Clinical Trials /

Study of ACTR707 in Combination With Rituximab in Subjects With Relapsed or Refractory B Cell Lymphoma

NCT03189836

Description:

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety and anti-lymphoma activity of an autologous T cell product (ACTR707) in combination with rituximab in subjects with refractory or relapsed CD20+ B cell lymphoma.

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

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of ACTR707 in Combination With Rituximab in Subjects With Relapsed or Refractory B Cell Lymphoma
  • Official Title: Phase 1 Study of ACTR707, an Autologous T Cell Product, in Combination With Rituximab, in Subjects With Relapsed or Refractory CD20+ B Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: ATTCK-20-03
  • NCT ID: NCT03189836

Conditions

  • Lymphoma

Interventions

DrugSynonymsArms
ACTR707ACTR707 in combination with rituximab
rituximabACTR707 in combination with rituximab

Purpose

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety and anti-lymphoma activity of an autologous T cell product (ACTR707) in combination with rituximab in subjects with refractory or relapsed CD20+ B cell lymphoma.

Trial Arms

NameTypeDescriptionInterventions
ACTR707 in combination with rituximabExperimental
  • ACTR707
  • rituximab

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 (prior dx of FL before transforming to DLBCL).

          -  biopsy-confirmed CD20+ expression of the underlying malignancy with disease
             progression following immediate prior therapy

          -  at least 1 measurable lesion on imaging.

          -  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 polymerase
                  chain reaction (PCR): relapsed or refractory disease after at least 1 prior
                  regimen with chemo-immunotherapy (prior auto-HSCT is allowable)

          -  ECOG 0 or 1

          -  life expectancy of at least 6 months

          -  platelet count greater than 50,000/µL

        Exclusion Criteria:

          -  known active central nervous system (CNS) involvement by malignancy.

          -  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

          -  clinically significant cardiac disease

          -  clinically significant active infection

          -  clinically significant CNS disorder

          -  clinical history, prior diagnosis, or overt evidence of autoimmune disease

          -  known bone marrow involvement due to underlying malignant disease, in dose-escalation
             phase only
      
Maximum Eligible Age:80 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety as assessed by dose limiting toxicities (DLTs)
Time Frame:28 days
Safety Issue:
Description:Dose-limiting toxicities, MTD, incidence and severity of AEs and clinically significant abnormalities of laboratory values

Secondary Outcome Measures

Measure:Anti-lymphoma activity as measured by overall response rate
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Anti-lymphoma activity as measured by duration of response
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Anti-lymphoma activity as measured by progression-free survival
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Anti-lymphoma activity as measure by overall survival
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Assessment of persistence of ACTR707 as measured by flow cytometry and qPCR
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Assessment of ACTR707 phenotype and function as measured by flow cytometry
Time Frame:24 weeks
Safety Issue:
Description:
Measure:Assessment of inflammatory markers and cytokines/chemokines
Time Frame:24 weeks
Safety Issue:
Description:Cytokines and Inflammatory markers
Measure:Rituximab PK
Time Frame:24 weeks
Safety Issue:
Description:Rituximab plasma concentration

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Unum Therapeutics Inc.

Trial Keywords

  • CD20+
  • B cell
  • ACTR
  • ACTR707
  • relapsed
  • refractory
  • T cell
  • T cell product
  • adoptive T cells
  • gene therapy

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