Clinical trial NCT05665062: Autologous CD19 CAR-T Cell Therapy (SYNCAR-001) + Orthogonal IL-2 (STK-009) in Subjects With CD19+ Hematologic Malignancies
Official title: A Phase 1 Study to Evaluate the Safety and Tolerability of a Combination Autologous CD19 CAR T Cell Therapy (SYNCAR-001 + STK-009) in Subjects With Relapsed or Refractory CD19+ Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: CLL/SLL
NHL
Mantle Cell Lymphoma
Follicular Lymphoma
Large B-cell Lymphoma
Indolent B-Cell Non-Hodgkin Lymphoma
Diffuse Large B Cell Lymphoma
Keywords: CART
CD19-CART
Chimeric antigen receptor
IL-2
Lead sponsor: Synthekine
Sponsor class: INDUSTRY
First posted: 2022-12-27
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a first-in-human phase 1 study of SYNCAR-001 + STK-009 in patients with CD19+ hematologic malignancies.

Detailed description: SYNCAR-001 + STK-009 is a 2-component human orthogonal (ho) IL-2 receptor-ligand cell therapy consisting of (1) SYNCAR-001, a CD19-directed chimeric antigen receptor T cell (CAR-T) co-expressing an engineered IL-2 beta receptor (hoRb); and (2) STK-009, an engineered pegylated IL-2 cytokine (hoIL-2) selective for hoRb. The study will follow a 3+3 design during dose escalation. Cohort A will enroll subjects to SYNCAR-001 + STK-009 with lymphodepletion. At Dose Level 3, a separate dose escalation cohort will be introduced to enroll subjects to SYNCAR-001 + STK-009 without lymphodepletion (Cohort B). Subsequent dose expansions will enroll subjects at the RP2D for each cohort.

Eligibility criteria: Selected Inclusion Criteria:

1. Histologically confirmed relapsed/refractory hematologic malignancies, including Chronic Lymphocytic Lymphoma (CLL/SLL) and selected Non-Hodgkin's Lymphoma (NHL)
2. Prior or current documentation of CD19 expression or high likelihood of CD19 expression based on disease histology
3. No signs of symptoms of central nervous system (CNS) disease or detectable evidence of CNS or meningeal disease on magnetic resonance imaging (MRI) at the time of screening

Selected Exclusion Criteria:

1. Prior CD19 directed therapy including CD19 CARTs
2. Prior allogeneic hematopoietic stem cell transplant within 6 months of enrollment
3. Prior autologous hematopoietic stem cell transplant within 6 weeks of enrollment.
4. Presence of GVHD

Primary outcomes:
measure: Dose Limiting Toxicities (DLTs)
timeFrame: Up to 28 days post infusion (SYNCAR-001+STK-009)
measure: Adverse events
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
measure: Duration of Response (DOR)
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
measure: Progression Free Survival (PFS)
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
measure: Area under the curve (AUC)
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
measure: Maximum Concentration (Cmax)
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
measure: Time of maximum concentration
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
measure: Immunogenicity
timeFrame: Up to 24 months post infusion (SYNCAR-001+STK-009)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Buffalo
country: United States
facility: Roswell Park
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
Study officials:
References: