Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

200 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-10-29

Study Completion Date

2029-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Objective:

To collect information on how often a solid tumor cancer might lose the Human Leukocyte Antigen (HLA) by next generation sequencing and perform apheresis to collect and store an eligible participant's own T cells for future use to make CAR T-Cell therapy for their disease treatment.

Design:

This is a non-interventional, observational study to evaluate participants with solid tumors with a high risk of relapse for incurable disease. No interventional therapy will be administered on this study. Some of the information regarding the participant's tumor analysis may be beneficial to management of their disease. Participants that meet all criteria may be enrolled and leukapheresed (blood cells collected). The participant's cells will be processed and stored for potential manufacture of CAR T-cell therapy upon relapse of their cancer.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Cell Selection for Bone Marrow Transplants to Prevent Graft-Versus-Host-Disease

NCT00001872

Graft vs Host Disease Hematologic Neoplasm

COMPLETED

Recruitment and Apheresis Collection of Peripheral Blood Hematopoietic Stem Cells, Mononuclear Cells and Granulocytes

NCT00001405

Granuloma Granulomatous Disease, Chronic Leukocyte Disease +2 more

RECRUITING

In-Vitro Studies in Depletion of Haplotype Mismatched Alloreactive T Cells

NCT00731705

Hematologic Malignancies Hematopoietic Stem Cell Transplantation

WITHDRAWN

Biospecimen Procurement for Immunological Landscape Studies Following Hematopoietic Cell Transplantation

NCT04428918

Hematopoietic Stem Cell Transplantation Cell Transplantation Hematologic Malignancies

WITHDRAWN

Immunologic Diagnostic Blood Test in Predicting Side-Effects in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Other Diseases

NCT00813501

Chronic Myeloproliferative Disorders Graft Versus Host Disease Infection +7 more

TERMINATED

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Background:

Human Leukocyte Antigen (HLA) is a protein on the outside of cells that allows the immune system to recognize it's own cells as normal and leave them alone or respond if infected with a virus or bacteria, or a tumor cell. HLA might not be expressed normally on cancer cells. This may be why cancer can grow undetected by the immune system and is referred to as a tumor escape mechanism. Tumor escape can occur for many reasons, but one reason is Loss of Heterozygosity (LOH). LOH is the loss of one of the genes that encodes HLA protein. A2 Biotherapeutics, Inc. (A2 Bio) is developing therapies to recognize, target, and kill cancer cells that do not express HLA normally, and minimize any damage to normal cells that express normal HLA.

Once participants are identified as having LOH on their tumors, apheresis, a procedure to separate and collect white blood cells will be performed. It is the first required step in manufacturing CAR T-cell therapy. The collected T cells will be stored for patients that are likely to benefit from CAR T-cell therapy during their disease care.

Study Design:

Approximately 1000 participants will be screened for part 1 of the study, including HLA typing, approximately 500 participants will have NGS testing on their tumor samples and be followed for up to 2 years on the study, and up to 200 participants will be screened for part 2 of the study and enrolled if eligible and apheresed and be followed for up to 2 years on the study.

Participants will be screened (Part 1) for HLA type, and based on results, participants will have archived tumor tissue tested by next generation sequencing (NGS) and be followed for up to 2 years. Based on the tumor NGS results, participants will be apheresed (Part 2) for Peripheral Blood Mononuclear Cell (PBMC) collection to store their T cells for a future interventional study upon relapse.

Each participant will proceed through the following study periods:

* Screening (Part 1 and 2)
* Enrollment (Apheresis)
* Post Apheresis safety follow-up (Day 7)
* Two-year long term follow-up

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Solid Tumor, Adult Colorectal Cancer Non Small Cell Lung Cancer Pancreatic Cancer CRC NSCLC Pancreas Cancer Mesothelioma Ovarian Cancer Ovarian Neoplasms Ovarian Carcinoma Mesothelioma, Malignant Mesothelioma; Lung Cancer Triple Negative Breast Cancer (TNBC) Renal Cell Carcinoma (Kidney Cancer) Head and Neck Squamous Cell Carcinoma HNSCC

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Apheresis

Apheresis procedure performed for collection of PBMCs.

Intervention Type OTHER

Next Generation Sequencing (NGS)

NGS on tumor tissue and a matched normal sample for loss of heterozygosity in tumor tissue and tumor tissue markers.

Intervention Type DIAGNOSTIC_TEST

Long Range NGS HLA typing

Long range NGS on whole blood to determine germline HLA type.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

1\. Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), or Pancreatic Cancer (PANC), that is metastatic, unresectable locally advanced, or in the Investigator's opinion the subject is high risk for incurable relapse within two years.

1. Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer (PANC), Mesothelioma, or Ovarian Cancer (OVAC) that is metastatic, unresectable locally advanced, or in the Investigator's opinion the subject is high risk for incurable relapse within two years.
2. Participants are germline HLA-A\*02 heterozygous confirmed by HLA typing.
3. Primary tumor tissue showing LOH of HLA-A\*02 by NGS testing.
4. Eastern Cooperative Oncology Group (ECOG) 0 or 1 performance status.

Exclusion Criteria

1. History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer.
2. Prior allogeneic stem cell transplant.
3. Prior solid organ transplant.

1. History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer.
2. Prior allogeneic stem cell transplant.
3. Prior solid organ transplant.
4. Participants who have received any cancer therapy on any investigational therapy for any indication, including but not limited to chemotherapy, small molecules, monoclonal antibodies, or radiotherapy (with bone marrow impact) within 2 weeks of planned apheresis or 3 half-lives, whichever is shorter.
5. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment necessitating specific treatment, or any major episode of infection requiring treatment with Intravenous (IV) antimicrobials (e.g., IV antibiotics) or hospitalization (relating to completion of antibiotic course).
6. Has known active central nervous system metastases. Subjects with previously treated brain metastases may participate upon medical monitor agreement.
7. In the Investigator's judgement, any other condition or reason the subject would not complete the required study visits and procedures, and follow up visits, or comply with the study requirements for participation.

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No