Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01466881
First received: November 3, 2011
Last updated: May 6, 2015
Last verified: January 2015
  Purpose

This phase II trial studies how well alisertib works in treating patients with peripheral T-cell non-Hodgkin lymphoma that has come back after a period of improvement or has not responded to treatment. Alisertib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Condition Intervention Phase
Adult Nasal Type Extranodal NK/T-Cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-Cell Lymphoma
Hepatosplenic T-Cell Lymphoma
Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
Recurrent Adult Non-Hodgkin Lymphoma
Recurrent Adult T-Cell Leukemia/Lymphoma
Drug: Alisertib
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Trial of the Aurora Kinase A Inhibitor MLN8237, in Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Aurora kinase A expression [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Baseline expression levels of Aurora kinase A will be quantitated, ranked, and analyzed for association with overall response using univariate logistic regression.

  • Overall response rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Association between pre-treatment Aurora kinase A expression levels and overall response will be explored.


Secondary Outcome Measures:
  • Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 2 years ] [ Designated as safety issue: Yes ]
    Analyses will explore associations with Aurora kinase A expression levels.

  • OS [ Time Frame: From date of registration to date of death due to any cause, assessed at 1 year ] [ Designated as safety issue: No ]
    Analyses will explore associations with Aurora kinase A expression levels using univariate Cox regression.

  • PFS [ Time Frame: From date of registration to date of first observation of progressive disease or death due to any cause, assessed at 1 year ] [ Designated as safety issue: No ]
    Analyses will explore associations with Aurora kinase A expression levels using univariate Cox regression.


Estimated Enrollment: 39
Study Start Date: October 2011
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (alisertib)
Patients receive alisertib PO BID on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.
Drug: Alisertib
Given PO
Other Names:
  • ALISERTIB
  • Aurora A Kinase Inhibitor MLN8237
  • MLN-8237
  • MLN8237
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To estimate the objective response rate (complete responses + partial responses) after treatment with alisertib (MLN8237) in patients with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma.

II. To assess overall survival (OS) and progression-free survival (PFS) in this patient population.

III. To evaluate the safety and tolerability of MLN8237 treatment for this patient population.

IV. To explore the association between pre-treatment aurora kinase A expression in tumor biopsies as measured by fluorescence in situ hybridization (FISH) and objective response rate in patients with peripheral T-cell lymphomas (PTCL) treated with MLN8237.

IV. To investigate the copy number, mutational status, expression of aurora kinase (A, B, and C) and associated signaling pathways in PTCL utilizing tissue microarray analysis (TMA) before and after treatment with MLN8237.

V. To investigate changes in the serum cytokine profile pre- and post- aurora kinase Inhibitor treatment.

VI. To evaluate serum markers of apoptosis pre- and post- aurora kinase inhibitor treatment as pharmacodynamic markers of efficacy.

OUTLINE:

Patients receive alisertib orally (PO) twice daily (BID) on days 1-7. Treatment repeats every 21 days for 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 4 months for 2 years.

  Eligibility

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

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed relapsed/refractory non-Hodgkin lymphoma (NHL) having progressed after a minimum of one systemic therapy with any of the following T-cell histologies:

    • Peripheral T-cell NHL (PTCL) not otherwise specified (NOS)
    • Anaplastic large cell T-cell lymphoma (ALCL) that is anaplastic lymphoma kinase either positive or negative
    • Angioimmunoblastic T-cell NHL
    • Subcutaneous panniculitis-like T-cell lymphoma
    • Enteropathy-associated T-cell NHL
    • Hepatosplenic T-cell lymphomas
    • Extranodal natural killer (NK)/T-cell lymphoma, nasal type
    • Adult T-cell leukemia/lymphoma
    • Unclassifiable PTCL
    • Transformed cutaneous T-cell lymphoma (CTCL) to PTCL with systemic involvement (not local skin transformation)
    • No other histologies are eligible; examples of ineligible histologies include: T-cell prolymphocytic leukemia, T-cell large granular lymphocytic leukemia, NK-cell leukemia, mycosis fungoides, Sezary syndrome, lymphomatoid papulosis, and primary CTCL
  • Patients must have received at least one course of prior systemic therapy which may include chemotherapy, antibody therapy, or immunotherapy; for all forms of systemic therapy, patients must have completed therapy at least 21 days prior to registration; patients must not be within 84 days of radioimmunotherapy; steroids at a low dose for control of itching (up to the equivalent of 20 mg of prednisone daily) are allowed
  • Patients may have received prior radiation in combination with systemic therapy; patients must not be within 21 days of external beam radiation therapy
  • Patients must not have received a previous allogeneic stem cell transplant or be within 90 days of an autologous stem cell transplant
  • Adequate sections and a paraffin block from the relapsed/refractory specimen must be submitted for review by the lymphoma pathology group; an adequate biopsy requires sufficient tissue to establish the architecture and a Revised European American Lymphoma (REAL) or World Health Organization (WHO) histologic subtype with certainty; thus, core biopsies, especially multiple core biopsies MAY be adequate; whereas, needle aspirations or cytologies are not adequate
  • Patients must have bidimensionally measurable disease within 28 days prior to registration; a diagnostic quality computed tomography (CT) scan of the chest abdomen, pelvis, neck and positron emission tomography (PET)/CT must be performed within 28 days of registration (PET/CT scan can be done instead of separate PET and CT scans only if the CT component is a diagnostic CT with contrast); patients who also have non-measurable disease in addition to measurable disease must have all non-measurable disease assessed within 42 days prior to registration
  • Patients must have a bilateral or unilateral bone marrow aspirate and biopsy performed within 42 days prior to registration
  • Patients must not have clinical evidence of central nervous system involvement by lymphoma; any laboratory tests that are performed to assess clinical signs of central nervous system involvement must have been performed within 42 days prior to registration, and the results must be negative
  • Patients must be able to swallow tablets
  • Patients known to be human immunodeficiency virus (HIV)-positive must not have multi-drug resistant HIV infection, CD4 counts < 150/mcL, or other concurrent acquired immunodeficiency syndrome (AIDS)-defining conditions
  • Patients must be offered the opportunity to consent to the banking of specimens for future use
  • Absolute granulocyte count >= 1,500 cells/mcL; patients with documented marrow involvement may be transfused to this value
  • Platelet count >= 75,000 cells/mcL; patients with documented marrow involvement may be transfused to this value
  • Serum creatinine (mg/dL) =< institutional upper limit of normal (IULN) obtained within 14 days prior to registration
  • Calculated creatinine clearance > 50 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to registration
  • Serum bilirubin =< 2 times institutional upper limit of normal
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both =< 2.5 x IULN
  • Serum lactate dehydrogenase (LDH) obtained within 14 days prior to registration
  • Patients must have a Zubrod performance status of 0, 1, or 2
  • Patients must NOT have New York Heart Association (NYHA) class II-IV heart failure
  • No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for five years
  • Pregnant or nursing women are not eligible; women/men of reproductive potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for 4 months after completion of MLN8237 administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately
  • All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines
  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 ClinicalTrials.gov identifier: NCT01466881

  Show 162 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Paul Barr Southwest Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01466881     History of Changes
Other Study ID Numbers: NCI-2011-03551, NCI-2011-03551, SWOG-S1108, CDR0000714328, S1108, S1108, U10CA180888, U10CA032102
Study First Received: November 3, 2011
Last Updated: May 6, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immunoblastic Lymphadenopathy
Leukemia, T-Cell
Immune System Diseases
Immunoproliferative Disorders
Leukemia
Leukemia, Lymphoid
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on May 21, 2015