A Study of Ixazomib, Given With Dexamethasone in Adults With Multiple Myeloma
Condition: Relapsed and/or Refractory Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Ixazomib; Pomalidomide; Dexamethasone
Intervention description: Ixazomib capsules; Pomalidomide capsules; Dexamethasone tablets
Intervention MeSH terms: Dexamethasone; Pomalidomide; Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 122.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      The main aim of this study is to learn if ixazomib, given with dexamethasone, stops the
      cancer from getting worse in people with relapsed or refractory multiple myeloma. It will be
      compared to another medicine called pomalidomide, given with dexamethasone with people with
      the same condition. Relapsed means the previous cancer treatment stopped working, over time.
      Refractory means they did not respond to previous cancer treatment. Another aim is to check
      for side effects from the study medicines.

      At the first visit, the study doctor will check who can take part. Participants who can take
      part will be picked for 1 of 2 treatments by chance.

        -  Ixazomib capsules, given with dexamethasone tablets

        -  Pomalidomide capsules, given with dexamethasone tablets

      All participants will take their study medicine on specific days during a 28-day cycle.

      The 1st dose of study medicines in each 28-day cycle will take place in the clinic, The other
      doses of the study medicines will be taken at home. This will happen for 6 cycles. After
      this, all study medicines will be taken at home.

      After treatment, participants will visit the clinic every 12 weeks for a check-up.

      If participants cannot attend their clinic for an important reason (for example, due to the
      COVID-19 pandemic), the clinic will make alternative arrangements using their local
      procedures.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Must have a confirmed diagnosis of multiple myeloma (MM) requiring therapy according
             to International Myeloma Working Group (IMWG) criteria.

          2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          3. Must have had a relapse or progressive disease (PD) after having received 2 or more
             prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more
             cycles of a planned treatment program; this may consist of 1 or more planned cycles of
             single-agent therapy or combination therapy, as well as a sequence of treatments
             administered in a planned manner. For example, a planned treatment approach of
             induction therapy followed by autologous stem cell transplantation (SCT), followed by
             maintenance is considered 1 line of therapy. Typically each line of therapy is
             separated by PD. Discussion with the medical monitor may help clarify the number of
             lines of therapy that a prospective study participant had.

          4. Must be refractory to lenalidomide, defined as having received at least 2 consecutive
             cycles of lenalidomide as a single agent or within a lenalidomide-containing regimen
             and having had PD during treatment with or within 60 days after the last dose of
             lenalidomide. The starting dose of lenalidomide should have been 25 mg (or as low as
             10 mg in the case of renal function impairment or other safety concern), and the final
             dose should have been a minimum of 10 mg.

          5. Must have received at least 2 consecutive cycles of a bortezomib- or
             carfilzomib-containing regimen, and either:

               -  Achieved at least a partial response (PR) and did not have PD during treatment
                  with or within 60 days after the last dose of bortezomib or carfilzomib, OR

               -  Had bortezomib and/or carfilzomib intolerance (defined as discontinuation because
                  of drug-related adverse events [AEs] before completion of the planned treatment
                  course) without PD before the start of the next regimen.

          6. Must have measurable disease defined by:

               -  Serum M-protein >=1 g/dL (>=10 g/L), OR

               -  Urine M-protein >=200 mg/24 hours and must have documented MM isotype by
                  immunofixation (central laboratory).

          7. Suitable venous access for the study-required blood sampling, including
             pharmacokinetic (PK) sampling.

          8. Recovered (that is, less than or equal to [<=] Grade 1 nonhematologic toxicity) from
             the reversible effects of prior anticancer therapy.

          9. Must be willing and able to adhere to pomalidomide-related risk mitigation activities
             if randomized to the pom+dex arm (example, Risk Evaluation and Mitigation Strategies
             [REMS], pregnancy prevention programs).

        Exclusion Criteria:

          1. Prior allogenic bone marrow transplantation in any prior line of therapy or prior
             autologous SCT in the last prior line of therapy- unless the autologous SCT was
             performed a year or more before disease progression.

          2. Diagnosed with or treated for another malignancy within 2 years before randomization,
             or previously diagnosed with another malignancy and have any evidence of residual,
             persistent, or recurrent disease. Participants with nonmelanoma skin cancer or
             carcinoma in situ of any type are not excluded if they have undergone complete
             resection.

          3. Diagnosis of smoldering MM, Waldenström's macroglobulinemia, POEMS (polyneuropathy,
             organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome,
             plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or
             myeloproliferative syndrome.

          4. Peripheral neuropathy Grade 1 with pain or Grade 2 or higher peripheral neuropathy of
             any cause on clinical examination during the Screening period.

          5. Treatment with any investigational products or with chimeric or fully human monoclonal
             antibodies within 30 days before randomization, systemic anticancer therapy or
             radiotherapy within 14 days before randomization (Note: "spot" radiation for areas of
             pain is permitted), and major surgery within 14 days before randomization.

          6. Known gastrointestinal disease or gastrointestinal procedure that could interfere with
             the oral absorption or tolerance of study therapy, including difficulty swallowing.

          7. Serious infection requiring parenteral antibiotic therapy or any other serious
             infection within 14 days before randomization.

          8. Central nervous system involvement with MM (by clinical symptoms and signs).

          9. Ongoing or active systemic infection, known human immunodeficiency virus-ribonucleic
             acid (RNA) positive, known hepatitis B surface antigen seropositive, or known
             hepatitis C virus-RNA positive.

         10. Systemic treatment with strong cytochrome P-450 3A inducers (rifampin, rifapentine,
             rifabutin, carbamazepine, phenytoin, phenobarbital) or use of St. John's wort within
             14 days before randomization.

         11. Admission or evidence of illicit drug use, drug abuse, or alcohol abuse.

         12. History of severe cutaneous reactions, including hypersensitivity reactions such as
             Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and Drug Reaction
             with Eosinophilia and Systemic Symptoms (DRESS), in the context of treatment with
             lenalidomide or thalidomide.