Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma

The drug being tested in this study was Alisertib. Alisertib was tested to treat people who
have relapsed/refractory peripheral T-cell lymphoma (PTCL).

This study evaluated alisertib for the improvement in overall response rate (ORR) compared
with single-agent treatment, as selected by the investigator from the offered options of
pralatrexate, romidepsin (US only), or gemcitabine, in participants with relapsed or
refractory PTCL.

The study enrolled 271 patients. Participants were randomized (1:1) to one of 2 treatment
arms:

- Alisertib

- Investigator's choice (Pralatrexate, Romidepsin, or Gemcitabine)

This multi-center trial was conducted worldwide. The overall time to participate in this
study was approximately 5 years. Participants made multiple visits to the clinic, and then
were contacted by telephone up to 42-months after the last participant was randomized, or
until death, for follow-up assessment.

Inclusion Criteria:

- Male or female participants age 18 or older

- Participants with Peripheral T cell lymphoma (PTCL) (selected subtypes) according to
World Health Organization (WHO) criteria and have relapsed or are refractory to at
least 1 prior systemic, cytotoxic therapy for PTCL. Participants must have received
conventional therapy as a prior therapy. Cutaneous-only disease is not permitted.
Participants must have documented evidence of progressive and measurable disease.

- Tumor biopsy available for central hematopathologic review

- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

- Female participants who are post menopausal for at least 1 year, surgically sterile,
or agree to practice 2 effective methods of contraception through 30 days after the
last dose of study drug or agree to abstain from heterosexual intercourse.

- Male participants who agree to practice effective barrier contraception through 6
months after the last dose of alisertib or agree to abstain from heterosexual
intercourse

- Suitable venous access

- Voluntary written consent

Exclusion Criteria

- Known central nervous system lymphoma

- Systemic antineoplastic therapy, immunotherapy, investigational agent or radiation
therapy within 4 weeks of first dose of study treatment or concomitant use during
study

- Prior administration of an Aurora A kinase-targeted agent, including alisertib; or all
of the 3 comparator drugs (pralatrexate, or romidepsin or gemcitabine; or known
hypersensitivity)

- History of uncontrolled sleep apnea syndrome or other conditions that could result in
excessive daytime sleepiness

- Cardiac condition as specified in study protocol, including left ventricular ejection
fraction (LVEF) <40%

- Concomitant use of other medicines as specified in study protocol

- Participants with abnormal gastric or bowel function who require continuous treatment
with H2-receptor antagonists or proton pump inhibitors

- Known active infection with human immunodeficiency virus (HIV), hepatitis B virus, or
hepatitis C

- Autologous stem cell transplant less than 3 months prior to enrollment

- Participants who have undergone allogeneic stem cell or organ transplantation any time

- Inadequate blood levels, bone marrow or other organ function as specified in study
protocol

- The participant must have recovered to National Cancer Institute Common Terminology
Criteria for Adverse Events (NCI CTCAE) Grade ≤ 1 toxicity, to participant's baseline
status (except alopecia), or deemed irreversible from the effects of prior cancer
therapy

- Major surgery, serious infection, or infection requiring systemic antibiotic therapy
within 14 days prior to the first dose of study treatment

- Female participants who are breastfeeding or pregnant

- Coexistent second malignancy or history of prior solid organ malignancy within
previous 3 years

- Serious medical or psychiatric illness or laboratory abnormality that could, in the
investigator's opinion, potentially interfere with the completion of treatment
according to the protocol