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Tests treatment safety and results for Non-Hodgkin Lymphoma
Official title Preliminary Safety and Tolerability of CD19x22 CAR T Cells in Adolescent and Adult R/R B-NHL Patients
ClinicalTrials.gov ID: NCT05098613
What this study is testing
What is CD19x22 CAR T Cells?
CD19x22 CAR T Cells is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for non-hodgkin lymphoma.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This open-label, single arm phase 1 trial aims to determine the safety and tolerability of anti-CD19 and anti-CD22 chimeric antigen receptor-expressing (CAR) T cells (CD19x22 CAR T) in adolescents and adults with relapsed/refractory (R/R) B-cell Non-Hodgkin Lymphoma (B-NHL). This trial will determine the maximum tolerated dose of CD19x22 CAR T cells using a standard 3+3 trial design.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 16 and older
You may be able to join if
- Age: ≥ 16 years of age with no upper age limit. (NOTE: the first three people on this trial must be ≥ 18 years of age.) COHORT 1: Non-CNS B-NHL
- Histologically confirmed aggressive B-cell NHL including the following types defined by World Health Organization (WHO) 2008:
- Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic...
- Primary mediastinal (thymic) large B cell lymphoma; OR
- Transformation to DLBCL; OR
You likely can't join if
- Age \< 16 years of age.
- Patients who are intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.
- Patients with active, poorly controlled hydrocephalus defined as increase/worsening in symptoms (headaches, nausea/vomiting, lethargy, or...
- Patients with brainstem lesions. Only applicable to Cohort 3.
- History of other malignancies, unless they have been disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in...
- Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; uncomplicated infections are permitted if...
See the full eligibility criteria
Who can join
- Age: ≥ 16 years of age with no upper age limit. (NOTE: the first three people on this trial must be ≥ 18 years of age.) COHORT 1: Non-CNS B-NHL
- Histologically confirmed aggressive B-cell NHL including the following types defined by World Health Organization (WHO) 2008:
- Diffuse Large B-Cell Lymphoma (DLBCL) not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr Virus (EBV)+ DLBCL of the elderly; OR
- Primary mediastinal (thymic) large B cell lymphoma; OR
- Transformation to DLBCL; OR
- High grade B-cell Lymphoma (HGBL).
- people must not have any signs or symptoms of CNS disease or detectable evidence of CNS disease on magnetic resonance imaging (MRI) at screening; people who have been previously treated for CNS disease, but have no...
- people must have disease progression confirmed by either flow cytometry or immunohistochemistry (IHC), disease stabilization, or disease recurrence after at least two lines of therapy.
- The two lines of prior therapy must include an anthracycline and anti-CD20 monoclonal antibody treatment.
- Relapse or refractory after single antigen targeting CAR T cell therapy
- Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable...
- Mantle Cell Lymphoma (MCL).
- Results of all tests conducted on the tissue at initial diagnosis and/or relapse, including, but not limited to, the MCL subtype (classic and blastoid), Ki-67 proliferation index, and TP53 mutation status should be...
- people must have relapsed and/or refractory MCL confirmed by either flow cytometry or immunohistochemistry (ICH), disease stabilization, or disease recurrence after at least two lines of therapy including any...
- An anti-CD20-directed therapy
- A BTK inhibitor
- Anthracycline or Bendamustine
- Relapse or refractory after single antigen targeting CAR T cell therapy.
- Must have evaluable or measurable disease according to the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma; lesions that have been previously irradiated will be considered measurable...
- people with relapsed and/or refractory primary CNS lymphoma (PCNSL) OR secondary CNS lymphoma (SCNSL), as defined by the following: a. Absence of measurable disease outside the CNS, as determined by radiographic imaging...
- people must have disease progression confirmed by either flow cytometry or immunohistochemistry (IHC), disease stabilization, or disease recurrence after at least one line of therapy. ALL COHORTS:
- people who have undergone autologous stem cell transplantation (SCT) with disease progression or relapse are eligible.
- people who have undergone allogeneic SCT will be eligible if, in addition to meeting other eligibility criteria, are:
- At least 100 days post-transplant,
- Do not have active graft versus host disease (GVHD)
- Any standard of care systemic therapy prior to leukapheresis must follow the washout period.
- Any steroid use (dexamethasone or prednisone) prior to apheresis must follow the washout period. Physiological replacement doses are allowable with no washout period. Topical or inhaled steroids for localized GVHD is...
- Peripheral blood CD3 count must be \>0.15 x 10 (to the 6th) cells/mL within 14 days prior to proceeding with apheresis.
- Toxicities from prior therapy must be stable and recovered to ≤ grade 1 (exceptions include non-clinically significant toxicities such as alopecia and the organ function definitions provided in 12).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, or Karnofsky ≥ 80%.
- Adequate organ function as defined by:
- Absolute neutrophil count (ANC) ≥ 500/μL
- Platelet count ≥ 50,000/ μL.
- Renal: Creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL/min.
- Hepatic: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN).
- Total bilirubin ≤ 2 mg/dl, except in people with Gilbert's syndrome where a bilirubin \<4.0 will be acceptable.
- Cardiac: Ejection fraction ≥ 40%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings within 6 weeks...
- Pulmonary: No clinically significant pleural effusion and; i. Baseline oxygen saturation must be \> 92% on room air
- Females of childbearing potential must have a negative serum pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 6 months are not considered to be of...
- people of childbearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for 12 months after receiving the CD19x22 infusion; females of childbearing...
What rules you out
- Age \< 16 years of age.
- Patients who are intolerant of contrast-enhanced MRI due to allergic reactions to contrast agents. Only applicable to Cohort 3.
- Patients with active, poorly controlled hydrocephalus defined as increase/worsening in symptoms (headaches, nausea/vomiting, lethargy, or neurological function with increased hydrocephalus noted on radiologic evaluation...
- Patients with brainstem lesions. Only applicable to Cohort 3.
- History of other malignancies, unless they have been disease free for at least 3 years. Exceptions include non-melanoma skin cancer or carcinoma in situ and localized prostate cancer not on active treatment.
- Uncontrolled fungal, bacterial, viral, or other infection requiring antimicrobials for management; uncomplicated infections are permitted if responding to active treatment.
- Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (hepatitis B surface antigen [HBsAg] positive) or hepatitis C.
- History of known myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment or have cardiac atrial or cardiac ventricular...
- Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.
- Any medical condition that in the judgement of the sponsor is likely to interfere with assessment of safety or how well it works of study treatment.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Pregnancy (serum pregnancy test must be obtained at time of enrollment for females of childbearing potential and to be repeated 72 hours prior to lymphodepleting chemotherapy regimen); females who have undergone...
- Lactating.
- In the investigator's judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation.
- Unwilling to participate in long-term follow-up protocol that is required if CAR T cell therapy is administered at CU Anschutz. APHERESIS ELIGIBILITY In order to proceed with apheresis, enrolled participants cannot have...
- Positive blood culture within 48 hours of the start of the apheresis procedure, OR
- Fever \>38.2°C AND clinical signs of infection within 48 hours of start of apheresis procedure Additionally, participants should have the following labs within 14 days of apheresis:
- CBC with manual differential
- Lymphocyte enumeration (TBNK) panel to measure CD3 count
- CD3 count must be \>0.15 x 106 cells/mL LYMPHODEPLETING CHEMOTHERAPY ELIGIILITY: In order to proceed with lymphodepleting chemotherapy, enrolled participants must meet all eligibility criteria below within 72 hours...
- If the participant received bridging therapy after apheresis, confirmation of disease reevaluation is required. It must be within 6 weeks of initiation of LD chemotherapy.
- Confirmation that the participant has met the washout period for bridging therapy.
- Negative serum pregnancy test (for women of childbearing potential)
- Adequate organ function as defined by:
- Absolute neutrophil count (ANC) ≥ 500/μL.
- Platelet count ≥ 50,000/ μL.
- Renal: Creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by Cockcroft Gault equation) ≥ 60 mL/min.
- Hepatic: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3 upper limit of normal (ULN).
- Total bilirubin ≤ 2 mg/dl, except in people with Gilbert's syndrome where a bilirubin \<3.0 will be acceptable.
- Pulmonary: No clinically significant pleural effusion and; Baseline oxygen saturation must be \> 92% on room air.
- Cardiac: Ejection fraction ≥ 45%, no evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO) (only if subject received bridging anthracycline or developed a significant...
- Cohort 3 patients ONLY:
- Patients must not have steroid-dependent CNS lymphoma, defined as requiring more than 1 mg/kg/day or prednisone or equivalent within 14 days prior to the start of LD chemotherapy.
- Patients may not have poorly controlled hydrocephalus prior to the initiation of LD chemotherapy. CD19x22 CAR T CELL INFUSION ELIGIBILITY In order to proceed with CD19x22 CAR T Cell Infusion, enrolled participants must...
- CD19x22 CAR T cells must have met manufacturing release criteria (unless prospectively approved by IND Sponsor, Gates Institute Medical Lead, and FDA).
- Confirmation that the site has Anakinra and Ruxolitinib in stock and available (should IEC-HS treatment be required).
- ECOG ≤2 or Karnofsky≥ 50%.
- Clinically stable without evidence of vital sign instability, including the lack of supportive vasoactive drugs or intensive care unit support.
- Oxygen saturation \> 92% on room air; cannot be on supplemental oxygen.
- No evidence of uncontrolled, significant tumor lysis syndrome prior to cell infusion per investigator assessment.
- No evidence of rapidly progressive NHL per investigator determination.
- Participants' temperature is \<38.0 °C within 48 hours prior to cell infusion. (If the source of fever cannot be identified [after thorough infectious disease work-up], and the suspected cause is underlying malignancy...
- Liver transaminase (ALT and AST) \< 5 x institutional ULN (\< grade 3) based on age- and laboratory- specific normal ranges.
- Adequate renal function as defined by creatinine ≤ 2 mg/dL OR creatinine clearance (as estimated by the Cockcroft- Gault equation) ≥ 60 mL/min. If these criteria are not met, measures can be taken to resolve the...
The study team makes the final eligibility decision.
Where it's taking place
- Aurora, Colorado, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 16 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Aurora, Colorado, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.