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

Amsterdam UMC, location VUmc

Status and phase: Completed; Phase 4

Conditions: Multiple Myeloma in Relapse; Multiple Myeloma; Multiple Myeloma, Refractory

Treatments: Drug: Pomalidomide 4 mg every day in cycle 1; Drug: Pomalidomide 4 mg every other day in cycle 3; Drug: Pomalidomide 2 mg every day in cycle 3; Drug: Pomalidomide 2 mg every day in cycle 2; Drug: Pomalidomide 4 mg every other day in cycle 2

Study type: Interventional

Funder types: Other

Identifiers

NCT05555329

POMAlternative

Details and patient eligibility

About

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.

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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12 participants in 2 patient groups

Group A; Pomalidomide 4 mg every other day in cycle 2

Experimental group

Description:

Group A (6 patients): Cycle 1: Pomalidomide 4 mg every day on day 1-21; Cycle 2: 4 mg every other day on day 1-21; Cycle 3: 2 mg every day on day 1-28. In Cycles of 28 days.

Treatment:

Drug: Pomalidomide 4 mg every other day in cycle 2

Drug: Pomalidomide 2 mg every day in cycle 3

Drug: Pomalidomide 4 mg every day in cycle 1

Group B; Pomalidomide 4 mg every other day in cycle 3

Experimental group

Description:

Group B (6 patients): Cycle 1: Pomalidomide 4 mg every day on day 1-21; Cycle 2: 2 mg every day on day 1-28; Cycle 3: 4 mg every other day on day 1-21. In Cycles of 28 days.

Treatment:

Drug: Pomalidomide 2 mg every day in cycle 2

Drug: Pomalidomide 4 mg every other day in cycle 3

Drug: Pomalidomide 4 mg every day in cycle 1