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

Phase 1

Completed

• Conditions: Lymphoma
• Interventions: Biological: ACTR087; Biological: rituximab

• Registration Number: NCT02776813
• Lead Sponsor: Cogent Biosciences, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-05-04
• Study First Submitted QC: 2016-05-16
• Study First Posted: 2016-05-18
• Study Start: 2016-08
• Primary Completion: 2020-02-12
• Study Completion: 2020-02-12
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-27
• Last Update Posted: 2020-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ACTR087, in combination with rituximab	ACTR087	-
ACTR087, in combination with rituximab	rituximab	-

Primary Outcome Measures

Name	Time	Method
Safety as assessed by and adverse events, laboratory assessments and physical examinations	24 months
Safety as assessed by determination of the recommended phase 2 dose (RP2D)	24 months
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 mini-mental state examination (MMSE)	24 months

Secondary Outcome Measures

Name	Time	Method
Overall response rate	24 months
Duration of response	24 months
Overall survival	60 months
Progression free survival	24 months

Trial Locations

Locations (7)

Banner MD Anderson Cancer Center; 🇺🇸 Gilbert, Arizona, United States

Loyola University Chicago; 🇺🇸 Maywood, Illinois, United States

Indiana Bone and Marrow Transplantation; 🇺🇸 Indianapolis, Indiana, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States