Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma
Condition: Relapsed Peripheral T-Cell Lymphoma; Refractory Peripheral T-Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral
Intervention: Alisertib; Pralatrexate; Gemcitabine; Romidepsin
Intervention description: Alisertib enteric coated tablets; Pralatrexate IV infusion; Gemcitabine IV infusion; Romidepsin IV infusion
Intervention MeSH terms: Gemcitabine; Romidepsin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 271.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      This is a phase 3, randomized, 2-arm, open-label, international trial evaluating alisertib
      compared with single-agent treatment, as selected by the investigator from the offered
      options of pralatrexate or gemcitabine or romidepsin, in participants with relapsed or
      refractory peripheral T-cell lymphoma (PTCL). Note: romidepsin was not used as a single-agent
      comparator outside the United States of America (USA) as supply was not available.
    

Eligibility criteria:

        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