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

NCT05555329 | Completed Phase 4

• 1 other identifier: POMAlternative
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma; Multiple Myeloma, Refractory

Keywords

Multiple myeloma; Pomalidomide; Pharmacokinetics/dynamics; Cost-effectiveness

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Cmax

  During three cycles of 28 days

• Time above EC50

  During three cycles of 28 days

• Toxicity and side effects

  During three cycles of 28 days

• Overall response rate (ORR)

  During three cycles of 28 days

Other Outcomes (3)

• Explorative endpoint: T-cell activation

  During three cycles of 28 days

• Explorative endpoint: Ikaros/Aiolos degradation

  During three cycles of 28 days

• Explorative endpoint: Concentration of pomalidomide in PBMCs

  During three cycles of 28 days

Study Arms (2)

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

EXPERIMENTAL

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

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

EXPERIMENTAL

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

Interventions

Pomalidomide 4 mg every day in cycle 1 DRUG

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

Also known as: Cycle 1

Group A; Pomalidomide 4 mg every other day in cycle 2; Group B; Pomalidomide 4 mg every other day in cycle 3

Pomalidomide 4 mg every other day in cycle 2 DRUG

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

Also known as: Cycle 2 (Group A)

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

Pomalidomide 2 mg every day in cycle 2 DRUG

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

Also known as: Cycle 2 (Group B)

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

Pomalidomide 2 mg every day in cycle 3 DRUG

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

Also known as: Cycle 3 (Group A)

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

Pomalidomide 4 mg every other day in cycle 3 DRUG

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

Also known as: Cycle 3 (Group B)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VUMedicalCenter

Amsterdam, Netherlands

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Sonja Zweegman, MD PhD

  Amsterdam UMC, location VUmc

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD, Professor of Hematology

Study Record Dates

• First Submitted: September 20, 2022
• First Posted: September 26, 2022
• Study Start: December 1, 2022
• Primary Completion: February 14, 2024
• Study Completion: February 14, 2024
• Last Updated: April 22, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)