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Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study

Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day: Reduction in Costs, Same Efficacy? A PKPD Bioequivalence Pilot Study; the POMAlternative Study

Status
Completed
Phases
Phase 4
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT05555329
Acronym
POMAlternative
Enrollment
12
Registered
2022-09-26
Start date
2022-12-01
Completion date
2024-02-14
Last updated
2025-04-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Multiple Myeloma, Multiple Myeloma in Relapse, Multiple Myeloma, Refractory

Keywords

Multiple myeloma, Pomalidomide, Pharmacokinetics/dynamics, Cost-effectiveness

Brief summary

Pomalidomide either as single therapy or in combination with cyclophosphamide, elotuzumab, bortezomib, or daratumumab are effective treatment regimens in relapsed refractory multiple myeloma (RRMM). Standard dosing is 4 mg/day during 21 days of a 28-day cycle (21/28). However, a clear dose-response association for pomalidomide in patients with multiple myeloma (MM) is lacking. There is data supporting that a dose of 2 mg/day continuously (28/28) induces fewer side effects while efficacy is preserved, compared to 4 mg/day continuously. The response in patients who received pomalidomide 2 mg per day compared to 4 mg per day was higher, with a longer duration of response. In addition, a randomized phase II study showed no difference in efficacy between 4 mg (21/28) and 4 mg continuously. These clinical studies support that a dosage of pomalidomide of 2 mg (28/28) is at least comparable with a dosage of 4 mg (21/28). It is not known if 4 mg every other day (EOD) is comparable to a dosage of pomalidomide 2 mg (28/28) or 4 mg every day (QD, 21/28). For cost reasons, this is interesting as the costs of pomalidomide 4 mg and 2 mg are comparable. Therefore, from a patient and societal perspective, the investigators want to explore if an alternative scheme would be possible by performing a PKPD bio-equivalence pilot study.

Detailed description

Pomalidomide either as single therapy or in combination with cyclophosphamide, elotuzumab, bortezomib, or daratumumab are effective treatment regimens in relapsed refractory multiple myeloma (RRMM). Standard dosing is 4 mg/day during 21 days of a 28-day cycle (21/28). However, a clear dose-response association for pomalidomide in patients with multiple myeloma (MM) is lacking. There is data supporting that a dose of 2 mg/day continuously (28/28) induces fewer side effects while efficacy is preserved, compared to 4 mg/day continuously. The response in patients who received pomalidomide 2 mg per day compared to 4 mg per day was higher, with a longer duration of response. In addition, a randomized phase II study showed no difference in efficacy between 4 mg (21/28) and 4 mg continuously. These clinical studies support that a dosage of pomalidomide of 2 mg (28/28) is at least comparable with a dosage of 4 mg (21/28). It is not known if 4 mg every other day (EOD) is comparable to a dosage of pomalidomide 2 mg (28/28) or 4 mg every day (QD, 21/28). For cost reasons, this is interesting as the costs of pomalidomide 4 mg and 2 mg are comparable. Therefore, from a patient and societal perspective, the investigators want to explore if an alternative scheme would be possible by performing a PKPD bio-equivalence pilot study.

Interventions

DRUGPomalidomide 4 mg every day in cycle 1

Pomalidomide 4 mg every day, on days 1-21 in a cycle of 28 days

DRUGPomalidomide 4 mg every other day in cycle 2

Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days

DRUGPomalidomide 2 mg every day in cycle 2

Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days

DRUGPomalidomide 2 mg every day in cycle 3

Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days

DRUGPomalidomide 4 mg every other day in cycle 3

Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days

Sponsors

Amsterdam UMC, location VUmc
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* Patients with relapsed/refractory multiple myeloma, who are eligible for a treatment regimen which contains pomalidomide. Either monotherapy or in combination with bortezomib, daratumumab, cyclophosphamide, or elotuzumab * Patients who received a minimum of two cycles of pomalidomide 4mg every day on day 1-21/28 * Age \> 18 years * WHO performance status 0-3 * Written informed consent

Exclusion criteria

* Usage of CYP1A2 inhibitors (e.g. ciprofloxacin, enoxacin, ketoconazole, carbamazepine, fluvoxamine, and grapefruit juice) * Renal insufficiency requiring dialysis * Significant hepatic dysfunction (total bilirubin \> 330 μmol/l or transaminases \> 3 times normal level) * Current smoker * Hemoglobin \<6.5 mmol/L * Thrombocytes \<100 \*10\^9/L * Neutrophiles \<1.5 \*10\^9/L * Pregnant patients * Female patients who are able to get pregnant and who do not agree to adequate birth control or complete abstinence * Male patients who do not agree to adequate birth control or complete abstinence * Hypersensitivity to pomalidomide or constituents

Design outcomes

Primary

MeasureTime frameDescription
The AUC/MIC ratioDuring three cycles of 28 daysThe AUC/MIC ratio during usage of pomalidomide 4 mg QD on day 1-21, 4 mg EOD on day 1-21, and 2 mg QD on day 1-28 in cycles of 28 days.
The level of the CtroughDuring three cycles of 28 daysThe level of the Ctrough during usage of pomalidomide 4 mg QD on day 1-21, 4 mg EOD on day 1-21, and 2 mg QD on day 1-28 in cycles of 28 days.

Secondary

MeasureTime frameDescription
Time above EC50During three cycles of 28 daysThe time above the EC50 during usage of pomalidomide 4 mg QD on day 1-21, 4 mg EOD on day 1- 21, and 2 mg QD on day 1-28 in cycles of 28 days.
CmaxDuring three cycles of 28 daysThe Cmax during usage of pomalidomide 4 mg QD on day 1-21, 4 mg EOD on day 1- 21, and 2 mg QD on day 1-28 in cycles of 28 days.
Toxicity and side effectsDuring three cycles of 28 daysToxicity and side effects during usage of pomalidomide 4 mg every day on day 1-21, pomalidomide 4 mg every other day on day 1-21, and pomalidomide 2 mg every day on day 1-28 in cycles of 28 days.
Overall response rate (ORR)During three cycles of 28 daysOverall response rate (ORR), based on the IMWG criteria

Other

MeasureTime frameDescription
Explorative endpoint: Ikaros/Aiolos degradationDuring three cycles of 28 daysIkaros/Aiolos degradation as a biological measurement of pomalidomide activation during usage of pomalidomide 4 mg every day on day 1-21, pomalidomide 4 mg every other day on day 1-21, and pomalidomide 2 mg every day on day 1-28 in cycles of 28 days.
Explorative endpoint: T-cell activationDuring three cycles of 28 daysT-cell activation, defined as the expression of membrane activation markers and cytokine markers during usage of pomalidomide 4 mg every day on day 1-21, pomalidomide 4 mg every other day on day 1-21, and pomalidomide 2 mg every day on day 1-28 in cycles of 28 days.
Explorative endpoint: Concentration of pomalidomide in PBMCsDuring three cycles of 28 daysConcentration of pomalidomide in PBMCs during usage of pomalidomide 4 mg every day on day 1-21, pomalidomide 4 mg every other day on day 1-21, and pomalidomide 2 mg every day on day 1-28 in cycles of 28 days.

Countries

Netherlands

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026