Brief Summary

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Official Title: "A Phase 3, Randomized, Two-Arm, Open-Label, Multicenter, International Trial of Alisertib (MLN8237) or Investigator's Choice (Selected Single Agent) in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma"

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 patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Note: romidepsin will not be used as a single-agent comparator in countries that do not permit its use at this time.

• Study Type: Interventional
• Study Design: Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Study Primary Completion Date: March 2017

Interventions Used in this Clinical Trial

• Drug: Alisertib
  • Patients randomized to receive alisertib will be administered an enteric-coated tablet formulation 5×10-mg twice daily orally for 7 consecutive days (Cycle Days 1-7) in a 21-day cycle.
• Drug: Pralatrexate
  • Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate,or Romidepsin, or Gemcitabine. Patients randomized to receive Pralatrexate will be administered the drug at 30mg/m2 as an intravenous (IV) push over 3 to 5 min once weekly for 6 weeks in 7-week cycles with concurrent vitamin B12 and folic acid supplementation. Cycles should be repeated every 7 weeks
• Drug: Gemcitabine
  • Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate, or Romidepsin, or Gemcitabine. Patients randomized to receive Gemcitabine will receive the drug intravenously at 1,000 mg/m2 over 30 minutes on Days 1, 8, and 15 of a 28-day cycle. Cycles should be repeated every 28 days in the absence of disease progression or unacceptable toxicity.
• Drug: Romidepsin
  • Patients randomized to single-agent comparator will be assigned by the investigator to receive ONE of either Pralatrexate, or Romidepsin, or Gemcitabine. Patients randomized to receive Romidepsin will be administered the drug intravenously at 14mg/m2 over a 4-hour period on Days 1,8,& 15 of a 28-cycle. Cycles should be repeated every 28 days.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Alisertib
  • Alisertib
• Active Comparator: Pralatrexate, or Romidepsin, or Gemcitabine
  • Pralatrexate,or Romidepsin,or Gemcitabine

Outcome Measures for this Clinical Trial

Primary Measures

• Number of patients with overall response
  • Time Frame: Change from screening period in response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
    Safety Issue?: No
• Number of patients with PFS
  • Time Frame: Change from screening period in response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
    Safety Issue?: No

Secondary Measures

• Number of patients with complete response + complete response unconfirmed
  • Time Frame: Response assessed at the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years
    Safety Issue?: No
• Number of patients with overall survival
  • Time Frame: Patients will be followed for survival for 2 years from date of last patient off study, or death, whichever occurs first. Contacts will be every 4 months.
    Safety Issue?: No
• Time to disease progression, duration of response, and time to response
  • Time Frame: At the end of every 8 weeks from date of first dose treatment; every 12 weeks after 40 week assessment; at end of treatment visit until progressive disease. Duration is approximately 3 years.
    Safety Issue?: No
• Number of adverse events, serious adverse events, assessments of clinical laboratory values and clinically important abnormalities, and vital sign measurements
  • Time Frame: For each patient, from screening period to 30 days after last dose of study drug, approximately 1 year
    Safety Issue?: Yes
• Time to subsequent antineoplastic therapy
  • Time Frame: From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years
    Safety Issue?: No
• Plasma concentration-time data to contribute to future population pharmacokinetics (PK) analysis
  • Time Frame: Cycle 1, Days 1&7; Cycle 2, Day 8; Cycle 3, Day 8; Cycle 4, Day 8. Duration approximately 4 months.
    Safety Issue?: No
• Changes in reported symptoms and Quality of Life (QOL) assessment per Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) for functioning and symptoms
  • Time Frame: At screening period; Day 1 of each cycle; End of Treatment; Progression Free Survival follow-up. Duration approximately 3 years.
    Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria

• Male or female patients age 18 or older
• Patients with PTCL according to World Health Organization (WHO) criteria and have relapsed or are refractory to at least 1 prior systemic, cytoxic therapy for PTCL. Patients must have received conventional therapy as a prior therapy. Cutaneous-only disease is no permitted. Patients must have documented evidence of progressive disease.
• Tumor biopsy available for central hematopathologic review
• Measurable disease according to the IWG criteria
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Female patients 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 patients 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
• Patients 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
• Patients 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 patient must have recovered to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≤ 1 toxicity, to patients'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 patients 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

• Lead Sponsor
  • Millennium Pharmaceuticals, Inc.
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Medical Monitor, Study Director, Millennium Pharmaceuticals, Inc.
• Overall Contact(s)
  • For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center, 1-877-674-3784, medical@mlnm.com