Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study (POMAlternative)
Primary Purpose
Multiple Myeloma in Relapse, Multiple Myeloma, Multiple Myeloma, Refractory
Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Pomalidomide 4 mg every day in cycle 1
Pomalidomide 4 mg every other day in cycle 2
Pomalidomide 2 mg every day in cycle 2
Pomalidomide 2 mg every day in cycle 3
Pomalidomide 4 mg every other day in cycle 3
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma in Relapse focused on measuring Multiple myeloma, Pomalidomide, Pharmacokinetics/dynamics, Cost-effectiveness
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Group A; Pomalidomide 4 mg every other day in cycle 2
Group B; Pomalidomide 4 mg every other day in cycle 3
Arm 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.
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.
Outcomes
Primary Outcome Measures
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.
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.
Secondary Outcome Measures
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.
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.
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.
Overall response rate (ORR)
Overall response rate (ORR), based on the IMWG criteria
Full Information
NCT ID
NCT05555329
First Posted
September 20, 2022
Last Updated
November 16, 2022
Sponsor
Amsterdam UMC, location VUmc
1. Study Identification
Unique Protocol Identification Number
NCT05555329
Brief Title
Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
December 1, 2022 (Anticipated)
Primary Completion Date
April 1, 2023 (Anticipated)
Study Completion Date
August 1, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Amsterdam UMC, location VUmc
4. Oversight
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
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma in Relapse, Multiple Myeloma, Multiple Myeloma, Refractory
Keywords
Multiple myeloma, Pomalidomide, Pharmacokinetics/dynamics, Cost-effectiveness
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Group A; Pomalidomide 4 mg every other day in cycle 2
Arm Type
Experimental
Arm 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.
Arm Title
Group B; Pomalidomide 4 mg every other day in cycle 3
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Pomalidomide 4 mg every day in cycle 1
Other Intervention Name(s)
Cycle 1
Intervention Description
Pomalidomide 4 mg every day, on days 1-21 in a cycle of 28 days
Intervention Type
Drug
Intervention Name(s)
Pomalidomide 4 mg every other day in cycle 2
Other Intervention Name(s)
Cycle 2 (Group A)
Intervention Description
Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days
Intervention Type
Drug
Intervention Name(s)
Pomalidomide 2 mg every day in cycle 2
Other Intervention Name(s)
Cycle 2 (Group B)
Intervention Description
Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days
Intervention Type
Drug
Intervention Name(s)
Pomalidomide 2 mg every day in cycle 3
Other Intervention Name(s)
Cycle 3 (Group A)
Intervention Description
Pomalidomide 2 mg every day, on days 1-28 in a cycle of 28 days
Intervention Type
Drug
Intervention Name(s)
Pomalidomide 4 mg every other day in cycle 3
Other Intervention Name(s)
Cycle 3 (Group B)
Intervention Description
Pomalidomide 4 mg every other day, on days 1-21 in a cycle of 28 days
Primary Outcome Measure Information:
Title
The AUC/MIC ratio
Description
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.
Time Frame
During three cycles of 28 days
Title
The level of the Ctrough
Description
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.
Time Frame
During three cycles of 28 days
Secondary Outcome Measure Information:
Title
Cmax
Description
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 Frame
During three cycles of 28 days
Title
Time above EC50
Description
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.
Time Frame
During three cycles of 28 days
Title
Toxicity and side effects
Description
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.
Time Frame
During three cycles of 28 days
Title
Overall response rate (ORR)
Description
Overall response rate (ORR), based on the IMWG criteria
Time Frame
During three cycles of 28 days
Other Pre-specified Outcome Measures:
Title
Explorative endpoint: T-cell activation
Description
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.
Time Frame
During three cycles of 28 days
Title
Explorative endpoint: Ikaros/Aiolos degradation
Description
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.
Time Frame
During three cycles of 28 days
Title
Explorative endpoint: Concentration of pomalidomide in PBMCs
Description
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.
Time Frame
During three cycles of 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Maarten R. Seefat, MD
Phone
+31204444444
Email
m.seefat@amsterdamumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sonja Zweegman, MD PhD
Organizational Affiliation
Amsterdam UMC, location VUmc
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
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