Phase 2 Study of AT13387 (Onalespib) in ALK+ ALCL, MCL, and BCL-6+ DLBCL

NCT02572453 | Terminated Phase 2 Results DMC

• 5 other identifiers: NCI-2015-0168116-7129875UM1CA186690UM1CA186709
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 19

Brief Summary

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.

Conditions

Recurrent Anaplastic Large Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Transformed Non-Hodgkin Lymphoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Refractory Transformed Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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

Secondary Outcomes (4)

• Frequency of Toxicities

  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

  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

  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

  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

Other Outcomes (5)

• Change in Protein Levels of BCL6 in Diffuse Large B Cell Lymphoma

  Assessed days 1, 8, 15 of each 28-day cycle and at treatment completion visit

• Change in Protein Levels of Cyclin D1 in Mantle Cell Lymphoma

  Assessed days 1, 8, 15 of each 28-day cycle and at treatment completion visit

• Change in Protein Levels of ALK in ALK+ Anaplastic Large Cell Lymphoma

  Assessed days 1, 8, 15 of each 28-day cycle and at treatment completion visit

Study Arms (3)

ALK+ ALCL

EXPERIMENTAL

Patients receive 160-mg/m2 onalespib by IV over 1 hour on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Patients will continue on treatment indefinitely as long as they are responding and tolerating treatment.

Drug: Onalespib

Relapsed MCL

EXPERIMENTAL

Patients receive 160-mg/m2 onalespib by IV over 1 hour on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Patients will continue on treatment indefinitely as long as they are responding and tolerating treatment.

Drug: Onalespib

BCL6+ DLBCL

EXPERIMENTAL

Patients receive 160-mg/m2 onalespib by IV over 1 hour on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. Patients will continue on treatment indefinitely as long as they are responding and tolerating treatment.

Drug: Onalespib

Interventions

Onalespib DRUG

Given IV

Also known as: AT 13387, AT-13387, AT13387

ALK+ ALCL; BCL6+ DLBCL; Relapsed MCL

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed, relapsed/refractory ALK+ ALCL (with ALK positivity defined by immunohistochemistry and/or fluorescence in situ hybridization \[FISH\]/cytogenetics from any prior biopsy), MCL, or BCL6+ DLBCL (with BCL6 positivity defined by immunohistochemistry from any prior biopsy) and meet the following criteria:
• Patients must have measurable disease that has not been previously irradiated, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as \>= 20 mm (\>= 2 cm) with conventional imaging or \>= 10 mm with spiral computed tomography (CT) scan; if the patient has been previously irradiated, there must be evidence of progression since the radiation
• Please note, this trial includes mandatory tumor biopsies pre-treatment, during cycle 1 and at the time of disease progression of accessible tumor; having accessible tumor for biopsy is not required for eligibility; we expect that at least 80% of patients will have accessible tumor for these biopsies, however
• Prior therapy
• Please note, the washout period for prior therapies cannot be shortened
• Please note, prior therapies can be from any time in the past
• ALK+ ALCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included a multiagent chemotherapy regimen including an anthracycline, if not contraindicated, and prior brentuximab; prior crizotinib or other ALK inhibitor therapy, while recommended, is not mandatory; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
• MCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included a multiagent chemotherapy regimen and prior ibrutinib or other BTK inhibitor therapy; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
• BCL6+ DLBCL: patients must have disease that has relapsed and or is refractory to prior therapy, which must have included an anthracycline, if not contraindicated; patients must have relapsed following or be ineligible for, or refuse, autologous stem cell transplant
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 3 months
• Absolute neutrophil count \>= 1,000/mcL
• Platelets \>= 75,000/mcL, unless due to marrow involvement by lymphoma in which case a platelet count of \>= 30,000/mcL will be used
• Total bilirubin =\< 1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome or hemolysis, in which case =\< 3.0 x ULN is allowed
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 3.0 x institutional upper limit of normal

You may not qualify if:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier; steroids for symptom palliation are allowed, but must be either discontinued or on stable doses at the time of initiation of protocol therapy
• Patients who are receiving any other investigational agents; all investigational agents other than ibrutinib must have been discontinued at least 4 weeks prior to beginning treatment; prior ibrutinib therapy must have been discontinued at least 2 weeks prior to beginning therapy
• Patients with known leptomeningeal or brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events; imaging or spinal fluid analysis to exclude central nervous system (CNS) involvement is not required, unless there is clinical suspicion by the treating investigator
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to AT13387 (onalespib)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study because AT13387 (onalespib) has the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with AT13387 (onalespib), breastfeeding should be discontinued if the mother is treated with AT13387 (onalespib)
• Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
• Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least three years; patients with prostate cancer are allowed if prostate specific antigen (PSA) is less than 1
• Patients should not receive immunization with attenuated live vaccine within one week of study entry or during study period
• History of noncompliance to medical regimens
• Consistent corrected QT (QTc) \> 450 msec for men and \> 470 msec for women by Fridericia formula, on 3 separate electrocardiograms (ECGs)
• Left ventricular ejection fraction (LVEF) \< 50%, regardless of whether there are symptoms of heart failure

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (19)

Los Angeles County-USC Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Oncology/Hematology-Newport Beach

Newport Beach, California, 92663, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Nebraska Medicine-Bellevue

Bellevue, Nebraska, 68123, United States

Location

Nebraska Medicine-Village Pointe

Omaha, Nebraska, 68118, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, 08903, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Parkland Memorial Hospital

Dallas, Texas, 75235, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, Anaplastic; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell

Interventions

(2,4-dihydroxy-5-isopropylphenyl)-(5-(4-methylpiperazin-1-ylmethyl)-1,3-dihydroisoindol-2-yl)methanone

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Results Point of Contact

• Title: Jillian Foreman
• Organization: Dana-Farber Cancer Institute

jillianM_foreman@dfci.harvard.edu

1-877-338-7425

Study Officials

• Caron A Jacobson

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Patients are enrolled onto one of three parallel, non-comparative arms by disease type; treatment regimens are the same for each arm.

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: October 9, 2015
• Study Start: April 4, 2016
• Primary Completion: March 18, 2021
• Study Completion: March 18, 2021
• Last Updated: September 13, 2022
• Results First Posted: September 13, 2022

Record last verified: 2022-08

Locations

US (19)