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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Millennium Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01482962
First received: November 28, 2011
Last updated: July 23, 2013
Last verified: July 2013

November 28, 2011
July 23, 2013
June 2012
November 2016   (final data collection date for primary outcome measure)
  • 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
Same as current
Complete list of historical versions of study NCT01482962 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Alisertib (MLN8237) or Investigator's Choice in Patients With Relapsed/Refractory Peripheral T-Cell Lymphoma
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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Relapsed Peripheral T-Cell Lymphoma
  • Refractory Peripheral T-Cell Lymphoma
  • 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.

  • Experimental: Alisertib
    Alisertib
    Intervention: Drug: Alisertib
  • Active Comparator: Pralatrexate, or Romidepsin, or Gemcitabine
    Pralatrexate,or Romidepsin,or Gemcitabine
    Interventions:
    • Drug: Pralatrexate
    • Drug: Gemcitabine
    • Drug: Romidepsin
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
354
February 2017
November 2016   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact: For an updated listing of recruitment sites contact: Millennium Medical and Drug Information Center 1-877-674-3784 medical@mlnm.com
United States,   Canada
 
NCT01482962
C14012, 2011-003545-18
Yes
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
Not Provided
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals, Inc.
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP