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

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Trial ID: NCT05794958

Purpose

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.

Official Title

A Phase Ib, Open Label Study to 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

Stanford Investigator(s)

Saurabh Dahiya, MD, FACP
Saurabh Dahiya, MD, FACP

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Matthew Frank

Assistant Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Lori Muffly
Lori Muffly

Associate Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

David Miklos
David Miklos

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Robert Negrin
Robert Negrin

Professor of Medicine (Blood and Marrow Transplantation and Cellular Therapy)

Eligibility


Inclusion Criteria:

   1. Diagnosis: Histologically confirmed aggressive B cell NHL including the following
   types defined by WHO 2008:

      - Diffuse large B cell lymphoma (DLBCL); OR

      - primary mediastinal (thymic) large B cell lymphoma; OR

      - transformation of follicular lymphoma (TFL), marginal zone lymphoma to DLBCL; OR

      - high grade B-cell Lymphoma NOS will also be included

   2. 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.

   3. 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).

   4. 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.

   5. Age 18 years or older

   6. Eastern cooperative oncology group (ECOG) performance status of 0 or 1. ECOG 2
   permitted if performance status is solely attributed to lymphoma.

   7. Normal Organ and Marrow Function

      - ANC ≥ 1,000/uL

      - Platelet count ≥ 75,000/uL

      - Adequate renal, hepatic, pulmonary and cardiac function defined as:

         - Creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min

         - Serum ALT or AST ≤ 2.5 x ULN (except in subjects with liver involvement by
         lymphoma)

         - Total bilirubin ≤ 1.5 mg/dl, except in subjects with Gilbert's syndrome.

         - Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as
         determined by an Echocardiogram.

      - No clinically significant pleural effusion or ascites

      - Baseline oxygen saturation > 92% on room air

   8. 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.

   9. 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)

10. 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.

11. If prior CD19 directed therapy, demonstrates CD19 positivity by biopsy (Flow cytometry
   or immunohistochemistry per the institutional criteria)

Exclusion Criteria:

   1. Prior treatment with CAR-T or adoptive cell therapy.

   2. Prior allogeneic transplant.

   3. 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.

   4. Active central nervous system disease from lymphoma. MRI of the brain with no evidence
   of CNS lymphoma if prior history of CNS involvement.

   5. Prior history of allergic reactions or severe infusion reaction to Axi-Cel or any of
   the reagents used in the Axi-Cel infusion.

   6. History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic
   lymphoma, or lymphoplasmacytic lymphoma.

   7. Any medical condition that in the judgement of the investigator is likely to interfere
   with assessment of safety or efficacy of study treatment.

   8. Women who are pregnant or breastfeeding

   9. History of invasive malignancy unless the patient has been disease-free for five
   years.

      - Exception: Nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder,
      and breast) is eligible.

      - Hormonal therapy in subjects in remission >1 year will be allowed.

10. History of stroke or transient ischemic attack within 12 months before enrollment, or
   seizure disorders requiring active anticonvulsive medication.

11. 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.

Intervention(s):

drug: Axicabtagene Ciloleucel

Recruiting

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Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Kelly Chyan, MPH
650-725-8130

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