Study Evaluating SC291 in Subjects With r/r B-cell Malignancies (ARDENT)

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

A Phase 1 Study Evaluating SC291, a Hypoimmune, Allogeneic CD19-directed CAR T Cell Therapy, in Relapsed and/or Refractory B-cell Malignancies (ARDENT)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05878184
• Other study ID #: SC291-101
• Status: Recruiting
• Phase: Phase 1
• Start date: May 2, 2023
• Est. completion date: December 2027

Study information

• Verified date: April 2024
• Source: Sana Biotechnology
• Contact: Ndidi Onwudiwe
• Phone: 206 791 3731
• Email: ardent[@]sana.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SC291-101 is a Phase 1 study to evaluate SC291 safety and tolerability, anti-tumor activity, cellular kinetics, immunogenicity, and exploratory biomarkers.

Description:

This is an open-label, single arm, Phase 1, first-in-human (FIH) study to evaluate the safety and tolerability of SC291 administered intravenously (IV) following a standard lymphodepleting chemotherapy regimen of cyclophosphamide and fludarabine in subjects with NHL or CLL who have received two or more prior systemic treatments per standard of care (or after autologous stem cell transplant [ASCT] for NHL). This study will be conducted in 2 parts. Phase 1a: dose finding using a 3+3 design in subjects with NHL or CLL. Phase 1b: dose expansion to further evaluate safety and efficacy at the RP2D in subjects with LBCL and CLL.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 57
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Male or female subjects aged 18-80 years at the time of signing informed consent.
• Diagnosis of NHL (WHO 2016 criteria) or CLL (iwCLL criteria), including:
• Large B-cell lymphoma, including diffuse large B-cell lymphoma (DLBCL) not otherwise -
• specified (including DLBCL arising from indolent lymphoma), primary mediastinal large -- - B-cell lymphoma, high grade B-cell lymphoma, follicular lymphoma grade 3B
• Follicular lymphoma (dose escalation only except for follicular lymphoma grade 3B)
• Marginal zone lymphoma (dose escalation only)
• Mantle cell lymphoma (dose escalation only)
• CLL or SLL
• Relapsed/refractory disease after at least 2 prior systemic regimens per standard of care or after autologous stem cell transplant
• ECOG performance status of 0 or 1.
• At least one measurable lesion per Lugano Classification (NHL); CLL subjects must meet iwCLL treatment criteria
• Life expectancy =12 weeks

Exclusion Criteria:

• Prior anti-CD19 therapy including CD19-directed CAR T treatment or other CD19-directed antibody or cell therapy (e.g., NK cell). (Part 2 dose expansion only - prior approved CD19-directed CAR T therapy required)
• History of primary central nervous system (CNS) lymphoma or presence of CNS metastases
• Systemic anticancer therapy (including platinum-based chemotherapies and I/O therapies) or radiotherapy within 14 days of SC291 (28 days for biologics)
• Autologous HSCT within 6 weeks of treatment with SC291 (or allogeneic HSCT at any time).
• Active autoimmune disease or any other diseases requiring immunosuppressive therapy or corticosteroid therapy (defined as >20 mg/day prednisone or equivalent).
• History or presence of cardiac or CNS disorders as defined in the protocol

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• SC291
SC291 is an allogeneic CAR-T cell therapy

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Centre	Melbourne	Victoria
United States	Northside Hospital	Atlanta	Georgia
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	City of Hope	Duarte	California
United States	University of Kansas Medical Center	Fairway	Kansas
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Stanford Cancer Institute	Palo Alto	California

Sponsors (1)

Lead Sponsor	Collaborator
Sana Biotechnology

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate safety and tolerability of SC291	Safety and Tolerability: Proportion of subjects experiencing adverse events and dose-limiting toxicities	24 months
Secondary	Evaluate preliminary anti-tumor activity of SC291	Preliminary anti-tumor activity: Proportion of subjects with an objective response (including partial response or complete response)	24 months
Secondary	Evaluate cellular kinetics and persistence of SC291	Cellular kinetics-related parameters evaluated by CAR T cell copy number	24 months
Secondary	Evaluate cellular kinetics and persistence of SC291	Cellular kinetics related peak (Cmax) in peripheral blood	24 months
Secondary	Evaluate cellular kinetics and persistence of SC291	Area under the concentration time curve (AUC) in peripheral blood	24 months
Secondary	Evaluate host immunogenicity to SC291	Incidence of anti-CD19-directed CAR antibodies	24 months