Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma (OptiPOM)
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|ClinicalTrials.gov Identifier: NCT03520985|
Recruitment Status : Active, not recruiting
First Posted : May 11, 2018
Last Update Posted : January 13, 2021
|Condition or disease||Intervention/treatment||Phase|
|Refractory Multiple Myeloma||Drug: Pomalidomide Drug: Dexamethasone||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||75 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma. A Multi-center, Single Arm Phase II Trial|
|Actual Study Start Date :||October 1, 2018|
|Estimated Primary Completion Date :||March 2023|
|Estimated Study Completion Date :||December 2025|
The treatment in this trial consists of oral pomalidomide on alternate days (ad) plus Low-Dose Dexamethasone (adPOM + LD-DEX)
Pomalidomide (4 mg p.o.) will be administered on every other day of each 28-day treatment cycle.
Treatment cycles are repeated until confirmed disease progression.
Other Name: Imnovid®
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 cycles are repeated until confirmed disease progression.
- Overall Response Rate (ORR) [ Time Frame: 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.
- Overall Survival (OS) [ Time Frame: 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.
- Overall Survival (OS) at 12 months [ Time Frame: at 12 months ]OS, as defined above, will be evaluated at 12 months.
- Progression-free survival (PFS) [ Time Frame: 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520985
|Aarau, Switzerland, CH-5001|
|Kantonsspital Baden (Baden/Brugg)|
|Baden, Switzerland, 5404|
|Basel, Switzerland, 4031|
|Istituto Oncologico Svizzera Italiana IOSI|
|Bellinzona, Switzerland, 6500|
|Bern, Switzerland, 3010|
|Chur, Switzerland, CH-7000|
|Hopital Fribourgeois HFR|
|Fribourg, Switzerland, 1708|
|Liestal, Switzerland, CH-4410|
|Luzerne, Switzerland, CH-6000|
|Spital Thurgau AG|
|Münsterlingen, Switzerland, 8596|
|Kantonsspital St. Gallen|
|St. Gallen, Switzerland, 9007|
|Thun, Switzerland, 3600|
|Winterthur, Switzerland, 8401|
|Onkozentrum Hirslanden Zürich|
|Zurich, Switzerland, 8032|
|OnkoZentrum Zürich AG - Klinik im Park|
|Zürich, Switzerland, 8038|
|Zürich, Switzerland, 8091|
|Study Chair:||Thilo Zander, MD||Luzerner Kantonsspital|
|Study Chair:||Christoph Driessen, Prof||Cantonal Hospital of St. Gallen|
|Study Chair:||Christoph Renner, Prof||Onkozentrum Zürich|