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Recurrent Anaplastic Large Cell LymphomaPhase 2NCT02572453

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

A Phase 2 study testing Onalespib in people with Recurrent Anaplastic Large Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 19 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Onalespib
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
19 sitesUnited States
Study dates
4 Apr 2016to 18 Mar 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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
  • Creatinine =< 1.5 x ULN or a creatinine clearance >= 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal
  • Potassium above the institutional lower limit of normal (supplementation to meet this is allowed)
  • Magnesium above the institutional lower limit of normal (supplementation to meet this is allowed)
  • Human immunodeficiency virus (HIV)+ patients are eligible for the trial provided they meet the other study criteria in addition to the following:
  • CD4+ T-cells >= 250/mm^3
  • HIV sensitive to antiretroviral therapy
  • Zidovudine not allowed
  • Long term survival anticipated on the basis of HIV alone were it not for the lymphoma
  • No concurrent acquired immunodeficiency syndrome (AIDS)-defining illness other than the lymphoma
  • The effects of AT13387 (onalespib) on the developing human fetus are unknown; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after the completion of AT13387 (onalespib) administration; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of AT13387 (onalespib) administration
  • Although the pharmacokinetic (PK) data in humans is still unknown, the potential for drug-interaction cannot be ruled out; pre-clinical studies suggest that AT13387 (onalespib) is a substrate of P-glycoprotein (P-gp), a moderate inhibitor of BCRP and P-gp, and a strong inhibitor of MATE 1/2-K; patients must be willing to not take St. John wort or grapefruit juice while participating in this trial and should avoid drugs that are strong inducers of P-gp, and to switch to alternative drugs when available
  • Hepatitis B positive patients are eligible; prophylactic hepatitis B virus (HBV) therapy is recommended but only if there is no circulating virus detectible
  • Transformed lymphoma patients are eligible
  • Ability to understand and the willingness to sign a written informed consent document

Who cannot join

  • 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
  • There will be no exclusion of patients with known visual impairment or symptoms, including by not limited to peripheral flashes (photopsia), blurred or double vision, floaters, color distortion and dimness, difficulties with light/dark accommodation, tunnel vision or other field defects, halos, apparent movement of stationary objects, and complex disturbances; patients will have a baseline ophthalmologic exam to serve as a point of comparison and further exams as needed should visual symptoms develop; no pretreatment eye exam findings or ocular symptoms have been associated with an increased risk of ocular toxicity seen with AT13387
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  • 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

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Nebraska Medicine-Bellevue

    Bellevue, Nebraska, 68123

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Los Angeles County-USC Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

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

    New Brunswick, New Jersey, 08903

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • USC Norris Oncology/Hematology-Newport Beach

    Newport Beach, California, 92663

  • Nebraska Medicine-Village Pointe

    Omaha, Nebraska, 68118

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Keck Medical Center of USC Pasadena

    Pasadena, California, 91105

  • University of Pittsburgh Cancer Institute (UPCI)

    Pittsburgh, Pennsylvania, 15232

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

About this study

Official title: Phase 2 Trial of the Heat Shock Protein-90 (Hsp90) Inhibitor AT13387 (Onalespib) in Patients With Relapsed/Refractory ALK+ ALCL, Mantle Cell Lymphoma, and BCL6+ DLBCL

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

Being tested
Onalespib
Medical subject headings
Lymphoma, Large-Cell, Anaplastic, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OnalespibDrug

    Also called AT 13387, AT-13387, AT13387

    Given IV

Study groups in NCT02572453
Study groupRoleWhat they receive
ALK+ ALCLExperimentalPatients 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.
Receives: Drug: Onalespib
Relapsed MCLExperimentalPatients 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.
Receives: Drug: Onalespib
BCL6+ DLBCLExperimentalPatients 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.
Receives: Drug: Onalespib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: From the date of study entry until death from any cause; assessed every 6 months for up to 1 year after ending treatment

  4. 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.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2015 (estimated)
  2. Study start4 Apr 2016
  3. Primary completion18 Mar 2021
  4. Study completion18 Mar 2021

Why it stopped: Drug supply issues

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Patients are enrolled onto one of three parallel, non-comparative arms by disease type; treatment regimens are the same for each arm.
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02572453
Sponsor's protocol ID
NCI-2015-01681
Other IDs
NCI-2015-01681, 16-712, 9875, 9875, UM1CA186690, UM1CA186709
Status last verified
Aug 2022
First submitted
8 Oct 2015
Last updated
13 Sep 2022
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Onalespib in people with Recurrent Anaplastic Large Cell Lymphoma and Recurrent Diffuse Large B-Cell Lymphoma, run by National Cancer Institute (NCI) at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective Response Rate (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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02572453.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2022.

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