Clinical trial NCT05878184: Study Evaluating SC291 in Subjects With r/r B-cell Malignancies (ARDENT)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non Hodgkin Lymphoma
Chronic Lymphocytic Leukemia
Keywords: Large B cell lymphoma
CAR T Cell Therapy
Mantle cell lymphoma
Indolent follicular lymphoma
Marginal zone lymphoma
High-grade B cell lymphoma
Primary mediastinal B cell lymphoma
Diffuse large B cell lymphoma
Non-Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Allogeneic
Hypoimmune
CD19
Lead sponsor: Sana Biotechnology
Sponsor class: INDUSTRY
First posted: 2023-05-26
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Evaluate safety and tolerability of SC291
timeFrame: 24 months
Secondary outcomes:
measure: Evaluate preliminary anti-tumor activity of SC291
timeFrame: 24 months
measure: Evaluate cellular kinetics and persistence of SC291
timeFrame: 24 months
measure: Evaluate cellular kinetics and persistence of SC291
timeFrame: 24 months
measure: Evaluate cellular kinetics and persistence of SC291
timeFrame: 24 months
measure: Evaluate host immunogenicity to SC291
timeFrame: 24 months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Palo Alto
country: United States
facility: Stanford Cancer Institute
state: California
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Fairway
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
state: Western Australia
Study officials:
affiliation: Sana Biotechnology, Inc.
name: Cori Abikoff, MD
role: STUDY_DIRECTOR
References: