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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05555329
Other study ID # POMAlternative
Secondary ID
Status Not yet recruiting
Phase Phase 4
First received
Last updated
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
Health authority
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

Study Design


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
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