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

• ClinicalTrials.gov Identifier: NCT02776813
• Recruitment Status: Completed
• First Posted: May 18, 2016
• Last Update Posted: March 31, 2020
• Sponsor: Cogent Biosciences, Inc.
• Information provided by (Responsible Party): Cogent Biosciences, Inc.

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Lymphoma	Biological: ACTR087; Biological: rituximab	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• 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
• Actual Study Start Date: August 2016
• Actual Primary Completion Date: February 12, 2020
• Actual Study Completion Date: February 12, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: ACTR087, in combination with rituximab	Biological: ACTR087; Biological: rituximab

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Overall response rate [ Time Frame: 24 months ]
2. Duration of response [ Time Frame: 24 months ]
3. Progression free survival [ Time Frame: 24 months ]
4. Overall survival [ Time Frame: 60 months ]

Other Outcome Measures:

1. 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
2. Serum inflammatory markers [ Time Frame: 169 days ]
3. Serum cytokine levels [ Time Frame: 169 days ]
4. Rituximab serum concentrations [ Time Frame: 147 days ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• 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

Locations

United States, Arizona

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

United States, Connecticut

Yale University

New Haven, Connecticut, United States, 06520

United States, Illinois

Loyola University Chicago

Maywood, Illinois, United States, 60153

United States, Indiana

Indiana Bone and Marrow Transplantation

Indianapolis, Indiana, United States, 46237

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, Ohio

Ohio State University

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

Cogent Biosciences, Inc.

Investigators

• Study Director: Jessica Sachs, MD; Cogent Biosciences, Inc.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

• Responsible Party: Cogent Biosciences, Inc.
• ClinicalTrials.gov Identifier: NCT02776813
• Other Study ID Numbers: UT-201501; ATTCK-20-2 ( Other Identifier: Unum Therapeutics )
• First Posted: May 18, 2016
• Last Update Posted: March 31, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Cogent Biosciences, Inc.:

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

Additional relevant MeSH terms:

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Rituximab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents