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

Sponsor

Amsterdam UMC, location VUmc (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05555329

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma in Relapse Multiple Myeloma Multiple Myeloma, Refractory	Drug: Pomalidomide 4 mg every day in cycle 1 Drug: Pomalidomide 4 mg every other day in cycle 2 Drug: Pomalidomide 2 mg every day in cycle 2 Drug: Pomalidomide 2 mg every day in cycle 3 Drug: Pomalidomide 4 mg every other day in cycle 3	Phase 4

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group A; Pomalidomide 4 mg every other day in cycle 2 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.	Drug: Pomalidomide 4 mg every day in cycle 1 Pomalidomide 4 mg every day, on days 1-21 in a cycle of 28 days Other Names: Cycle 1 Drug: Pomalidomide 4 mg every other day in cycle 2 Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days Other Names: Cycle 2 (Group A) Drug: Pomalidomide 2 mg every day in cycle 3 Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days Other Names: Cycle 3 (Group A)
Experimental: Group B; Pomalidomide 4 mg every other day in cycle 3 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.	Drug: Pomalidomide 4 mg every day in cycle 1 Pomalidomide 4 mg every day, on days 1-21 in a cycle of 28 days Other Names: Cycle 1 Drug: Pomalidomide 2 mg every day in cycle 2 Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days Other Names: Cycle 2 (Group B) Drug: Pomalidomide 4 mg every other day in cycle 3 Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days Other Names: Cycle 3 (Group B)

Arm

Intervention/Treatment

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

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.

Drug: Pomalidomide 4 mg every day in cycle 1

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

Other Names:

Cycle 1

Drug: Pomalidomide 4 mg every other day in cycle 2

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

Other Names:

Cycle 2 (Group A)

Drug: Pomalidomide 2 mg every day in cycle 3

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

Other Names:

Cycle 3 (Group A)

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

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.

Drug: Pomalidomide 4 mg every day in cycle 1

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

Other Names:

Cycle 1

Drug: Pomalidomide 2 mg every day in cycle 2

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

Other Names:

Cycle 2 (Group B)

Drug: Pomalidomide 4 mg every other day in cycle 3

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

Other Names:

Cycle 3 (Group B)

Outcome Measures

Primary Outcome Measures

The AUC/MIC ratio [During three cycles of 28 days]
The 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 Ctrough [During three cycles of 28 days]
The 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 Outcome Measures

Cmax [During three cycles of 28 days]
The 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.
Time above EC50 [During three cycles of 28 days]
The 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.
Toxicity and side effects [During three cycles of 28 days]
Toxicity 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 days]
Overall response rate (ORR), based on the IMWG criteria

Other Outcome Measures

Explorative endpoint: T-cell activation [During three cycles of 28 days]
T-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: Ikaros/Aiolos degradation [During three cycles of 28 days]
Ikaros/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: Concentration of pomalidomide in PBMCs [During three cycles of 28 days]
Concentration 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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