Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma (OptiPOM)
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| ClinicalTrials.gov Identifier: NCT03520985 |
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Recruitment Status :
Recruiting
First Posted : May 10, 2018
Last Update Posted : January 23, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Refractory Multiple Myeloma | Drug: Pomalidomide Drug: Dexamethasone | Phase 2 |
Multiple myeloma (MM) accounts for 1% of all cancers and ∼10% of all hematological malignancies. Despite recent advances in myeloma treatment, including the introduction of proteasome inhibitors, immunomodulatory drugs (IMiDs) and stem cell transplantation, myeloma remains an incurable disease. The treatment of bortezomib and lenalidomide refractory myeloma is still an unmet medical need. Once patients have relapsed after IMiD-containing therapies and have become bortezomib-resistant, their prognosis is extremely poor.
Pomalidomide is a third-generation, Swissmedic approved, oral immunomodulatory drug with activity in such patients. Toxicity of pomalidomide in the pivotal MM-003 trial, however, was considerable, with 60% of patients experiencing drug-related G3/4 toxicity. Neutropenia (48% vs 16%) and pneumonia (13% vs 8%) were significantly more common in the pomalidomide arm. This resulted in frequent dose interruptions (67%) and dose reductions (27%). This suggests that for the majority of patients the 4 mg daily dosing schedule (4 mg daily on 21 of 28 days) is toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance.
Alternative dosing schedules There are robust data available that lower pomalidomide doses (e.g. 2 mg daily) lead to similar responses and progression free survival with fewer side effects. Due to its unique pharmacological characteristics, pomalidomide is well suited for alternate day dosing. The decline of the plasma concentration at the terminal phase is slow. These data make pomalidomide an ideal candidate for alternate day dosing. Therefore, a Phase 1 study has already been conducted in 2008 to test the alternating administration of the drug showing excellent responses with a marked reduction of thrombotic events and less severe myelosuppression.
The drug costs of pomalidomide are high (Switzerland: 12.400 CHF per 4 week cycle; US: 13.700 US$ per 4 week cycle). Interestingly, the manufacturer chose a pricing model that is independent from the capsule strength (costs for one capsule 1 mg=2 mg=3 mg=4 mg). In patients requiring dose reductions due to hematologic toxicity, daily dosing of reduced strength pomalidomide (e.g. 2 mg daily) is approved and suggested by the manufacturer. This delivers 50% less pomalidomide to the patient, albeit at 100% of the price of full dosing.
In summary, the establishment of the modified pomalidomide schedule would be an interesting option for our patients to achieve similar efficacy with fewer side effects. In addition optimizing the cost-effectiveness of the drug.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 110 participants |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma. A Multi-center, Single Arm Phase II Trial |
| Actual Study Start Date : | October 1, 2018 |
| Estimated Primary Completion Date : | March 2023 |
| Estimated Study Completion Date : | December 2025 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Pomalidomide
The treatment in this trial consists of oral pomalidomide on alternate days (ad) plus Low-Dose Dexamethasone (adPOM + LD-DEX)
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Drug: Pomalidomide
Pomalidomide (4 mg p.o.) will be administered on every other day of each 28-day treatment cycle. Treatment duration: Treatment cycles are repeated until disease progression. Other Name: Imnovid® Drug: Dexamethasone For patients ≤ 75 years of age: Low-Dose Dexamethasone (40 mg p.o.) will be administered once per day on Days 1, 7, 15, and 21 of a 28-day cycle. For patients > 75 years of age: Low-Dose Dexamethasone (20 mg p.o.) will be administered once per day on Days 1, 7, 15, and 21 of a 28-day cycle. Treatment duration: Treatment cycles are repeated until disease progression. |
- Overall Response Rate (ORR) [ Time Frame: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months ]OR is defined as minimal response or better, assessed according to the IMWG criteria.
- Overall Survival (OS) [ Time Frame: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months ]OS is defined as the time from registration until death from any cause. Patients not having an event at the time of analysis will be censored at the date they were last known to be alive.
- Overall Survival (OS) at 12 months [ Time Frame: at 12 months ]OS, as defined above, will be evaluated at 12 months.
- Progression-free survival (PFS) [ Time Frame: From date of registration until 28 days after last dose of trial medication with longest treatment time of approximately 36 months ]PFS is defined as the time from registration until progression according the IMWG criteria or death from any cause, whichever occurs first. Patients not having an event at the time of analysis as well as patients starting a new anticancer therapy in the absence of an event will be censored at the date of their last tumor assessment showing non-progression before starting a new treatment, if any.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Key inclusion criteria:
- Patient was diagnosed with multiple myeloma based on standard IMWG criteria
- Prior treatment with ≥ 2 treatment lines of anti-myeloma therapy
- Patients must have failed both lenalidomide and bortezomib
- Measurable disease for myeloma defined as one of the following: serum M-protein ≥ 5 g/L; urine M-protein ≥ 0.2 g/24 hours
- Refractory or relapsed and refractory disease defined as documented disease progression during or within 60 days of completing their last myeloma therapy.
- Adequate hematological, hepatic and renal function
- A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential
Key exclusion criteria:
- History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration, with the exception of pT1-2 prostate cancer Gleason score <6, adequately treated, cervical carcinoma in situ or localized non-melanoma skin cancer.
- Polyneuropathy grade > 2
- Patients who received any of the following within the last 14 days of initiation of trial treatment:
- Plasmapheresis
- Major surgery (kyphoplasty is not considered major surgery)
- Radiation therapy
- Use of any anti-myeloma drug therapy
- Known or clinically suspected Myeloma manifestations in the central nervous system
- Severe or uncontrolled cardiovascular disease
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03520985
| Contact: Andrea Fuhrer, PhD | +41 31 389 91 91 | trials@sakk.ch |
| Switzerland | |
| Kantonspital Aarau | Recruiting |
| Aarau, Switzerland, CH-5001 | |
| Contact: Marc Heizmann, MD +41 62 838 60 50 marc.heizmann@ksa.ch | |
| Principal Investigator: Marc Heizmann, MD | |
| Kantonsspital Baden (Baden/Brugg) | Recruiting |
| Baden, Switzerland, 5404 | |
| Contact: Veronika Ballova, MD +41 56 486 27 62 veronika.ballova@ksb.ch | |
| Principal Investigator: Veronika Ballova, MD | |
| Universitätsspital Basel | Recruiting |
| Basel, Switzerland, 4031 | |
| Contact: Sabine Gerull, MD +41 61 265 25 25 sabine.gerull@usb.ch | |
| Principal Investigator: Sabine Gerull, MD | |
| Istituto Oncologico Svizzera Italiana IOSI | Recruiting |
| Bellinzona, Switzerland, 6500 | |
| Contact: Erika Lerch, MD +41 91 811 91 11 erika.lerch@eoc.ch | |
| Principal Investigator: Erika Lerch, MD | |
| Inselspital Bern | Recruiting |
| Bern, Switzerland, 3010 | |
| Contact: Thomas Pabst, Prof. +41 31 632 84 30 thomas.pabst@insel.ch | |
| Principal Investigator: Thomas Pabst, Prof | |
| Kantonsspital Graubuenden | Recruiting |
| Chur, Switzerland, CH-7000 | |
| Contact: Ulrich Mey, MD 41-81-256-7170 ulrich.mey@ksgr.ch | |
| Principal Investigator: Ulrich Mey, MD | |
| Hopital Fribourgeois HFR | Recruiting |
| Fribourg, Switzerland, 1708 | |
| Contact: Daniel Betticher, Prof +41(0)26 426 72 40 daniel.betticher@h-fr.ch | |
| Principal Investigator: Daniel Betticher, Prof | |
| Kantonsspital Liestal | Recruiting |
| Liestal, Switzerland, CH-4410 | |
| Contact: Geneviève Favre, MD +41 61 925 27 11 genevieve.favre@ksbl.ch | |
| Principal Investigator: Geneviève Favre, MD | |
| Kantonsspital Luzern | Recruiting |
| Luzerne, Switzerland, CH-6000 | |
| Contact: Thilo Zander, MD +41 41 205 11 11 thilo.zander@luks.ch | |
| Principal Investigator: Thilo Zander, MD | |
| Spital Thurgau AG | Recruiting |
| Münsterlingen, Switzerland, 8596 | |
| Contact: Christian Taverna, MD +41 71 686 22 02 christian.taverna@stgag.ch | |
| Principal Investigator: Christian Taverna, MD | |
| Kantonsspital St. Gallen | Recruiting |
| St. Gallen, Switzerland, 9007 | |
| Contact: Tobias Silzle, MD +41 71 494 11 11 tobias.silzle@kssg.ch | |
| Principal Investigator: Tobias Silzle, MD | |
| Regionalspital Thun | Withdrawn |
| Thun, Switzerland, 3600 | |
| Kantonsspital Winterthur | Recruiting |
| Winterthur, Switzerland, 8401 | |
| Contact: Natalie Fischer, MD +41 52 266 40 87 natalie.fischer@ksw.ch | |
| Principal Investigator: Natalie Fischer, MD | |
| Onkozentrum Hirslanden Zürich | Recruiting |
| Zurich, Switzerland, 8032 | |
| Contact: Christoph Renner, Prof +41 43 344 33 44 christoph.renner@hirslanden.ch | |
| Principal Investigator: Christoph Renner, Prof | |
| OnkoZentrum Zürich AG - Klinik im Park | Recruiting |
| Zürich, Switzerland, 8038 | |
| Contact: Christoph Renner, Prof +41 43 344 33 33 christoph.renner@ozh.ch | |
| Principal Investigator: Christoph Renner, Prof | |
| Universitätsspital Zürich | Recruiting |
| Zürich, Switzerland, 8091 | |
| Contact: Markus G. Manz, Prof +41 44 255 38 99 markus.manz@usz.ch | |
| Principal Investigator: Markus G. Manz, Prof | |
| Study Chair: | Thilo Zander, MD | Luzerner Kantonsspital | |
| Study Chair: | Christoph Driessen, Prof | Cantonal Hospital of St. Gallen | |
| Study Chair: | Christoph Renner, Prof | Onkozentrum Zürich |
| Responsible Party: | Swiss Group for Clinical Cancer Research |
| ClinicalTrials.gov Identifier: | NCT03520985 History of Changes |
| Other Study ID Numbers: |
SAKK 39/16 - OptiPOM |
| First Posted: | May 10, 2018 Key Record Dates |
| Last Update Posted: | January 23, 2019 |
| Last Verified: | January 2019 |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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refractory Multiple Myeloma Phase II Pomalidomide OptiPOM |
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Thalidomide |
Dexamethasone Dexamethasone acetate Pomalidomide BB 1101 Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents |