NCT03520985

Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma

Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma. A Multi-center, Single Arm Phase II Trial

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 34 (actual)
• Sponsor: Swiss Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Pomalidomide is an approved treatment for refractory multiple myeloma. Toxicity of pomalidomide in the pivotal MM-003 trial, was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. This resulted in frequent dose interruptions (67%) and dose reductions (27%). This suggests that for the majority of patients the 4 mg daily dosing schedule is too toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance. The aim of this trial therefore is to establish that alternate day dosing of pomalidomide (4 mg q2d, d1-28) is non-inferior to daily dosing (4 mg d1-21 q28) in terms of efficacy of the drug with potentially less side effects.

Detailed description

Multiple myeloma (MM) accounts for 1% of all cancers and ∼10% of all hematological malignancies. Despite recent advances in myeloma treatment, including the introduction of proteasome inhibitors, immunomodulatory drugs (IMiDs) and stem cell transplantation, myeloma remains an incurable disease. The treatment of bortezomib and lenalidomide refractory myeloma is still an unmet medical need. Once patients have relapsed after IMiD-containing therapies and have become bortezomib-resistant, their prognosis is extremely poor. Pomalidomide is a third-generation, Swissmedic approved, oral immunomodulatory drug with activity in such patients. However the toxicity of pomalidomide in the pivotal MM-003 trial was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. This resulted in frequent dose interruptions (67%) and dose reductions (27%). This suggests that for the majority of patients the 4 mg daily dosing schedule (4 mg daily on 21 of 28 days) is toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance. Alternative dosing schedules: There is robust data available indicating that lower pomalidomide doses (e.g. 2 mg daily) lead to similar responses and progression free survival with fewer side effects. Due to its unique pharmacological characteristics, pomalidomide is well suited for alternate day dosing. The decline of the plasma concentration at the terminal phase is slow. These data make pomalidomide an ideal candidate for alternate day dosing. Therefore, a phase I study has already been conducted in 2008 to test the alternating administration of the drug showing excellent responses with a marked reduction of thrombotic events and less severe myelosuppression. The drug costs of pomalidomide are quite high. Interestingly, the manufacturer determined a pricing model that is independent from the capsule strength (costs for one capsule 1 mg=2 mg=3 mg=4 mg). In patients requiring dose reductions due to hematologic toxicity, daily dosing of reduced strength pomalidomide (e.g. 2 mg daily) is approved and suggested by the manufacturer. This delivers 50% less pomalidomide to the patient, albeit at 100% of the price of full dosing. In summary, the establishment of the modified pomalidomide schedule would be an interesting option for our patients to achieve similar efficacy with fewer side effects. In addition, it would optimize the cost-effectiveness of the drug.

Conditions

• Refractory Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Pomalidomide	Pomalidomide (4 mg p.o.) will be administered on every other day of each 28-day treatment cycle. Treatment duration: Treatment cycles are repeated until confirmed disease progression.
DRUG	Dexamethasone	For patients ≤ 75 years of age: Low-Dose Dexamethasone (40 mg p.o.) will be administered once per day on days 1, 7, 15, and 21 of a 28-day cycle. For patients \> 75 years of age: Low-Dose Dexamethasone (20 mg p.o.) will be administered once per day on days 1, 7, 15, and 21 of a 28-day cycle. Treatment duration: Treatment cycles are repeated until confirmed disease progression.

Timeline

• Start date: 2018-10-01
• Primary completion: 2021-02-03
• Completion: 2021-02-03
• First posted: 2018-05-11
• Last updated: 2021-06-10

Locations

16 sites across 1 country: Switzerland