Evaluate Safety of Axicabtagene Ciloleucel Reinfusion (Axi-Cel-2) in Patients With Relapsed and/or Refractory Second Line High-Risk Non-Hodgkin Lymphoma After Standard of Care Axi-Cel
Study Details
Study Description
Brief Summary
This is a phase Ib study to establish safety of Axi-Cel-2 in patients with Large B Cell Lymphoma (LBCL) who are at high risk of relapse.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: Safety Run-in phase First three patients (maximum of 6) will receive 0.5 x 106/kg CART cells (25% standard dose) as reinfusion product between days 7 through 14 if CRS/ICANS has resolved to a grade 1 or less. |
Drug: Axicabtagene Ciloleucel
Subjects will receive a re-infusion of Axi-Cel (Axi-Cel-2) if signs and symptoms of cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are ≤ grade 1.
Other Names:
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Experimental: Phase 1b Up to 20 evaluable subjects will receive the target dose of AxiCel infusion to evaluate efficacy of Axi-Cel-2 in adults with high risk relapsed/refractory LBCL |
Drug: Axicabtagene Ciloleucel
Subjects will receive a re-infusion of Axi-Cel (Axi-Cel-2) if signs and symptoms of cytokine release syndrome (CRS) and Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) are ≤ grade 1.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Incidence of toxicities,dose limiting toxicity (DLT) of a second dose of AxiCel (Axi-Cel2) in adults with relapsed/refractory high-risk LBCL. [28 days]
Subjects will be assessment for dose limiting toxicity (DLT) for 28 days after the infusion of Axi-Cel-2
Secondary Outcome Measures
- Progression free survival (PFS) [12 months]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Diagnosis: Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008:
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Diffuse large B cell lymphoma (DLBCL); OR
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primary mediastinal (thymic) large B cell lymphoma; OR
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transformation of follicular lymphoma (TFL), marginal zone lymphoma to DLBCL; OR
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high grade B-cell Lymphoma NOS will also be included
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Patients must be considered high-risk lymphoma (defined as LDH greater than upper limit of normal per institutional cut-off) at or within two weeks of leukapheresis.
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Subjects must have received at least and a maximum one prior line of therapy for LBCL indication (i.e subjects receiving second line standard of care Axi-Cel will be enrolled in this study).
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At least 1 measurable lesion on PET-CT or CT scan. If the only measurable disease is lymph-node disease, at least 1 lymph node should be ≥ 1.5 cm.
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Age 18 years or older
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Eastern cooperative oncology group (ECOG) performance status of 0 or 1. ECOG 2 permitted if performance status is solely attributed to lymphoma.
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Normal Organ and Marrow Function
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ANC ≥ 1,000/uL
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Platelet count ≥ 75,000/uL
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Adequate renal, hepatic, pulmonary and cardiac function defined as:
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Creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min
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Serum ALT or AST ≤ 2.5 x ULN (except in subjects with liver involvement by lymphoma)
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Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.
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Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as determined by an Echocardiogram.
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No clinically significant pleural effusion or ascites
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Baseline oxygen saturation > 92% on room air
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Ability to understand and the willingness to sign the written IRB-approved informed consent document. Subjects unable to give informed consent will not be eligible for this study.
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Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential)
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Contraception: Subjects of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for twelve (12) months after receiving the preparative lymphodepletion regimen.
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If prior CD19 directed therapy, demonstrates CD19 positivity by biopsy (Flow cytometry or immunohistochemistry per the institutional criteria)
Exclusion Criteria:
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Prior treatment with CAR-T or adoptive cell therapy.
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Prior allogeneic transplant.
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No bridging therapy permitted except for steroids or radiotherapy (bridging therapy with steroids e.g. dexamethasone 40 mg for 5 days or radiotherapy is permitted). Measurable non-irradiated lesion post-apheresis needed for enrollment.
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Active central nervous system disease from lymphoma. MRI of the brain with no evidence of CNS lymphoma if prior history of CNS involvement.
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Prior history of allergic reactions or severe infusion reaction to Axi-Cel or any of the reagents used in the Axi-Cel infusion.
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History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma.
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Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment.
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Women who are pregnant or breastfeeding
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History of invasive malignancy unless the patient has been disease-free for five years.
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Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, and breast) is eligible.
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Hormonal therapy in subjects in remission >1 year will be allowed.
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History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication.
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In the investigator's judgment, the subject is unlikely to complete all study specific visits or procedures, including follow-up visits, or comply with the study requirements for participation.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Stanford University | Palo Alto | California | United States | 94305 |
Sponsors and Collaborators
- Stanford University
- Kite Pharma
Investigators
- Principal Investigator: Saurabh Dahiya, MD, Stanford University
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB-68723
- CCT5068