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

Multiple Myeloma Clinical Trial

— POMAlternative  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05555329
• Other study ID #: POMAlternative
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: December 1, 2022
• Est. completion date: August 1, 2023

Study information

• Verified date: November 2022
• Source: Amsterdam UMC, location VUmc
• Contact: Maarten R. Seefat, MD
• Phone: +31204444444
• Email: m.seefat[@]amsterdamumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: August 1, 2023
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Multiple Myeloma, Refractory
• Neoplasms, Plasma Cell

Intervention

Drug:
• Pomalidomide 4 mg every day in cycle 1
Pomalidomide 4 mg every day, on days 1-21 in a cycle of 28 days
• 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
• Pomalidomide 2 mg every day in cycle 2
Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days
• Pomalidomide 2 mg every day in cycle 3
Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amsterdam UMC, location VUmc

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall response rate (ORR)	Overall response rate (ORR), based on the IMWG criteria	During three cycles of 28 days