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

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

NCT ID: NCT05555329

Condition: Multiple Myeloma in Relapse
Multiple Myeloma
Multiple Myeloma, Refractory

Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Thalidomide
Pomalidomide

Conditions: Keywords:
Multiple myeloma
Pomalidomide
Pharmacokinetics/dynamics
Cost-effectiveness

Study type: Interventional

Study phase: Phase 4

Overall status: Unknown status

Study design:

Allocation: Randomized

Intervention model: Crossover Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: Pomalidomide 4 mg every day in cycle 1
Description: Pomalidomide 4 mg every day, on days 1-21 in a cycle of 28 days
Arm group label: Group A; Pomalidomide 4 mg every other day in cycle 2
Arm group label: Group B; Pomalidomide 4 mg every other day in cycle 3

Other name: Cycle 1

Intervention type: Drug
Intervention name: Pomalidomide 4 mg every other day in cycle 2
Description: Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days
Arm group label: Group A; Pomalidomide 4 mg every other day in cycle 2

Other name: Cycle 2 (Group A)

Intervention type: Drug
Intervention name: Pomalidomide 2 mg every day in cycle 2
Description: Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days
Arm group label: Group B; Pomalidomide 4 mg every other day in cycle 3

Other name: Cycle 2 (Group B)

Intervention type: Drug
Intervention name: Pomalidomide 2 mg every day in cycle 3
Description: Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days
Arm group label: Group A; Pomalidomide 4 mg every other day in cycle 2

Other name: Cycle 3 (Group A)

Intervention type: Drug
Intervention name: Pomalidomide 4 mg every other day in cycle 3
Description: Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days
Arm group label: Group B; Pomalidomide 4 mg every other day in cycle 3

Other name: Cycle 3 (Group B)

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.

Criteria for 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Start date: December 1, 2022

Completion date: August 1, 2023

Lead sponsor:
Agency: Amsterdam UMC, location VUmc
Agency class: Other

Source: Amsterdam UMC, location VUmc

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05555329