Intervention: Alisertib
Trial phase: Phase 1
SMILES: COc1cc(Nc2ncc3c(n2)-c2ccc(Cl)cc2C(c2c(F)cccc2OC)=NC3)ccc1C(=O)O
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 28
Group description: Alisertib 40 mg, Enteric-coated Tablet (ECT) formulation, orally, QD for 14 days followed by a 14-day recovery period in 28-day cycles, or alisertib 30, 40 or 50 mg ECT, orally BID for 7 days followed by a 14-day recovery period in 21-day cycles, until disease progression or unacceptable alisertib-related toxicity (up to 15 cycles).
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