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

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Unum Therapeutics Inc.
Sponsor:
Information provided by (Responsible Party):
Unum Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT02776813
First received: May 4, 2016
Last updated: February 13, 2017
Last verified: February 2017
  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.

Condition Intervention Phase
Lymphoma Biological: ACTR087 Biological: rituximab Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Unum Therapeutics Inc.:

Primary Outcome Measures:
  • Safety as assessed by dose limiting toxicities (DLTs) [ Time Frame: 28 days ]
  • Safety as assessed by determination of the maximum tolerated dose (MTD) [ Time Frame: 24 months ]
  • Safety as assessed by determination of the recommended phase 2 dose (RP2D) [ Time Frame: 24 months ]
  • Safety as assessed by and adverse events, laboratory assessments and physical examinations [ Time Frame: 24 months ]
  • Safety as assessed by mini-mental state examination (MMSE) [ Time Frame: 24 months ]

Secondary Outcome Measures:
  • Overall response rate [ Time Frame: 24 months ]
  • Duration of response [ Time Frame: 24 months ]
  • Progression free survival [ Time Frame: 24 months ]
  • Overall survival [ Time Frame: 60 months ]

Other Outcome Measures:
  • ACRT087 persistence [ Time Frame: 60 months ]
    Blood samples will be collected and analyzed for the presence of T-cells which express antibody coupled T-cell receptors, using flow cytometry and qPCR

  • Serum inflammatory markers [ Time Frame: 169 days ]
  • Serum cytokine levels [ Time Frame: 169 days ]
  • Rituximab serum concentrations [ Time Frame: 147 days ]

Estimated Enrollment: 54
Study Start Date: August 2016
Estimated Study Completion Date: March 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ACTR087, in combination with rituximab Biological: ACTR087 Biological: rituximab

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02776813

Contacts
Contact: Michael O'Meara (617) 453 8344 michael.omeara@unumrx.com
Contact: Michael Vasconcelles, MD (857) 209 4741 michael.vasconcelles@unumrx.com

Locations
United States, Indiana
Indiana Bone and Marrow Transplantation Recruiting
Indianapolis, Indiana, United States, 46237
Contact: Luke P Akard, MD    317-528-5500      
Contact: Lorraine "Kay" Harvey, BSN RN CCRN CCRP    317-528-5500    lorraine.harvey@franciscanalliance.org   
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jeremy Abramson, MD    617-724-4000    jabramson@mgh.harvard.edu   
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Bonnie Toaso, RN    919-681-4769    bonnie.toaso@duke.edu   
Contact: Peggy Alton    919 684 9220    peggy.alton@duke.edu   
Principal Investigator: Anne Beaven, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Samantha M Jaglowski, MD    614-293-3316    samantha.jaglowski@osumc.edu   
Contact: Steven M Devine, MD    614-293-3316    steven.devine@osumc.edu   
Sponsors and Collaborators
Unum Therapeutics Inc.
Investigators
Study Director: Michael Vasconcelles, MD Unum Therapeutics Inc.
  More Information

Responsible Party: Unum Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT02776813     History of Changes
Other Study ID Numbers: UT-201501
ATTCK-20-2 ( Other Identifier: Unum Therapeutics )
Study First Received: May 4, 2016
Last Updated: February 13, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Unum Therapeutics Inc.:
CD20+
B-cell
ACTR087
Relapsed
Refractory

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 26, 2017