Study of ACTR087 in Combination With SEA-BCMA in Subjects With Relapsed or Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title:

A Phase 1 Study of ACTR087, an Autologous T Cell Product, in Combination With SEA-BCMA, a Monoclonal Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03266692
• Other study ID #: ATTCK-17-01
• Status: Terminated
• Phase: Phase 1
• Start date: February 22, 2018
• Est. completion date: October 1, 2019

Study information

• Verified date: March 2020
• Source: Unum Therapeutics Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase 1, multi-center, single-arm, open-label study evaluating the safety, tolerability, and anti-myeloma activity of ACTR087 (an autologous T cell product) in combination with SEA-BCMA (a monoclonal antibody) in subjects with relapsed or refractory Multiple Myeloma.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 15
• Est. completion date: October 1, 2019
• Est. primary completion date: October 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Signed written informed consent obtained prior to study procedures

• Histologically- or cytologically-confirmed relapsed or refractory multiple myeloma (MM) with measurable disease

• Must have received at least 3 prior lines of therapy to include treatment with a proteasome inhibitor (eg, bortezomib, carfilzomib, or ixazomib) and an immunomodulatory agent (eg, lenalidomide, pomalidomide) unless double-refractory to both; and a hematopoietic stem cell transplant (HSCT), for those subjects considered HSCT-eligible.

• Quantitative serum IgG levels for subjects with IgG MM must not exceed the institutional upper limit of normal (ULN)

• ECOG 0 or 1

• Life expectancy of at least 6 months

• Absolute neutrophil (ANC) count greater than 1000/ µL

• Platelet count greater than 50,000/µL

• Estimated GFR >30mL/min/1.73m2

Exclusion Criteria:

• Known active central nervous system (CNS) involvement by MM

• Systemic rheumatic or autoimmune diseases or acute or chronic infections

• Uncontrolled thromboembolic events or recent severe hemorrhage

• Subjects who are currently using more than 5mg/day of prednisone (or an equivalent glucocorticoid exceeding physiologic replacement levels)

• Prior treatment as follows:

• T cell-directed antibody therapy (eg. Alemtuzumab, anti-thymocyte globulin) within 6 months of enrollment

• Any prior myeloma-directed therapy including cytotoxic chemotherapy, biologic therapy, or radiotherapy within 2 weeks of enrollment

• Any mAb or other protein therapeutic containing Fc-domains within 4 weeks of enrollment

• Experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy

• Prior BCMA-directed investigational agents at any time

• Prior cell or gene therapy, excluding transfers of genetically unmodified autologous cells (eg. Hematopoietic stem cell transplantation), at any time; or prior allogeneic HSCT at any time

• Pregnant or breastfeeding

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Neoplasms, Plasma Cell
• Refractory Multiple Myeloma

Intervention

Biological:
• ACTR087
Autologous T cell product
• SEA-BCMA
B-cell maturation antigen (BCMA)-directed antibody

Locations

Country	Name	City	State
United States	Tufts Medical Center	Boston	Massachusetts
United States	Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Baylor Scott & White	Dallas	Texas
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	Mayo Clinic	Jacksonville	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Mayo Clinic	Phoenix	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Unum Therapeutics Inc.	Seattle Genetics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of ACTR087 in combination with SEA-BCMA	Composite outcome measure assessed by committee review of dose limiting toxicities (DLTs), incidence and severity of AEs and clinically significant abnormalities of laboratory values	28 days
Primary	Determination of recommended Phase 2 dosing regimen	Review of DLTs, Maximum tolerated contour (MTC), incidence and severity of AEs and clinically significant abnormalities of laboratory values	52 weeks
Secondary	Safety of SEA-BCMA as measured by incidence of Treatment Emergent Adverse Events (TEAEs)	Review of all TEAEs, including incidence and severity of AEs, DLTs and clinically significant abnormalities of laboratory values	21 days
Secondary	Anti-myeloma activity as measured by overall response rate (per IMWG response criteria)		52 weeks
Secondary	Anti-myeloma activity as measured by duration of response		52 weeks
Secondary	Anti-myeloma activity as measured by progression-free survival		52 weeks
Secondary	Anti-myeloma activity as measured by overall survival		52 weeks
Secondary	Assessment of persistence of ACTR087 as measured by flow cytometry and qPCR		52 weeks
Secondary	Assessment of ACTR087 phenotype and function as measured by flow cytometry		52 weeks
Secondary	Assessment of induction of inflammatory markers and cytokines/chemokines after ACTR087 administration	Levels of inflammatory markers, cytokines/chemokines	52 weeks
Secondary	SEA-BCMA PK	SEA-BCMA plasma concentration	52 weeks
Secondary	Assessment of anti-drug antibodies (ADA) after SEA-BCMA administration	Incidence of ADAs to SEA-BCMA	52 weeks