Open-label, Phase II Study of MLN9708 in Patients With Relapsed/Refractory Cutaneous and Peripheral T-cell Lymphomas
Condition: Lymphoma, T-Cell
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: MLN9708
Intervention MeSH terms: Ixazomib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      Historically cutaneous and peripheral T-cell lymphomas have response rates of approximately
      30% to standard chemotherapy regimens. We alternatively hypothesize that MLN9708 will be
      active in this disease and will improve best objective response.

      We will also determine the extent to which MLN9708 inhibits GATA-3 (Trans-acting
      T-cell-specific transcription factor) expression, which is associated with poor prognosis,
      and whether GATA-3 expression represents a novel predictive biomarker for MLN9708
      sensitivity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female patients 18 years or older at the time of enrollment.

          -  Voluntary written consent must be given.

          -  Female patients who are postmenopausal for at least 1 year before the screening visit,
             OR surgically sterile, OR agree to practice 2 effective methods of contraception, at
             the same time, through 90 days after the last dose of study drug, AND adhere to the
             guidelines of any treatment-specific pregnancy prevention program, OR agree to
             practice true abstinence.

          -  Male patients must agree to practice effective barrier contraception through 90 days
             after the last dose of study drug, OR adhere to the guidelines of any
             treatment-specific pregnancy prevention program, OR agree to practice true abstinence.

          -  Patients must have histologically proven T-cell lymphoma, including Peripheral T-cell
             lymphoma, Angioimmunoblastic T-cell lymphoma, Anaplastic large cell lymphoma (ALK
             positive), Anaplastic large cell lymphoma (ALK negative), Mycosis fungoides, Sezary
             syndrome.

          -  CTCL patients must have stage IIb-IV disease.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

          -  Absolute neutrophil count (ANC) ≥ 1,000/mm3 and platelet count ≥ 75,000/mm3.

          -  Platelet transfusions are not allowed within 3 days before study enrollment.

          -  Total bilirubin ≤ 1.5 x the upper limit of the normal range (ULN).

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ to 3 x ULN.

          -  Creatinine clearance ≥30 mL/min.

          -  Documented disease progression after receiving at least one prior therapeutic regimen.

        Exclusion Criteria:

          -  Female patients who are lactating or have a positive serum pregnancy test.

          -  Failure to have recovered (ie, less than or equal to Grade 1 toxicity) from the
             reversible effects of prior chemotherapy.

          -  Major surgery within 14 days of enrollment.

          -  Radiotherapy within 14 days of enrollment. If the field is small, 7 days will be
             considered a sufficient interval between treatment and administration of the MLN9708.

          -  Known central nervous system involvement.

          -  Infection requiring systemic intravenous antibiotic therapy or other serious infection
             within 7 days before study enrollment.

          -  Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
             hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure,
             unstable angina, or myocardial infarction within the past 6 months.

          -  Systemic treatment, within 14 days before the first dose of MLN9708, with strong
             inhibitors of CYP1A2, strong inhibitors of CYP3A or strong CYP3A inducers or use of
             Ginkgo biloba or St. John's wort.

          -  Ongoing or active systemic infection, active hepatitis B or C virus infection, or HIV
             positive.

          -  Any serious medical or psychiatric illness that could potentially interfere with the
             completion of treatment according to this protocol.

          -  Known allergy to any of the study medications, their analogues, or excipients.

          -  Known GI disease or GI procedure that could interfere with the oral absorption or
             tolerance of MLN9708 including difficulty swallowing.

          -  Diagnosed or treated for another malignancy within 2 years before study enrollment or
             previously diagnosed with another malignancy and have any evidence of residual
             disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are
             not excluded if they have undergone complete resection.

          -  Patient has greater than or equal to Grade 3 peripheral neuropathy, or Grade 2 with
             pain on clinical examination during the screening period.

          -  Participation in other clinical trials with other investigational agents not included
             in this trial, within 21days of the start of this trial and throughout the duration of
             this trial.

          -  Prior allogeneic hematopoietic stem cell transplant.

          -  Prior autologous hematopoietic stem cell transplant within 90 days of study entry.

          -  Prior treatment with bortezomib.