Tasquinimod for the Treatment of Relapsed or Refractory Myeloma

Sponsor
University of Pennsylvania (Other)
Overall Status
Recruiting
CT.gov ID
NCT04405167
Collaborator
Active Biotech AB (Industry)
34
1
4
46.7
0.7

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
34 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Intervention Model Description:
Open label phase 1 study with pilot expansion cohorts at the maximum tolerated doseOpen 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 :
Jul 10, 2020
Anticipated Primary Completion Date :
Jun 1, 2023
Anticipated Study Completion Date :
Jun 1, 2024

Arms and Interventions

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 Names:
  • 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 Names:
  • Ixazomib, Lenalidomide, Dexamethasone
  • Outcome Measures

    Primary Outcome Measures

    1. Optimal Dose [approximately 3 years]

      Maximum tolerated dose of single agent tasquinimod (mg).

    Secondary Outcome Measures

    1. Preliminary Single-Agent Toxicity Profile [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 [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 [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 [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)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    4. Cytotoxic chemotherapy within 3 weeks prior to the initiation of study treatment

    5. Proteasome inhibitors, Imids, or monoclonal antibodies within 2 weeks prior to the initiation of study treatment

    6. Experimental therapy within 4 weeks or 5 half-lives, whichever is shorter

    7. Systemic corticosteroids >=10 mg prednisone or equivalent within 7 days prior to the initiation of study treatment

    8. Radiotherapy within 7 days prior to initiating study treatment

    9. Plasmapheresis within 4 weeks prior to the initiation of study treatment

    10. Tasquinimod at any time

    11. Known central nervous system involvement by myeloma

    12. Diagnosis of smoldering multiple myeloma

    13. Diagnosis of POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

    14. Active plasma cell leukemia

    15. Symptomatic primary (AL) amyloidosis

    16. Diagnosis of myelodysplastic syndrome or myeloproliferative syndrome

    17. Active other malignancy

    18. Major surgery within 4 weeks prior to initiating study treatment

    19. Evidence of severe or currently uncontrolled cardiovascular condition

    20. Ongoing or active systemic infection that requires systemic antibiotic or parenteral anti-infective therapy

    21. Active tuberculosis, active hepatitis A, B or C virus infection, or known human immunodeficiency virus (HIV) positive

    22. History of pancreatitis

    23. History of malabsorption or other condition that would interfere with absorption of study drugs

    24. 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)

    25. 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)

    26. Need for ongoing therapy with drug substances of narrow therapeutic range metabolized mainly by CYP1A2 (duloxetine, alosetron, theophylline, tizanidine, ondansetron)

    27. Ongoing treatment with warfarin, unless the INR is <=3.0.

    28. For subjects enrolled on the IRd combination arms, prior dose-limiting toxicity with lenalidomide or ixazomib or absolute contraindication to concomitant thrombosis prophylaxis

    29. Peripheral neuropathy grade ≥2 (NCI-CTCAE)

    30. Known hypersensitivity to tasquinimod or any excipients in the study treatments

    31. Pregnant or nursing (lactating) women

    32. 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

    33. Prior inclusion in this study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Pennsylvania Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • University of Pennsylvania
    • Active Biotech AB

    Investigators

    • Principal Investigator: Dan Vogl, MD, University of Pennsylvania

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    University of Pennsylvania
    ClinicalTrials.gov Identifier:
    NCT04405167
    Other Study ID Numbers:
    • 842603, UPCC 45419
    • UPCC 45419
    First Posted:
    May 28, 2020
    Last Update Posted:
    Jul 5, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Jul 5, 2022