Clinical Trials /

Onalespib in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-Cell Lymphoma

NCT02572453

Description:

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 or that has returned after a period of improvement. Onalespib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Onalespib in Treating Patients With Relapsed or Refractory Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma, or Diffuse Large B-Cell Lymphoma
  • Official Title: Phase 2 Study of AT13387 (Onalespib) in ALK+ ALCL, MCL, and BCL-6+ DLBCL

Clinical Trial IDs

  • ORG STUDY ID: NCI-2015-01681
  • SECONDARY ID: NCI-2015-01681
  • SECONDARY ID: 15-XXX
  • SECONDARY ID: 16-712
  • SECONDARY ID: 9875
  • SECONDARY ID: 9875
  • SECONDARY ID: UM1CA186690
  • SECONDARY ID: UM1CA186709
  • NCT ID: NCT02572453

Conditions

  • ALK Positive
  • BCL6 Positive
  • Recurrent Anaplastic Large Cell Lymphoma
  • Recurrent Diffuse Large B-Cell Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Refractory Anaplastic Large Cell Lymphoma
  • Refractory Diffuse Large B-Cell Lymphoma
  • Refractory Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
OnalespibAT 13387, AT-13387, AT13387Treatment (onalespib)

Purpose

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 or that has returned after a period of improvement. Onalespib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      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.

      TERTIARY 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.
      Courses 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (onalespib)ExperimentalPatients receive onalespib IV over 1 hour on days 1, 2, 8, 9, 15, and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
  • Onalespib

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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

          -  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

          -  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

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  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; 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

          -  Pregnant women are excluded from this study; 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective response rate
Time Frame:Up to 1 year after completion of study treatment
Safety Issue:
Description:Will be evaluated using the International Harmonization Project for lymphoma criteria.

Secondary Outcome Measures

Measure:Incidence of toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 1 year after completion of study treatment
Safety Issue:
Description:Toxicities will be summarized with counts and proportions within each cohort and overall.
Measure:Progression free survival
Time Frame:From the date of study entry until documentation of first progression or death from any cause, assessed up to 1 year after completion of study treatment
Safety Issue:
Description:The progression free survival will be estimated by Kaplan-Meier method. Median follow-up time will be assessed using the reverse Kaplan-Meier method.
Measure:Overall survival
Time Frame:From the date of study entry until the date of death by any cause, assessed up to 1 year after completion of study treatment
Safety Issue:
Description:The overall survival will be estimated by Kaplan-Meier method. Median follow-up time will be assessed using the reverse Kaplan-Meier method.
Measure:Duration of response
Time Frame:From first objective response (partial response or complete response) until the first date of documented progression or death due to any cause, assessed up to 1 year after completion of study treatment
Safety Issue:
Description:Duration of response will be evaluated only in patients who respond with either a partial response or complete response while on study.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

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