Clinical trial NCT05555329: Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Myeloma in Relapse
Multiple Myeloma
Multiple Myeloma, Refractory
Keywords: Multiple myeloma
Pomalidomide
Pharmacokinetics/dynamics
Cost-effectiveness
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2022-09-26
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: The AUC/MIC ratio
timeFrame: During three cycles of 28 days
measure: The level of the Ctrough
timeFrame: During three cycles of 28 days
Secondary outcomes:
measure: Cmax
timeFrame: During three cycles of 28 days
measure: Time above EC50
timeFrame: During three cycles of 28 days
measure: Toxicity and side effects
timeFrame: During three cycles of 28 days
measure: Overall response rate (ORR)
timeFrame: During three cycles of 28 days
Other outcomes:
measure: Explorative endpoint: T-cell activation
timeFrame: During three cycles of 28 days
measure: Explorative endpoint: Ikaros/Aiolos degradation
timeFrame: During three cycles of 28 days
measure: Explorative endpoint: Concentration of pomalidomide in PBMCs
timeFrame: During three cycles of 28 days
Locations:
city: Amsterdam
country: Netherlands
facility: VUMedicalCenter
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Sonja Zweegman, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: