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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-Hodgkin Lymphoma; Large B-cell Lymphoma
• Intervention / Treatment: Drug: Axicabtagene Ciloleucel

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Kelly Chyan, MPH; Phone Number: (650) 725-8130; Email: kchyan@stanford.edu

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford University
      • Sub-Investigator: Wen-Kai Weng, MD, PhD
      • Sub-Investigator: Melody Smith, MD
      • Contact: Kelly Chyan, MPH; Phone Number: 650-725-8130; Email: kchyan@stanford.edu
      • Sub-Investigator: Lori Muffly, MD, MS
      • Sub-Investigator: Sally Arai, MD
      • Sub-Investigator: Laura Johnston, MD
      • Sub-Investigator: Robert Lowsky, MD
      • Sub-Investigator: Everett Meyer, MD, PhD
      • Sub-Investigator: Robert Negrin, MD
      • Sub-Investigator: Andrew Rezvani, MD
      • Sub-Investigator: Judith Shizuru, MD, PhD
      • Sub-Investigator: Praveen Shiraz, MD
      • Sub-Investigator: Matthew Frank, MD, PhD
      • Sub-Investigator: Surbhi Sidana, MD
      • Sub-Investigator: David B. Miklos, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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: (Axi-cel-2)
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: (Axi-cel-2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of toxicities,dose limiting toxicity (DLT) of a second dose of AxiCel (Axi-Cel2) in adults with relapsed/refractory high-risk LBCL.	Subjects will be assessment for dose limiting toxicity (DLT) for 28 days after the infusion of Axi-Cel-2	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression free survival (PFS)	12 months

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Kite Pharma
• Investigators: Principal Investigator: Saurabh Dahiya, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Estimated): April 1, 2038
• Study Completion (Estimated): April 1, 2038

Study Registration Dates

• First Submitted: March 20, 2023
• First Submitted That Met QC Criteria: March 20, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): July 17, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Antineoplastic Agents, Immunological; Axicabtagene ciloleucel
• Other Study ID Numbers: IRB-68723; CCT5068 (Other Identifier: OnCore)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No