IRB Study Number 22-1171
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
Safety and tolerability of SYNCAR-001 + STK-009
Secondary Objectives
Efficacy of SYNCAR-001+STK-009
PK profile of SYNCAR-001+STK- 009
Immunogenicity of SYNCAR-001+STK-009
Inclusion Criteria
Age ≥18 years
Histologically confirmed r/r B cell malignancy to include CLL/SLL and select NHL subtypes (DLBCL, FL, MZL, and MCL) as defined by the World Health Organization Classification 4th edition (Swerdlow 2016).
Relapsed/refractory disease: subject must fulfill any one sub-criterion listed for each disease
a. CLL
−Second or greater relapse
−Any relapse after allogeneic stem cell transplantation
−Chemorefractory as defined by not achieving CR after 2 cycles of a standard induction chemotherapy or one cycle of salvage therapy
b. NHL to only include DLBCL, FL, MZL, and MCL as listed below
−Second or greater relapse
−Any relapse after allogeneic stem cell transplantation
−Chemorefractory as defined by not achieving CR after 2 cycles of a standard induction chemotherapy or one cycle of salvage therapy
- Disease-specific criteria: subject must fulfill all subcriteria listed for each disease
a. CLL/SLL
−CLL with an indication for treatment based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines and measurable disease (any of the following: bone marrow involvement by ≥30% lymphocytes, peripheral blood lymphocytosis >5×109/L, and/or measurable lymph nodes ≥1.5 cm in the greatest transverse diameter and/or hepatomegaly or splenomegaly)
−SLL (lymphadenopathy and/or splenomegaly and <5×109 CD19+ CD5+ clonal B lymphocytes/L [<5000/μL] in the peripheral blood with measurable disease defined as at least 1 lesion ≥1.5 cm in the greatest transverse diameter) that is biopsy-proven SLL
−Subjects with primary refractory or r/r disease after 2 lines of prior therapy -and- must have previously received or be intolerant to a Bruton’s tyrosine kinase (BTK) inhibitor and venetoclax, unless a BTK inhibitor or venetoclax is contraindicated according to investigator assessment.
b. LBCL
−DLBCL not otherwise specified (activated B cell and germinal center B cell); high- grade B cell lymphoma with or without c-myc and bcl-2 and/or bcl-6 rearrangement; DLBCL arising from FL or other indolent lymphoma; T cell/histiocyte-rich large B cell lymphoma; DLBCL associated with chronic inflammation; primary cutaneous DLBCL, leg type; Epstein-Barr virus +DLBCL; Richter’s transformation; FL Grade 3b; and primary mediastinal B cell lymphoma
−Subjects must have been treated with an anthracycline and rituximab (or another CD20-targeted agent) and have r/r disease after at least 2 lines of systemic therapy.
c. Indolent B cell NHL
−FL Grade 1, 2, or 3a and MZL, nodal or extranodal
−Subjects with primary refractory or r/r disease after 2 or more prior lines of therapy and at least 1 of the prior lines of therapy must include an anti-CD20 antibody therapy.
d. MCL
−Histology confirmed with cyclin D1 expression or evidence of t (11;14) by cytogenetics, fluorescence in situ hybridization, or polymerase chain reaction (PCR)
−Primary refractory or r/r disease after at least 2 prior lines of systemic therapy, including an alkylating agent, BTK inhibitor and rituximab (or another CD20- targeted agent).
Documentation of CD19 expression by immunohistochemistry or flow cytometry on any prior or current tumor specimen (or peripheral blood for circulating disease) or high likelihood of CD19 expression based on disease histology.
Subject must have been considered for a commercial CD19 CART by the treating physician (when applicable).
Subject must have no signs or 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.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of <2.
Adequate organ function as defined below:
a. Serum creatinine ≤1.5 × age-adjusted upper limit of normal (ULN) or creatinine clearance (as estimated by the Cockcroft-Gault formula) >30 mL/min
b. Cardiac ejection fraction ≥40% as assessed by echocardiogram (ECHO) or multigated acquisition scan (MUGA) and no evidence of clinically significant pericardial effusion.
c. No clinically significant pleural effusion
d. Oxygen saturation ≥92% in room air.
e. Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤3 times the ULN and total bilirubin ≤2.0
f. Serum ALT/AST ≤5 times the ULN and total bilirubin ≤3.0 for subjects with Gilbert’s syndrome or tumor infiltration of the liver
- Adequate hematologic function as defined below (unless cytopenias judged by the investigator are due to underlying disease):
a. Platelet count ≥ 50000/μL
b. Absolute neutrophil count of ≥ 1000/μL
c. Absolute lymphocyte count > 100/μL
Evidence of measurable disease per Lugano Classification for NHL (Appendix 1) or per iwCLL for CLL/SLL (Appendix 2)
Absence of response (CR or partial response [PR]) to the last line of therapy or progression of disease after response
Subjects of childbearing potential (Appendix 4) must have a negative serum or urine pregnancy test at baseline (subjects who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential).
Willing to practice highly effective birth control (Appendix 4) and refrain from donating sperm or oocytes from the time of enrollment in this study through 3 months after receiving the study treatment
Capable of providing informed consent
Exclusion Criteria
Prior CD19-directed therapy including CD19 CARTs
Current need for urgent therapy due to mass effect or rapidly progressive disease
Presence of a fever with suspicion of an infection that is uncontrollable with a 72-hour course of antibiotics. Prophylactic antimicrobials are allowed.
Active hepatitis B or hepatitis C infection. History of hepatitis B or hepatitis C is permitted with a negative PCR assay for viral load.
History of or active human immunodeficiency virus (HIV) infection
History of severe immediate hypersensitivity reaction to agents used in this study (e.g., aminoglycosides, dimethyl sulfoxide [DMSO], and polyethylene glycol [PEG])
History or presence of significant CNS disorder, such as seizure disorder, cerebrovascular disease, dementia, or autoimmune disease with CNS involvement
Cardiac involvement with lymphoma
History of myocardial infarction, cardiac angioplasty, unstable angina, cerebral vascular accident/stroke, congestive heart failure (New York Heart Association Classification Class II), serious cardiac arrhythmia requiring medication, or other clinically significant cardiac diseases within 6 months of enrollment
Known primary immunodeficiency
History of autoimmune disease requiring systemic immunosuppressive or disease- modifying therapy within 6 months of enrollment
History of deep vein thrombosis or pulmonary embolism requiring anticoagulant therapy within 6 months of enrollment
Presence of any medical condition that may interfere with evaluation of efficacy or safety according to investigator assessment
History of other malignancy within 2 years of enrollment, except curatively treated malignancies or malignancies with low risk of recurrence.
Autologous hematopoietic stem cell transplant within 6 weeks of enrollment
Prior allogeneic hematopoietic stem cell transplant within 6 months of enrollment
Presence of GVHD
Prior solid organ transplant requiring systemic immunosuppressive therapy
Use of any anticancer therapy (including experimental therapies) within 2 weeks or 5 half-lives (whichever is shorter) prior to enrollment. Systemic steroids (greater than physiologic replacement therapy) are allowed up to 7 days prior to enrollment. Bridging therapy following enrollment is allowed as described in Section 7.3.
Prior treatment with IL-2 within 6 weeks of enrollment
Investigator assessment that the subject may not be able to complete all protocol-required visits or procedures or comply with the study protocol
Subjects who are currently pregnant or breast feeding
Treatment with a live, attenuated vaccine within 4 weeks prior to the planned 1st dose of STK-009 and during the course of the study is prohibited
