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CD30 CAR for CD30+ NSGCT

Primary Purpose

Germ Cell Tumor, Nonseminomatous Germ Cell Tumor

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ATLCAR.CD30 Cells
Cyclophosphamid
Fludarabine
Sponsored by
UNC Lineberger Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Germ Cell Tumor focused on measuring cellular therapy, modified T cells, ATLCAR.CD30, biobank, repository, specimen

Eligibility Criteria

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

Inclusion Criteria: Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information explained to, understood by, and signed by the subject or legally authorized representative. Age ≥ 18 years at the time of consent. Histologically confirmed diagnosis of Nonseminomatous Germ Cell Tumors (NSGCT) of any primary site. Subjects must have received at least one prior line of therapy for their NSGCT and meet one of the following criteria. There is no maximum number of prior lines of treatment allowed. Evidence of progressive or recurrent NSGCT after prior high-dose chemotherapy (HDCT) treatment, defined as meeting at least one of the following criteria: i. Tumor biopsy of new or growing or unresectable lesions demonstrating viable NSGCT. In the event of an incomplete gross resection where viable NSGCT is found, subjects will be considered eligible for the study. ii. Consecutive elevated serum tumor markers (β-HCG or AFP) are increasing. An increase of elevated lactate dehydrogenase (LDH) alone does not constitute progressive disease. iii. Development of new or enlarging lesions in the setting of persistently elevated β-HCG or AFP, even if the β-HCG and AFP are not continuing to rise. Exclusion Criteria: Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated in the study). Active infection with HIV, human T-cell leukemia virus, hepatitis B virus, and hepatitis C virus (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies or PCR negative for HTLV1 and 2, negative for Hepatitis B surface antigen, and negative for HCV antibody or HCV viral load.

Sites / Locations

  • Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel HillRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ATLCAR.CD30

Arm Description

Single Group Assignment: Subjects with Nonseminomatous Germ Cell Tumors who meet eligibility criteria for cellular therapy.

Outcomes

Primary Outcome Measures

The Overall response rate (ORR)- Response Evaluation Criteria In Solid Tumors Criteria (RECIST)
ORR - RECIST will be assessed per RECIST v1.1. criteria which define Complete Response (CR) as the disappearance of all target lesions, pathological lymph node (LN) <10mm, and normalization of serum tumor markers; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions serum tumor markers (AFP and β-hCG) should be stable or decreasing. ; and Overall Response Rate (ORR) = CR + PR/total number of subjects.

Secondary Outcome Measures

The Overall response rate (ORR)- Per immune-related Response Evaluation Criteria (irRECIST)
ORR -irRECIST will be assessed per irRECIST criteria which defines complete response (irCR), the disappearance of all lesions, no new lesions, lymph nodes < 10 mm in short axis; partial response (irPR), ≥30% decrease in the sum of target lesions and non-target lesions are irNN; Stable response (irSD), not meeting criteria for irCR, irPR, or irPD; Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir; for no new non-target or (irNN) and where irPR or irPD are confirmed by a repeat, consecutive assessment.
The best overall response rate (BORR)
BORR will be defined as the best response recorded after the administration of the cell therapy to the date of disease progression per modified RECIST 1.1, or death as a result of any cause.
Progression free survival (PFS)
PFS will be defined per modified RECIST 1.1 criteria. PFS is defined from the day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at the time of cell infusion) or progression (in patients without a complete response at the time of cell infusion), or death as a result of any cause per modified RECIST 1.1 criteria classification.
Median Progression free survival (PFS)
Median PFS is defined from the day of initial lymphodepletion administration of the first ATLCAR.CD30 product infusion to the date of disease progression per modified RECIST 1.1 criteria or death as a result of any cause.
Duration of response (DOR)
DOR will be defined as the time from documentation of PR or better to PD as defined by modified RECIST 1.1 criteria. Progressive Disease (PD) - At least a 20% increase in the sum of the longest diameter (LD) of the target lesions, a relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm or the appearance of one or more new lesion or unequivocal progression of non-target or non-measurable lesions (e.g. worsening bone pain requiring radiation or significant increase in pain medications) or increase ≥ 50% in AFP or β-hCG.
The percentage of improvement
The percentage of subjects who have an improvement in their response per modified RECIST 1.1.
Adverse Events CTCAE
Adverse Events CTCAE will be classified and graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Cytokine Release Syndrome (CRS)
Cytokine Release Syndrome (CRS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild (Symptomatic Management): Fever ≥38oC, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38oC, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe (Aggressive Intervention): Fever ≥38oC , Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g., continuous positive airway pressure (CPAP), BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.
Immune effector cell-associated neurotoxicity syndrome (ICANS)
Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
Overall survival
Overall survival will be defined from the day of initial lymphodepletion for the first administration ATLCAR.CD30 cells to date of death.
Persistence and expansion of ATLCAR.CD30
Persistence and expansion of ATLCAR.CD30 in peripheral blood will be determined by quantitative polymerase chain reaction (qPCR) and flow cytometry in the sample of peripheral blood.

Full Information

First Posted
November 22, 2022
Last Updated
June 16, 2023
Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
University Cancer Research Fund at Lineberger Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT05634785
Brief Title
CD30 CAR for CD30+ NSGCT
Official Title
Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Patients With CD30+ Nonseminomatous Germ Cell Tumors (NSGCT)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 9, 2022 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNC Lineberger Comprehensive Cancer Center
Collaborators
University Cancer Research Fund at Lineberger Comprehensive Cancer Center

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 2 research study that enrolls adult subjects with Nonseminomatous Germ Cell Tumors (NSGCT). The purpose of this study is to create a repository and explore the presence of modified T cells in the subject's plasma or tumors. This study collects biospecimens (such as tumor tissue, blood, and modified T cells) that can be used in future research studies. The collected specimens can help to examine whether the modified T cells are present in the body and tumor. If the modified T cells are present in the body, and how long they last. They also will use the specimen to identify ways to improve treatment options for a future cancer patient. Research with blood, tissue, or body fluids (specimens) can help researchers understand how the human body works. Sometimes researchers collect and store specimens and use them for different kinds of research or share them with other scientists; this is called a specimen repository or "biobank." Research with biospecimens might help to introduce new tests to find diseases or new ways to treat diseases. The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding those bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to cure most patients. This study is designed to combine both T cells and antibodies to create a more effective treatment called autologous T lymphocyte chimeric antigen receptor cells targeted against the CD30 antigen (ATLCAR.CD30) administration. Prior trials have shown the safety of ATLCAR.CD30 product was administered to subjects with lymphomas. This study was planned based on the safety and efficacy data from previous studies (NCT02690545 and NCT02917083).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Germ Cell Tumor, Nonseminomatous Germ Cell Tumor
Keywords
cellular therapy, modified T cells, ATLCAR.CD30, biobank, repository, specimen

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ATLCAR.CD30
Arm Type
Experimental
Arm Description
Single Group Assignment: Subjects with Nonseminomatous Germ Cell Tumors who meet eligibility criteria for cellular therapy.
Intervention Type
Biological
Intervention Name(s)
ATLCAR.CD30 Cells
Other Intervention Name(s)
CAR.CD30 T cells
Intervention Description
The cellular product consists of ATLCAR.CD30 cells will be administered via intravenous injection, over 5 - 10 minutes after lymphodepletion. The expected volume will be 1 - 50 mL, the prescribed dose will be 2 × 108 CAR-T cells per meter square and the maximum dose will be 5 × 108 CAR-T cells per meter square.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamid
Other Intervention Name(s)
Cytoxan
Intervention Description
Two to 14 days prior to the initial ATLCAR.CD30 infusion, subjects will receive a lymphodepletion regimen that includes 300 mg per square meter of intravenous cyclophosphamide.
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Other Intervention Name(s)
Fludara
Intervention Description
Two to 14 days prior to the initial ATLCAR.CD30 infusion, subjects will receive a lymphodepletion regimen that includes daily 30 mg per square meter of intravenous fludarabine infusion for 3 days.
Primary Outcome Measure Information:
Title
The Overall response rate (ORR)- Response Evaluation Criteria In Solid Tumors Criteria (RECIST)
Description
ORR - RECIST will be assessed per RECIST v1.1. criteria which define Complete Response (CR) as the disappearance of all target lesions, pathological lymph node (LN) <10mm, and normalization of serum tumor markers; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions serum tumor markers (AFP and β-hCG) should be stable or decreasing. ; and Overall Response Rate (ORR) = CR + PR/total number of subjects.
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
The Overall response rate (ORR)- Per immune-related Response Evaluation Criteria (irRECIST)
Description
ORR -irRECIST will be assessed per irRECIST criteria which defines complete response (irCR), the disappearance of all lesions, no new lesions, lymph nodes < 10 mm in short axis; partial response (irPR), ≥30% decrease in the sum of target lesions and non-target lesions are irNN; Stable response (irSD), not meeting criteria for irCR, irPR, or irPD; Progressive Disease (irPD), ≥20% increase in tumor burden and minimum 5 mm absolute increase in compared to nadir; for no new non-target or (irNN) and where irPR or irPD are confirmed by a repeat, consecutive assessment.
Time Frame
Up to 6 weeks
Title
The best overall response rate (BORR)
Description
BORR will be defined as the best response recorded after the administration of the cell therapy to the date of disease progression per modified RECIST 1.1, or death as a result of any cause.
Time Frame
Up to 6 weeks
Title
Progression free survival (PFS)
Description
PFS will be defined per modified RECIST 1.1 criteria. PFS is defined from the day of ATLCAR.CD30 infusion to relapse (in patients with a documented complete response at the time of cell infusion) or progression (in patients without a complete response at the time of cell infusion), or death as a result of any cause per modified RECIST 1.1 criteria classification.
Time Frame
Up to12 weeks
Title
Median Progression free survival (PFS)
Description
Median PFS is defined from the day of initial lymphodepletion administration of the first ATLCAR.CD30 product infusion to the date of disease progression per modified RECIST 1.1 criteria or death as a result of any cause.
Time Frame
Up to12 weeks
Title
Duration of response (DOR)
Description
DOR will be defined as the time from documentation of PR or better to PD as defined by modified RECIST 1.1 criteria. Progressive Disease (PD) - At least a 20% increase in the sum of the longest diameter (LD) of the target lesions, a relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm or the appearance of one or more new lesion or unequivocal progression of non-target or non-measurable lesions (e.g. worsening bone pain requiring radiation or significant increase in pain medications) or increase ≥ 50% in AFP or β-hCG.
Time Frame
Up to12 weeks
Title
The percentage of improvement
Description
The percentage of subjects who have an improvement in their response per modified RECIST 1.1.
Time Frame
Up to 12 weeks
Title
Adverse Events CTCAE
Description
Adverse Events CTCAE will be classified and graded according to the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Time Frame
Up to 6 weeks
Title
Cytokine Release Syndrome (CRS)
Description
Cytokine Release Syndrome (CRS) will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) CRS Consensus Grading. Grade 1 - Mild (Symptomatic Management): Fever ≥38oC, No hypotension, No hypoxia, Grade 2 - Moderate (Moderate Intervention): Fever ≥38oC, Hypotension not requiring vasopressors, Hypoxia requiring low-flow nasal cannula (≤6 L/minute) or blow-by, Grade 3 - Severe (Aggressive Intervention): Fever ≥38oC , Hypotension requiring a vasopressor with or without vasopressin, Hypoxia requiring high-flow nasal cannula (>6 L/minute), facemask, nonrebreather mask, or Venturi mask, Grade 4 - Life-threatening (Life-sustaining intervention): Fever ≥38oC, Hypotension requiring multiple vasopressors (excluding vasopressin), Hypoxia requiring positive pressure (e.g., continuous positive airway pressure (CPAP), BiPAP, intubation, mechanical ventilation), Grade 5 - Death: Death.
Time Frame
Up to 6 weeks
Title
Immune effector cell-associated neurotoxicity syndrome (ICANS)
Description
Immune effector cell-associated neurotoxicity syndrome (ICANS) symptoms will be graded according to the criteria outlined in the protocol on a scale from 1 (mild) to 4 (critical). Cytokine release syndrome (CRS) will be graded according to criteria outlined in the protocol on a scale from 1 (mild) to grade 5 (death).
Time Frame
Up to 6 weeks
Title
Overall survival
Description
Overall survival will be defined from the day of initial lymphodepletion for the first administration ATLCAR.CD30 cells to date of death.
Time Frame
Up to 5 years
Title
Persistence and expansion of ATLCAR.CD30
Description
Persistence and expansion of ATLCAR.CD30 in peripheral blood will be determined by quantitative polymerase chain reaction (qPCR) and flow cytometry in the sample of peripheral blood.
Time Frame
Up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for the release of personal health information explained to, understood by, and signed by the subject or legally authorized representative. Age ≥ 18 years at the time of consent. Histologically confirmed diagnosis of Nonseminomatous Germ Cell Tumors (NSGCT) of any primary site. Subjects must have received at least one prior line of therapy for their NSGCT and meet one of the following criteria. There is no maximum number of prior lines of treatment allowed. Evidence of progressive or recurrent NSGCT after prior high-dose chemotherapy (HDCT) treatment, defined as meeting at least one of the following criteria: i. Tumor biopsy of new or growing or unresectable lesions demonstrating viable NSGCT. In the event of an incomplete gross resection where viable NSGCT is found, subjects will be considered eligible for the study. ii. Consecutive elevated serum tumor markers (β-HCG or AFP) are increasing. An increase of elevated lactate dehydrogenase (LDH) alone does not constitute progressive disease. iii. Development of new or enlarging lesions in the setting of persistently elevated β-HCG or AFP, even if the β-HCG and AFP are not continuing to rise. Exclusion Criteria: Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated in the study). Active infection with HIV, human T-cell leukemia virus, hepatitis B virus, and hepatitis C virus (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibodies or PCR negative for HTLV1 and 2, negative for Hepatitis B surface antigen, and negative for HCV antibody or HCV viral load.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catherine Cheng
Phone
919-445-4208
Email
catherine_cheng@med.unc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Babinec
Phone
919-962-7426
Email
caroline_babinec@med.unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew I Milowsky
Organizational Affiliation
UNC Lineberger Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Lineberger Comprehensive Cancer Center at University of North Carolina, Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Cheng
Phone
919-445-4208
Email
catherine_cheng@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Caroline Babinec
Phone
919-962-7426
Email
caroline_babinec@med.unc.edu
First Name & Middle Initial & Last Name & Degree
Matthew Milowsky, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://unclineberger.org/patientcare/clinical-trials/clinical-trials
Description
University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

Learn more about this trial

CD30 CAR for CD30+ NSGCT

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