Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma
- Conditions
- Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT03520985
- Lead Sponsor
- Swiss Group for Clinical Cancer Research
- Brief 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 34
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Pomalidomide Pomalidomide The treatment in this trial consists of oral pomalidomide on alternate days (ad) plus Low-Dose Dexamethasone (adPOM + LD-DEX) Pomalidomide Dexamethasone The treatment in this trial consists of oral pomalidomide on alternate days (ad) plus Low-Dose Dexamethasone (adPOM + LD-DEX)
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months OR is defined as minimal response or better, assessed according to the IMWG criteria.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) at 12 months at 12 months OS, as defined above, will be evaluated at 12 months.
Overall Survival (OS) From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months OS is defined as the time from registration until death from any cause. Patients not having an event at the time of analysis will be censored at the date they were last known to be alive.
Progression-free survival (PFS) From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months PFS is defined as the time from registration until progression according the IMWG criteria or death from any cause, whichever occurs first. Patients not having an event at the time of analysis as well as patients starting a new anticancer therapy in the absence of an event will be censored at the date of their last tumor assessment showing non-progression before starting a new treatment, if any.
Trial Locations
- Locations (16)
Onkozentrum Hirslanden Zürich
🇨🇭Zurich, Switzerland
OnkoZentrum Zürich AG - Klinik im Park
🇨🇭Zürich, Switzerland
Kantonspital Aarau
🇨🇭Aarau, Switzerland
Kantonsspital Baden (Baden/Brugg)
🇨🇭Baden, Switzerland
Inselspital Bern
🇨🇭Bern, Switzerland
Kantonsspital Luzern
🇨🇭Luzerne, Switzerland
Kantonsspital St. Gallen
🇨🇭St. Gallen, Switzerland
Kantonsspital Liestal
🇨🇭Liestal, Switzerland
Universitätsspital Zürich
🇨🇭Zürich, Switzerland
Universitätsspital Basel
🇨🇭Basel, Switzerland
Istituto Oncologico Svizzera Italiana IOSI
🇨🇭Bellinzona, Switzerland
Regionalspital Thun
🇨🇭Thun, Switzerland
Kantonsspital Winterthur
🇨🇭Winterthur, Switzerland
Kantonsspital Graubünden
🇨🇭Chur, Switzerland
Hopital Fribourgeois HFR
🇨🇭Fribourg, Switzerland
Spital Thurgau AG
🇨🇭Münsterlingen, Switzerland