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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

Primary Purpose

Non-Hodgkin Lymphoma, Large B-cell Lymphoma

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Axicabtagene Ciloleucel
Sponsored by
Stanford University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 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. 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). 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. Age 18 years or older Eastern cooperative oncology group (ECOG) performance status of 0 or 1. ECOG 2 permitted if performance status is solely attributed to lymphoma. 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 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. 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) 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. If prior CD19 directed therapy, demonstrates CD19 positivity by biopsy (Flow cytometry or immunohistochemistry per the institutional criteria) Exclusion Criteria: Prior treatment with CAR-T or adoptive cell therapy. Prior allogeneic transplant. 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. Active central nervous system disease from lymphoma. MRI of the brain with no evidence of CNS lymphoma if prior history of CNS involvement. Prior history of allergic reactions or severe infusion reaction to Axi-Cel or any of the reagents used in the Axi-Cel infusion. History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma. Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment. Women who are pregnant or breastfeeding 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. History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication. 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.

Sites / Locations

  • Stanford UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Safety Run-in phase

Phase 1b

Arm Description

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.

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

Outcomes

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.
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)

Full Information

First Posted
March 20, 2023
Last Updated
July 13, 2023
Sponsor
Stanford University
Collaborators
Kite Pharma
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1. Study Identification

Unique Protocol Identification Number
NCT05794958
Brief Title
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
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 23, 2023 (Actual)
Primary Completion Date
April 1, 2038 (Anticipated)
Study Completion Date
April 1, 2038 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
Kite Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin Lymphoma, Large B-cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Safety Run-in phase
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Phase 1b
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Axicabtagene Ciloleucel
Other Intervention Name(s)
(Axi-cel-2)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence of toxicities,dose limiting toxicity (DLT) of a second dose of AxiCel (Axi-Cel2) in adults with relapsed/refractory high-risk LBCL.
Description
Subjects will be assessment for dose limiting toxicity (DLT) for 28 days after the infusion of Axi-Cel-2
Time Frame
28 days
Secondary Outcome Measure Information:
Title
Progression free survival (PFS)
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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. 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). 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. Age 18 years or older Eastern cooperative oncology group (ECOG) performance status of 0 or 1. ECOG 2 permitted if performance status is solely attributed to lymphoma. 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 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. 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) 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. If prior CD19 directed therapy, demonstrates CD19 positivity by biopsy (Flow cytometry or immunohistochemistry per the institutional criteria) Exclusion Criteria: Prior treatment with CAR-T or adoptive cell therapy. Prior allogeneic transplant. 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. Active central nervous system disease from lymphoma. MRI of the brain with no evidence of CNS lymphoma if prior history of CNS involvement. Prior history of allergic reactions or severe infusion reaction to Axi-Cel or any of the reagents used in the Axi-Cel infusion. History of Richter's transformation of chronic leukemic lymphoma, small lymphocytic lymphoma, or lymphoplasmacytic lymphoma. Any medical condition that in the judgement of the investigator is likely to interfere with assessment of safety or efficacy of study treatment. Women who are pregnant or breastfeeding 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. History of stroke or transient ischemic attack within 12 months before enrollment, or seizure disorders requiring active anticonvulsive medication. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kelly Chyan, MPH
Phone
(650) 725-8130
Email
kchyan@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saurabh Dahiya, MD
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Palo Alto
State/Province
California
ZIP/Postal Code
94305
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kelly Chyan, MPH
Phone
650-725-8130
Email
kchyan@stanford.edu
First Name & Middle Initial & Last Name & Degree
Sally Arai, MD
First Name & Middle Initial & Last Name & Degree
Laura Johnston, MD
First Name & Middle Initial & Last Name & Degree
Robert Lowsky, MD
First Name & Middle Initial & Last Name & Degree
Everett Meyer, MD, PhD
First Name & Middle Initial & Last Name & Degree
Robert Negrin, MD
First Name & Middle Initial & Last Name & Degree
Andrew Rezvani, MD
First Name & Middle Initial & Last Name & Degree
Judith Shizuru, MD, PhD
First Name & Middle Initial & Last Name & Degree
Wen-Kai Weng, MD, PhD
First Name & Middle Initial & Last Name & Degree
Praveen Shiraz, MD
First Name & Middle Initial & Last Name & Degree
Matthew Frank, MD, PhD
First Name & Middle Initial & Last Name & Degree
Surbhi Sidana, MD
First Name & Middle Initial & Last Name & Degree
Lori Muffly, MD, MS
First Name & Middle Initial & Last Name & Degree
Melody Smith, MD
First Name & Middle Initial & Last Name & Degree
David B. Miklos, MD, PhD

12. IPD Sharing Statement

Learn more about this trial

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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