Alisertib in Treating Patients With Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma
|ClinicalTrials.gov Identifier: NCT01466881|
Recruitment Status : Completed
First Posted : November 8, 2011
Results First Posted : March 10, 2016
Last Update Posted : March 10, 2016
|Condition or disease||Intervention/treatment||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|
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.
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||42 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of the Aurora Kinase A Inhibitor MLN8237, in Relapsed or Refractory Peripheral T-Cell Non-Hodgkin Lymphoma|
|Study Start Date :||October 2011|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||March 2015|
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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Objective Response Rate (Complete Responses (CR) + Partial Responses (PR)) [ Time Frame: Up to 1 year after registration ]Objective disease status is evaluated according to the 2007 revised Cheson et al. criteria. Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow (BM) must be negative if positive at baseline. Normalization of markers. Partial Response(PR) is a 50% decrease in the SPD for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.
- Overall Survival (OS) [ Time Frame: Up to 2 years after registration ]Measure from date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
- Progression Free Survival (PFS) [ Time Frame: Up to 2 years after registration ]Measured from date of registration to date of first observation of progressive disease or death due to any cause. Patients last known to be alive and without report of progressive disease are censored at date of last contact. Progressive disease is at least 50% increase in the sum of the product of the diameters (SPD) of target measurable nodal lesions over the smallest sum observed or ≥ 50% increase in the greatest transverse diameter (GTD) of any node > 1 cm in shortest axis, or ≥ 50% increase in the SPD of other target measurable lesions over the smallest sum observed. New bone marrow involvement. New lesion > 1.5 cm in longest axis, or ≥ 50% increase in GTD of any previously involved node with a diameter ≤ 1.0 cm in the short axis such that its longest axis is now > 1.5 cm. Lymph nodes with long axis is > 1.5 cm, or if the both the long and short axes are > 1 cm. PET should be positive if positive PET at baseline.
- To Evaluate the Safety and Tolerability of MLN8237 (Number of With Grade 3 Through Grade 5 Adverse Events That Are Related to MLN8237) [ Time Frame: Up to 1 year after registration ]Incidence of toxicity as assessed by the Common Terminology Criteria for Adverse Events version 4.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.
- Aurora Kinase A Expression [ Time Frame: Baseline ]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 PTCL treated with MLN8237
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01466881
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|Principal Investigator:||Paul Barr||Southwest Oncology Group|