Clinical Trials /

Study of ACTR087 in Subjects With Relapsed or Refractory B-cell Lymphoma

NCT02776813

Description:

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety and efficacy of an autologous T-cell product expressing ACTR in combination with rituximab in subjects with refractory or relapsed CD20+ B-cell lymphoma.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
  • Grade 3b Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Mediastinal Large B-Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title:Study of ACTR087 in Subjects With Relapsed or Refractory B-cell Lymphoma
  • Official Title:Phase 1 Study of ACTR087, Autologous T Lymphocytes Expressing Antibody Coupled T-cell Receptors (CD16V-41BB-CD3ζ), in Combination With Rituximab, in Subjects With Relapsed or Refractory CD20-Positive B-Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: UT-201501
  • NCT ID: NCT02776813

Trial Conditions

  • Lymphoma

Trial Interventions

DrugSynonymsArms

Trial Purpose

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety and efficacy of an autologous T-cell product expressing ACTR in combination with rituximab in subjects with refractory or relapsed CD20+ B-cell lymphoma.

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
ACTR087, in combination with rituximabExperimental

    Eligibility Criteria

    Inclusion Criteria:

    - Signed written informed consent obtained prior to study procedures

    - Histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy:

    - DLBCL, regardless of cell of origin or underlying molecular genetics

    - MCL

    - PMBCL

    - Gr3b-FL

    - TH-FL

    - Biopsy-confirmed CD20+ expression of the underlying malignancy by immunohistochemical staining or flow cytometry between the most recent dose of an anti-CD20 monoclonal antibody (mAb) and study enrollment

    - At least 1 measurable lesion on imaging. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy

    - Must have received adequate prior therapy for the underlying CD20+ B-cell lymphoma, defined as an anti-CD20 mAb in combination with an anthracycline-containing chemotherapy regimen (i.e. chemo-immunotherapy) and at least one of the following:

    - biopsy-proven refractory disease after frontline chemo-immunotherapy

    - relapse within 1 year from frontline chemo-immunotherapy and ineligible for autologous hematopoietic stem cell transplant (auto-HSCT)

    - For subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT

    - For subjects with TH-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT. At least 1 prior regimen with an anti-CD20 mAb in combination with chemotherapy is required following documented transformation

    - For subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)

    - Karnofsky performance scale ≥ 60%

    - Life expectancy of at least 6 months

    - ANC > 1000/µL

    - Platelet count > 50,000/µL

    - For women of childbearing potential (defined as physiologically capable of becoming pregnant), agreement to use of highly effective contraception for at least 1 year following ACTR087 infusion. For men with partners of childbearing potential, agreement to use effective barrier contraception for at least 1 year following ACTR087 infusion

    Exclusion Criteria:

    - Known active central nervous system (CNS) involvement by malignancy. Subjects with prior CNS involvement with their lymphoma must have completed effective treatment of their CNS disease at least 3 months prior to enrollment with no evidence of disease clinically and at least stable findings on relevant CNS imaging

    - Prior treatment as follows:

    - alemtuzumab within 6 months of enrollment

    - fludarabine, cladribine, or clofarabine within 3 months of enrollment

    - external beam radiation within 2 weeks of enrollment

    - mAb (including rituximab) within 2 weeks of enrollment

    - other lymphotoxic chemotherapy (including steroids except as below) within 2 weeks of enrollment

    - experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy

    - Serum creatinine ≥ 1.5 X age-adjusted upper limits of normal (ULN)

    - Pulse oximetry < 92% on room air

    - Direct bilirubin ≥ 3.0 mg/dL (50 mmol/L)

    - Alanine transaminase (ALT) ≥ 3 times the ULN, unless determined to be directly due to lymphoma.

    - Aspartate transaminase (AST) ≥ 3 times the ULN, unless determined to be directly due to lymphoma

    - Class III or IV heart failure as defined by the New York Heart Association (NYHA), history of cardiac angioplasty or stenting, documented myocardial infarction or unstable angina within 6 months prior to enrollment, cardiac ejection fraction of < 45%, or other clinically significant cardiac disease

    - Clinical history of, prior diagnosis of, or overt evidence of autoimmune disease, regardless of severity

    - Clinically significant active infection, in the judgment of the investigator

    - Pregnancy (negative serum pregnancy test to be obtained within 6 days prior to enrollment for subjects of childbearing potential)

    - Breastfeeding

    - Primary immunodeficiency

    - Seropositive for Human Immunodeficiency Virus (HIV) 1 or HIV 2, or positive hepatitis B surface antigen (HBsAg) or hepatitis C antibody

    - Will need or has needed active treatment of a second malignancy within the prior 3 years before enrollment, other than FL, non-melanoma skin cancers, localized prostate cancer treated with curative intent, or cervical carcinoma in situ

    - Is unable to receive any of the agents used in this study due a history of severe immediate hypersensitivity reaction (e.g. hypersensitivity to dimethyl sulfoxide (DMSO))

    - History of prior allogeneic HSCT

    - History of Richter's transformation from CLL

    - Prior infusion of a genetically modified therapy

    Maximum Eligible Age:75 Years
    Minimum Eligible Age:18 Years
    Eligible Gender:Both
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Safety as assessed by dose limiting toxicities (DLTs)
    Time Frame:28 days
    Safety Issue:Yes
    Description:

    Secondary Outcome Measures

    Measure:Overall response rate
    Time Frame:24 months
    Safety Issue:No
    Description:
    Measure:Duration of response
    Time Frame:24 months
    Safety Issue:No
    Description:
    Measure:Progression free survival
    Time Frame:24 months
    Safety Issue:No
    Description:
    Measure:Overall survival
    Time Frame:60 months
    Safety Issue:No
    Description:

    Trial Keywords

    • CD20+
    • B-cell
    • ACTR087
    • Relapsed
    • Refractory