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

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma; Multiple Myeloma in Relapse; Multiple Myeloma, Refractory
• Intervention / Treatment: 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 3; Drug: Pomalidomide 2 mg every day in cycle 2; Drug: Pomalidomide 4 mg every other day in cycle 3

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • VUMedicalCenter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The AUC/MIC ratio	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.	During three cycles of 28 days
The level of the Ctrough	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.	During three cycles of 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	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.	During three cycles of 28 days
Time above EC50	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.	During three cycles of 28 days
Toxicity and side effects	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.	During three cycles of 28 days
Overall response rate (ORR)	Overall response rate (ORR), based on the IMWG criteria	During three cycles of 28 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explorative endpoint: T-cell activation	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.	During three cycles of 28 days
Explorative endpoint: Ikaros/Aiolos degradation	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.	During three cycles of 28 days
Explorative endpoint: Concentration of pomalidomide in PBMCs	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.	During three cycles of 28 days

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Investigators: Principal Investigator: Sonja Zweegman, MD PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Actual): February 14, 2024
• Study Completion (Actual): February 14, 2024

Study Registration Dates

• First Submitted: September 20, 2022
• First Submitted That Met QC Criteria: September 23, 2022
• First Posted (Actual): September 26, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 16, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Multiple myeloma; Pomalidomide; Cost-effectiveness; Pharmacokinetics/dynamics
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Leprostatic Agents; Pomalidomide; Thalidomide
• Other Study ID Numbers: POMAlternative

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No