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

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc. Identifier:
First received: November 28, 2011
Last updated: February 25, 2015
Last verified: February 2015

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.

Condition Intervention Phase
Relapsed Peripheral T-Cell Lymphoma
Refractory Peripheral T-Cell Lymphoma
Drug: Alisertib
Drug: Pralatrexate
Drug: Gemcitabine
Drug: Romidepsin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome 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 ] [ Designated as safety issue: No ]
    Overall response rate (ORR) by central review + progression free survival (PFS)

  • 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 ] [ Designated as safety issue: No ]
    Based on IRC assessment using a modified IWG (2007) criteria

Secondary Outcome 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 ] [ Designated as 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. ] [ Designated as 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. ] [ Designated as 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 ] [ Designated as safety issue: Yes ]
    Safety and tolerability of alisertib

  • Time to subsequent antineoplastic therapy [ Time Frame: From date of last study drug to date of subsequent antineoplastic therapy, if required; approximately 3 years ] [ Designated as 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. ] [ Designated as 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. ] [ Designated as safety issue: No ]

Enrollment: 271
Study Start Date: June 2012
Estimated Study Completion Date: February 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Alisertib
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.
Active Comparator: Pralatrexate, or Romidepsin, or Gemcitabine
Pralatrexate,or Romidepsin,or Gemcitabine
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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01482962

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United States, Alabama
Birmingham, Alabama, United States
United States, California
La Jolla, California, United States
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Orlando, Florida, United States
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Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Millennium Pharmaceuticals, Inc. Identifier: NCT01482962     History of Changes
Other Study ID Numbers: C14012, 2011-003545-18, DRKS00004503, NL39566.068.12
Study First Received: November 28, 2011
Last Updated: February 25, 2015
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Ministry of Health

Additional relevant MeSH terms:
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms by Histologic Type
Anti-Infective Agents
Antibiotics, Antineoplastic
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses processed this record on March 03, 2015