This phase II trial studies how well onalespib works in treating patients with anaplastic large cell lymphoma, mantle cell lymphoma, or diffuse large B-cell lymphoma that has not responded to previous treatment (refractory) or that has returned after a period of improvement (recurrent). Onalespib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVE: I. Overall response rate (ORR) to single agent AT13387 (onalespib) as measured by the proportion of partial and complete responses (PR + CR) in patients with relapsed/refractory ALK positive (+) anaplastic large cell lymphoma (ALCL), mantle cell lymphoma (MCL), and BCL6+ diffuse large B cell lymphoma (DLBCL). SECONDARY OBJECTIVES: I. Progression free survival (PFS) and overall survival (OS), as well as duration of response (DOR) of single agent AT13387 (onalespib) in patients with ALK+ ALCL, MCL, and BCL6+ DLBCL. II. Safety and tolerability of single agent AT13387 (onalespib) in patients with ALK+ ALCL, MCL, and BCL6+ DLBCL. EXPLORATORY OBJECTIVES: I. Measurement of on-target activity of AT13387 (onalespib) in ALK+ ALCL, MCL, and BCL6+ DLBCL through immunoblotting and immunohistochemistry of pre-treatment, on-treatment, and time of progression tumor biopsies for HSP90 clients. II. Determination of genetic and transcriptional markers for response and resistance to AT13387 (onalespib) in patients with ALK+ ALCL, MCL, and BCL6+ DLBCL. OUTLINE: Patients receive onalespib intravenously (IV) over 1 hour on days 1, 2, 8, 9, 15, and 16. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6 months for up to 1 year.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Given IV
Los Angeles County-USC Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
USC Norris Oncology/Hematology-Newport Beach
Newport Beach, California, United States
Keck Medical Center of USC Pasadena
Pasadena, California, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, United States
Brigham and Women's Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Nebraska Medicine-Bellevue
Bellevue, Nebraska, United States
Nebraska Medicine-Village Pointe
Omaha, Nebraska, United States
...and 9 more locations
Objective Response Rate
Objective response (OR) = Complete + Partial (CR + PR) Per International Harmonization Project for lymphoma criteria, CR is defined as the disappearance of all evidence of disease. For FDG-avid or PET positive sites of disease prior to therapy, a mass of any size is permitted if PET negative; for variably FDG avid or PET negative lesions, regression to normal size on CT is necessary. The spleen or liver must also be nonpalpable with disappearance of any nodules, and the bone marrow, if initially involved, must be cleared on repeat biopsy. PR is defined as regression of measurable disease and no new sites of disease: a \>50% decrease in the sum of the diameters of the up to 6 largest dominant masses with no increase in size of other masses. If the sites of disease were PET positive at baseline, there must be at least one previously involved site that remains PET positive.
Time frame: Assessed every 2 cycles during treatment until disease progression; patients who discontinue for reasons other than progression will be evaluated every 6 months for up to 1 year after ending treatment or until progression or next therapy
Frequency of Toxicities
Will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (version 5.0 is used staring April 1, 2018). Toxicities will be summarized with counts and proportions within each cohort and overall.
Time frame: Assessed days 1, 2, 8, 9, 15, 16 of each 28-day cycle during treatment until progression; patients who discontinue for reasons other than progression evaluated every 6 months for up to 1 year after ending treatment or until progression or next therapy
Progression-free Survival
The progression-free survival will be estimated by Kaplan-Meier method. Progressive disease is defined by the International Harmonization Project for lymphoma criteria: any new lesion or an increase by \> 50% of previously involved sites from nadir. This includes the appearance of any new lesion(s) \> 1.5cm in any axis, a \> 50% increase in the sum of diameters of \> 1 site of disease or \> 50% increase in the longest diameter of a previously identified node \>1cm in short axis. If the sites of disease were PET positive at baseline, they must remain PET positive.
Time frame: From the date of study entry until documentation of first progression or death from any cause; progression assessed every 2 cycles during treatment until disease progression or death
Overall Survival
The overall survival will be estimated by Kaplan-Meier method. Median follow-up time will be assessed using the reverse Kaplan-Meier method.
Time frame: From the date of study entry until death from any cause; assessed every 6 months for up to 1 year after ending treatment
Duration of Response
Duration of response will be evaluated only in patients who respond with either a partial response or complete response while on study.
Time frame: From first objective response (partial response or complete response) until the first date of documented progression assessed every 2 cycles or death due to any cause; assessed every 6 months up to 1 year after ending treatment
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