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

Sponsor

Cogent Biosciences, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02776813

Collaborator

(none)

Enrollment

Locations

Arm

42.4

Actual Duration (Months)

4.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

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

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 :

Aug 1, 2016

Actual Primary Completion Date :

Feb 12, 2020

Actual Study Completion Date :

Feb 12, 2020

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: ACTR087, in combination with rituximab

Biological: ACTR087

Biological: rituximab

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Overall response rate [24 months]
Duration of response [24 months]
Progression free survival [24 months]
Overall survival [60 months]

Other Outcome Measures

ACRT087 persistence [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 [169 days]
Serum cytokine levels [169 days]
Rituximab serum concentrations [147 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	Banner MD Anderson Cancer Center	Gilbert	Arizona	United States	85234
2	Yale University	New Haven	Connecticut	United States	06520
3	Loyola University Chicago	Maywood	Illinois	United States	60153
4	Indiana Bone and Marrow Transplantation	Indianapolis	Indiana	United States	46237
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Duke University Medical Center	Durham	North Carolina	United States	27710
7	Ohio State University	Columbus	Ohio	United States	43210