease progression, unacceptable toxicity as determined by treating physician, withdrawal of consent or mortality (whichever occurs first).
DRUG	PD	For PD, Patients will be treated as follows: PO pomalidomide 4mg from D1-21 and PO or IV dexamethasone 40mg D1, 8, 15 and 22 in a 28-day cycle. Patients will be assessed every 28 days (+/- 10 days). Patients shall receive the treatment until disease progression, unacceptable toxicity as determined by treating physician, withdrawal of consent or mortality (whichever occurs first).

Timeline

• Start date: 2017-09-13
• Primary completion: 2018-06-01
• Completion: 2022-06-01
• First posted: 2017-05-08
• Last updated: 2017-11-06

Locations

5 sites across 5 countries: Hong Kong, Japan, Singapore, South Korea, Taiwan