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

NCT02776813 | Completed Phase 1 DMC

• 2 other identifiers: UT-201501ATTCK-20-2
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 7

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.

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (5)

• Safety as assessed by dose limiting toxicities (DLTs)

  28 days

• Safety as assessed by determination of the maximum tolerated dose (MTD)

  24 months

• Safety as assessed by determination of the recommended phase 2 dose (RP2D)

  24 months

• Safety as assessed by and adverse events, laboratory assessments and physical examinations

  24 months

• Safety as assessed by mini-mental state examination (MMSE)

  24 months

Secondary Outcomes (4)

• Overall response rate

  24 months

• Duration of response

  24 months

• Progression free survival

  24 months

• Overall survival

  60 months

Other Outcomes (4)

• ACRT087 persistence

  60 months

• Serum inflammatory markers

  169 days

• Serum cytokine levels

  169 days

Study Arms (1)

ACTR087, in combination with rituximab

EXPERIMENTAL

Biological: ACTR087; Biological: rituximab

Interventions

ACTR087 BIOLOGICAL

ACTR087, in combination with rituximab

rituximab BIOLOGICAL

ACTR087, in combination with rituximab

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Cogent Biosciences, Inc.: lead

Study Sites (7)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Loyola University Chicago

Maywood, Illinois, 60153, United States

Location

Indiana Bone and Marrow Transplantation

Indianapolis, Indiana, 46237, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Publications (1)

• 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.

  PMID: 34515338 DERIVED

MeSH Terms

Conditions

Lymphoma; Recurrence

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Jessica Sachs, MD

  Cogent Biosciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 4, 2016
• First Posted: May 18, 2016
• Study Start: August 1, 2016
• Primary Completion: February 12, 2020
• Study Completion: February 12, 2020
• Last Updated: March 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)