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Tasquinimod for the Treatment of Relapsed or Refractory Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04405167
Recruitment Status : Recruiting
First Posted : May 28, 2020
Last Update Posted : October 1, 2020
Sponsor:
Collaborator:
Active Biotech AB
Information provided by (Responsible Party):
University of Pennsylvania

Brief Summary:
This study is the first study of tasquinimod, an inhibitor of S100A9, in patients with multiple myeloma.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Tasquinimod Drug: IRd chemotherapy Phase 1

Detailed Description:
Tasquinimod has previously been studied as an anti-cancer agent in patients with other cancers, including a phase 3 randomized trial in patients with metastatic prostate cancer that showed an improvement in radiographic progression-free survival. The side effect profile of tasquinimod is well-characterized based on this previous experience. This trial will establish a maximum tolerated dose and optimal schedule for administration of tasquinimod in patients with multiple myeloma and then investigate the maximum tolerated dose of tasquinimod in combination with a standard myeloma regimen of ixazomib, lenalidomide, and dexamethasone (IRd). For both single agent tasquinimod and the combination of tasquinimod with IRd, exploratory expansion cohorts will be enrolled to preliminarily characterize the antimyeloma activity of each regimen.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Open label phase 1 study with pilot expansion cohorts at the maximum tolerated dose
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1 Study of Tasquinimod Alone and in Combination With Standard Therapy for Relapsed or Refractory Myeloma
Actual Study Start Date : July 10, 2020
Estimated Primary Completion Date : June 1, 2023
Estimated Study Completion Date : June 1, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: A1: Tasquinimod single agent dose escalation
There are up to 5 planned dose levels, with 3 de-escalation dose levels available in case dose level 1 is determined to exceed the MTD. This arm will enroll 15-30 subjects if all dose levels are explored.
Drug: Tasquinimod
Tasquinimod will be supplied as oral capsules.

Experimental: A2: Tasquinimod single agent expansion
Additional subjects will enroll in arm A2 at the MTD and optimal schedule, so that 12 subjects total who are evaluable for response will have received the MTD/optimal schedule of single agent tasquinimod. Enrollment in arm A2 will not begin until enrollment in arm A1 has been completed and a single agent MTD/optimal schedule has been established.
Drug: Tasquinimod
Tasquinimod will be supplied as oral capsules.

Experimental: B1: Tasquinimod+IRd dose escalation
Dose levels will be defined according to the same tasquinimod doses as in the single agent (Arm A1) dose escalation. Enrollment in arm B1 will not begin until enrollment in arm A1 has been completed and an MTD/optimal schedule has been established for single agent tasquinimod. Initial subjects in arm B1 will be enrolled at the lower of dose level 1 or one dose level below the single agent MTD . If this initial dose level is determined to exceed the combination MTD, further subjects will be enrolled at one dose level lower. Enrollment is not planned in arm B1 at doses higher than the single agent MTD. There are 9-12 planned subjects if all dose levels are explored.
Drug: Tasquinimod
Tasquinimod will be supplied as oral capsules.

Drug: IRd chemotherapy
IRd chemotherapy with ixazomib, lenalidomide, and dexamethasone
Other Name: Ixazomib, Lenalidomide, Dexamethasone

Experimental: B2: Tasquinimod+IRd expansion
Additional subjects will enroll in arm B2 at the MTD and optimal schedule, so that 12 subjects total who are both evaluable for response and previously refractory to their most recent Imid/PI combination will have received the MTD/optimal schedule of tasquinimod in combination with ixazomib, lenalidomide, and dexamethasone. Enrollment in arm B2 will not begin until enrollment in arm B1 has been completed and a combination MTD/optimal schedule has been established.
Drug: Tasquinimod
Tasquinimod will be supplied as oral capsules.

Drug: IRd chemotherapy
IRd chemotherapy with ixazomib, lenalidomide, and dexamethasone
Other Name: Ixazomib, Lenalidomide, Dexamethasone




Primary Outcome Measures :
  1. Optimal Dose [ Time Frame: approximately 3 years ]
    Maximum tolerated dose of single agent tasquinimod (mg).


Secondary Outcome Measures :
  1. Preliminary Single-Agent Toxicity Profile [ Time Frame: approximately 3 years ]
    Percentage of subjects experiencing treatment-emergent grade 3/4 adverse events during therapy with single-agent tasquinimod (using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 5)

  2. Preliminary Combination Therapy Toxicity Profile [ Time Frame: approximately 3 years ]
    Percentage of subjects experiencing treatment-emergent grade 3/4 adverse events during therapy with tasquinimod, ixazomib, lenalidomide, and dexamethasone (using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE), version 5)

  3. Preliminary Single-Agent Response [ Time Frame: approximately 3 years ]
    Percentage of subjects achieving a partial response or better with single-agent tasquinimod (using the response criteria of the International Myeloma Working Group)

  4. Preliminary Assessment of Clinical Response Combination Therapy [ Time Frame: approximately 3 years ]
    Percentage of subjects achieving a partial response or better with tasquinimod, ixazomib, lenalidomide, and dexamethasone (using the response criteria of the International Myeloma Working Group)



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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

Inclusion Criteria:

  1. Signed informed consent
  2. 18 years of age or older
  3. Multiple myeloma (MM) diagnosed according to IMWG criteria
  4. Measurable disease (this is defined differently in different arms)
  5. Multiple myeloma relapsed or refractory to treatment (this is defined differently in different arms)
  6. Meet certain clinical laboratory criteria
  7. ECOG performance status ≤2
  8. Life expectancy of at least 3 months
  9. For women of childbearing potential, a negative serum or urine pregnancy test prior to study treatment.
  10. For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use two methods of contraception one of which must be highly effective
  11. For men: agreement to use a barrier method of contraception for 1 month before start of study treatment, during the treatment period and for 6 months after the last dose of study treatment.

Exclusion Criteria:

  1. Failure to have fully recovered (i.e. ≤ Grade 1 toxicity) from the effects of prior chemotherapy (except for alopecia)
  2. Active graft versus host disease
  3. Treatment with any of the following:

    1. Cytotoxic chemotherapy within 3 weeks prior to the initiation of study treatment
    2. Proteasome inhibitors, Imids, or monoclonal antibodies within 2 weeks prior to the initiation of study treatment
    3. Experimental therapy within 4 weeks or 5 half-lives, whichever is shorter
    4. Systemic corticosteroids >=10 mg prednisone or equivalent within 7 days prior to the initiation of study treatment
    5. Radiotherapy within 7 days prior to initiating study treatment
    6. Plasmapheresis within 4 weeks prior to the initiation of study treatment
    7. Tasquinimod at any time
  4. Known central nervous system involvement by myeloma
  5. Diagnosis of smoldering multiple myeloma
  6. Diagnosis of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
  7. Active plasma cell leukemia
  8. Symptomatic primary (AL) amyloidosis
  9. Diagnosis of myelodysplastic syndrome or myeloproliferative syndrome
  10. Active other malignancy
  11. Major surgery within 4 weeks prior to initiating study treatment
  12. Evidence of severe or currently uncontrolled cardiovascular condition
  13. Ongoing or active systemic infection that requires systemic antibiotic or parenteral anti-infective therapy
  14. Active tuberculosis, active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positive
  15. History of pancreatitis
  16. History of malabsorption or other condition that would interfere with absorption of study drugs
  17. Systemic treatment within 14 days prior to the initiation of study treatment with moderate or strong inhibitor or moderate or strong inducer of cytochrome P-3A4 (CYP3A4)
  18. Need for ongoing therapy drug substances of narrow therapeutic range that are metabolized mainly by CYP3A4 (alfentanil, fentanyl, quinidine, astemizole, terfenadine, sirolimus, tacrolimus, cyclosporine, cisapride, ergotamine)
  19. Need for ongoing therapy with drug substances of narrow therapeutic range metabolized mainly by CYP1A2 (duloxetine, alosetron, theophylline, tizanidine, ondansetron)
  20. Ongoing treatment with warfarin, unless the INR is <=3.0.
  21. For subjects enrolled on the IRd combination arms, prior dose-limiting toxicity with lenalidomide or ixazomib or absolute contraindication to concomitant thrombosis prophylaxis
  22. Peripheral neuropathy grade ≥2 (NCI-CTCAE)
  23. Known hypersensitivity to tasquinimod or any excipients in the study treatments
  24. Pregnant or nursing (lactating) women
  25. Any other condition that would, in the Investigator's judgment, contraindicate subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures
  26. Prior inclusion in this study

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): NCT04405167


Contacts
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Contact: Harjeet K Sembhi, MPH 215-220-9688 Harjeet.Sembhi@pennmedicine.upenn.edu

Locations
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United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Harjeet K Sembhi, MPH    215-220-9688    Harjeet.Sembhi@pennmedicine.upenn.edu   
Principal Investigator: Dan Vogl, MD         
Sponsors and Collaborators
University of Pennsylvania
Active Biotech AB
Investigators
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Principal Investigator: Dan Vogl, MD University of Pennsylvania
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Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT04405167    
Other Study ID Numbers: 842603
UPCC 45419 ( Other Identifier: University of Pennsylvania )
First Posted: May 28, 2020    Key Record Dates
Last Update Posted: October 1, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Dexamethasone
Lenalidomide
Ixazomib
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
Protease Inhibitors
Enzyme Inhibitors