Study of MLN8237 in Participants With Advanced Hematological Malignancies
Condition: B-cell Follicular Lymphoma; B-cell Marginal Zone Lymphoma; Diffuse Large B-cell Lymphoma; B-cell Mantle Cell Lymphoma; B-cell Small Lymphocytic Lymphoma; B-Cell Chronic Lymphocytic Leukemia; Multiple Myeloma; Waldenstrom's Macroglobulinemia; Noncutaneous Peripheral T-cell Lymphoma Not Otherwise Specified; Angioimmunoblastic T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Enteropathy Associated T-cell Lymphoma; NK Lymphoma
MeSH terms: Lymphoma; Multiple Myeloma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, Large B-Cell, Diffuse; Hematologic Neoplasms; Waldenstrom Macroglobulinemia; Lymphoma, Large-Cell, Anaplastic; Enteropathy-Associated T-Cell Lymphoma; Immunoblastic Lymphadenopathy
Intervention: Alisertib
Intervention description: Alisertib (MLN8237) PIC or ECT
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 58.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug therapy

Summary:

      This is an open-label, multicenter, phase 1 study of MLN8237 in participants with advanced
      hematological malignancies for whom there are limited standard treatment options.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Relapsed or refractory disease and a histologically or cytologically confirmed
             hematological malignancy of the following type for which standard curative treatment
             does not exist or is no longer effective:

               -  B-cell Follicular lymphoma

               -  B-cell Marginal zone lymphoma

               -  Diffuse large B-cell lymphoma

               -  B-cell Mantle cell lymphoma

               -  B-cell Small lymphocytic lymphoma (SLL)

               -  B-Cell Chronic lymphocytic leukemia (B-CLL)

               -  Multiple myeloma

               -  Waldenstrom's macroglobulinemia

               -  Noncutaneous peripheral T-cell lymphoma not otherwise specified (PTCL-NOS)

               -  Angioimmunoblastic T-cell lymphoma (AITL), anaplastic large cell lymphoma,
                  enteropathy associated T-cell lymphoma (EATCL), NK lymphoma (NKL)

          -  Participants with diffuse large B-cell lymphoma must have failed, be ineligible for,
             or have refused an autologous stem cell transplant. There is no restriction regarding
             the maximum number of prior regimens.

          -  Aged 18 years or older

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2

          -  Radiographically or clinically evaluable disease for Part 1 of this study and
             measurable disease for Part 2 of this study

          -  Suitable venous access for the conduct of blood sampling for MLN8237 pharmacokinetics
             (PK)

          -  Recovered from the reversible effects of prior antineoplastic treatment (with the
             exception of alopecia and Grade 1 neuropathy)

        Exclusion Criteria:

          -  Pregnant or lactating

          -  Treatment with clinically significant enzyme inducers within 14 days prior to the
             first dose of MLN8237 as specified in the protocol

          -  Prior allogeneic bone marrow (or other organ) transplantation

          -  Newly diagnosed or uncontrolled cancer-related central nervous system (CNS) disease

          -  Systemic antineoplastic treatment within 21 days preceding the first dose of study
             treatment. Exceptions requiring a 42-day recovery period from last treatment include:
             Nitrosoureas, mitomycin C or Rituximab, alemtuzumab (Campath®), or other unconjugated
             therapeutic antibody (21 days if clear evidence of progressive disease)

          -  Treatment with radioimmunoconjugates or toxin immunoconjugates such as ibritumomab
             tiuxetan (Zevalin™), or tositumomab (Bexxar®) within 56 days preceding the first dose
             of study treatment

          -  Antineoplastic treatment with glucocorticoids within 21 days preceding the first dose
             of study treatment

          -  Radiotherapy involving <25% of the hematopoietically active bone marrow within 21 days
             preceding first dose of study treatment

          -  Radiotherapy involving ≥25% of the hematopoietically active bone marrow within 42 days
             preceding first dose of study treatment

          -  Inability to swallow capsules or known gastrointestinal (GI) disease or GI procedures
             that could interfere with the oral absorption or tolerance of MLN8237. Examples
             include, but are not limited to, partial gastrectomy, history of small intestine
             surgery, and celiac disease.

          -  History of uncontrolled sleep apnea syndrome and other conditions that could result in
             excessive daytime sleepiness such as severe chronic obstructive pulmonary disease

          -  Known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface
             antigen-positive status, or known or suspected active hepatitis C infection. Testing
             is not required in the absence of clinical findings or suspicion.

          -  Participants who fail to meet laboratory values as specified in the protocol during
             the screening period