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Alternate Day Dosing of Pomalidomide in Patients With Refractory Multiple Myeloma (OptiPOM)

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ClinicalTrials.gov Identifier: NCT03520985
Recruitment Status : Recruiting
First Posted : May 10, 2018
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
Swiss Group for Clinical Cancer Research

Brief Summary:
Pomalidomide is an approved treatment for refractory multiple myeloma. Toxicity of pomalidomide in the pivotal MM-003 trial, 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 is too toxic, and that strategies to deliver reduced dosing of pomalidomide are of high practical relevance. The aim of this trial therefore is to establish that alternate day dosing of pomalidomide (4 mg q2d, d1-28) is non-inferior to daily dosing (4 mg d1-21 q28) in terms of efficacy of the drug with potentially less side effects.

Condition or disease Intervention/treatment Phase
Refractory Multiple Myeloma Drug: Pomalidomide Drug: Dexamethasone Phase 2

Detailed Description:

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.


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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Pomalidomide
The treatment in this trial consists of oral pomalidomide on alternate days (ad) plus Low-Dose Dexamethasone (adPOM + LD-DEX)
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.





Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. Overall Survival (OS) at 12 months [ Time Frame: at 12 months ]
    OS, as defined above, will be evaluated at 12 months.

  3. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

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


Contacts
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Contact: Andrea Fuhrer, PhD +41 31 389 91 91 trials@sakk.ch

Locations
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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         
Sponsors and Collaborators
Swiss Group for Clinical Cancer Research
Investigators
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Study Chair: Thilo Zander, MD Luzerner Kantonsspital
Study Chair: Christoph Driessen, Prof Cantonal Hospital of St. Gallen
Study Chair: Christoph Renner, Prof Onkozentrum Zürich

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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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Swiss Group for Clinical Cancer Research:
refractory Multiple Myeloma
Phase II
Pomalidomide
OptiPOM

Additional relevant MeSH terms:
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Multiple Myeloma
Thalidomide
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
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