Clinical Trials /

Tasquinimod for the Treatment of Relapsed or Refractory Myeloma

NCT04405167

Description:

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

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Tasquinimod for the Treatment of Relapsed or Refractory Myeloma
  • Official Title: Phase 1 Study of Tasquinimod Alone and in Combination With Standard Therapy for Relapsed or Refractory Myeloma

Clinical Trial IDs

  • ORG STUDY ID: 842603
  • SECONDARY ID: UPCC 45419
  • NCT ID: NCT04405167

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
TasquinimodA1: Tasquinimod single agent dose escalation
IRd chemotherapyIxazomib, Lenalidomide, DexamethasoneB1: Tasquinimod+IRd dose escalation

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
A1: Tasquinimod single agent dose escalationExperimentalThere 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.
  • Tasquinimod
A2: Tasquinimod single agent expansionExperimentalAdditional 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.
  • Tasquinimod
B1: Tasquinimod+IRd dose escalationExperimentalDose 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.
  • Tasquinimod
  • IRd chemotherapy
B2: Tasquinimod+IRd expansionExperimentalAdditional 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.
  • Tasquinimod
  • IRd chemotherapy

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Optimal Dose
Time Frame:approximately 3 years
Safety Issue:
Description:Maximum tolerated dose of single agent tasquinimod (mg).

Secondary Outcome Measures

Measure:Preliminary Single-Agent Toxicity Profile
Time Frame:approximately 3 years
Safety Issue:
Description: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)
Measure:Preliminary Combination Therapy Toxicity Profile
Time Frame:approximately 3 years
Safety Issue:
Description: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)
Measure:Preliminary Single-Agent Response
Time Frame:approximately 3 years
Safety Issue:
Description:Percentage of subjects achieving a partial response or better with single-agent tasquinimod (using the response criteria of the International Myeloma Working Group)
Measure:Preliminary Assessment of Clinical Response Combination Therapy
Time Frame:approximately 3 years
Safety Issue:
Description: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)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University of Pennsylvania

Last Updated

May 26, 2020