RECRUITING

Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients

Conditions

Gastrointestinal Cancer Pancreatic Cancer Gastric Cancer Colon Cancer Rectal Cancer Immunotherapy Cell Therapy KRAS HRAS NRAS

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: A new cancer therapy takes white blood cells from a person, grows them in a lab, genetically changes them, then gives them back to the person. Researchers think this may help attack tumors in people with certain cancers. It is called gene transfer using anti-KRAS G12D mTCR cells. Objective: To see if anti-KRAS G12D mTCR cells are safe and cause tumors to shrink. Eligibility: Adults ages 18-72 who have cancer with a molecule on the tumors that can be recognized by the study cells Design: Participants will be screened with medical history, physical exam, scans, photography, and heart, lung, and lab tests. An intravenous (IV) catheter will be placed in a large vein in the chest. Participants will have leukapheresis. Blood will be removed through a needle in an arm. A machine will divide the blood and collect white blood cells. The rest of the blood will be returned to the participant through a needle in the other arm. A few weeks later, participants will have a hospital stay. They will: * Get 2 chemotherapy medicines by IV over 5 days. * Get the changed cells through the catheter. Get up to 9 doses of a medicine to help the cells. They may get a shot to stimulate blood cells. * Recover in the hospital for up to 3 weeks. They will provide blood samples. Participants will take an antibiotic for at least 6 months. Participants will have several follow-up visits over 2 years. They will repeat most of the screening tests and may have leukapheresis. Participants blood will be collected for several years.

Official Title

A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients

Quick Facts

Study Start:2019-05-16

Study Completion:2028-12-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03745326

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 72 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Measurable (per RECIST v1.1 criteria), metastatic, or unresectable malignancy expressing G12D mutated KRAS as assessed by one of the following methods: RT-PCR on tumor tissue, tumor DNA sequencing, or any other CLIA-certified laboratory test on 2. Patients must be HLA-A\11:01 positive as confirmed by the NIH Department of Transfusion Medicine. 3. Confirmation of the diagnosis of cancer by the NCI Laboratory of Pathology. 4. Patients must have: Patients with metastatic colorectal cancer must have had at least two systemic chemotherapy regimens that include 5FU, leucovorin, bevacizumab, oxaliplatin, and irinotecan (or similar agents), or have contraindications to receiving those medications. * Patients with pancreatic cancer must have received gemcitabine, 5FU, and oxaliplatin (or similar agents), or have contraindications to receiving those medications. * Patients with non-small cell lung cancer (NSCLC) must have had appropriate targeted therapy as indicated by abnormalities in ALK, EGFR, or expression of PDL-1. Other patients must have had platinum-based chemotherapy. * Patients with ovarian cancer or prostate cancer must have had approved first-line chemotherapy. 5. Patients with 3 or fewer brain metastases that are \< 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with 6. Age greater than or equal to 18 years and less than or equal to 72 years. 7. Clinical performance status of ECOG 0 or 1 8. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for 12 months after the last dose of combined chemotherapy for women and for four months after treatment for men. 9. Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus. 10. Serology 11. Hematology * ANC \> 1000/mm\^3 without the support of filgrastim * WBC greater than or equal to 2500/mm\^3 * Platelet count greater than or equal to 80,000/mm\^3 * Hemoglobin \> 8.0 g/dL. Subjects may be transfused to reach this cut-off. 12. Chemistry * Serum ALT/AST less than or equal to 5.0 x ULN * Serum creatinine less than or equal to 1.6 mg/dL * Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL. 13. Patients must have completed any prior systemic therapy at the time of enrollment. 14. Ability of subject to understand and the willingness to sign a written informed consent document. 15. Willing to sign a durable power of attorney. 16. Subjects must be co-enrolled on the protocol 03C0277.	1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. 2. Concurrent systemic steroid therapy. 3. Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses. 4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). 5. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.) 6. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin. 7. History of coronary revascularization or ischemic symptoms. 8. For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.

Inclusion Criteria

Exclusion Criteria

1. Measurable (per RECIST v1.1 criteria), metastatic, or unresectable malignancy expressing G12D mutated KRAS as assessed by one of the following methods: RT-PCR on tumor tissue, tumor DNA sequencing, or any other CLIA-certified laboratory test on
2. Patients must be HLA-A\*11:01 positive as confirmed by the NIH Department of Transfusion Medicine.
3. Confirmation of the diagnosis of cancer by the NCI Laboratory of Pathology.
4. Patients must have:
* Patients with metastatic colorectal cancer must have had at least two systemic chemotherapy regimens that include 5FU, leucovorin, bevacizumab, oxaliplatin, and irinotecan (or similar agents), or have contraindications to receiving those medications.
* Patients with pancreatic cancer must have received gemcitabine, 5FU, and oxaliplatin (or similar agents), or have contraindications to receiving those medications.
* Patients with non-small cell lung cancer (NSCLC) must have had appropriate targeted therapy as indicated by abnormalities in ALK, EGFR, or expression of PDL-1. Other patients must have had platinum-based chemotherapy.
* Patients with ovarian cancer or prostate cancer must have had approved first-line chemotherapy.
5. Patients with 3 or fewer brain metastases that are \< 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with
6. Age greater than or equal to 18 years and less than or equal to 72 years.
7. Clinical performance status of ECOG 0 or 1
8. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for 12 months after the last dose of combined chemotherapy for women and for four months after treatment for men.
9. Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.
10. Serology
11. Hematology
* ANC \> 1000/mm\^3 without the support of filgrastim
* WBC greater than or equal to 2500/mm\^3
* Platelet count greater than or equal to 80,000/mm\^3
* Hemoglobin \> 8.0 g/dL. Subjects may be transfused to reach this cut-off.
12. Chemistry
* Serum ALT/AST less than or equal to 5.0 x ULN
* Serum creatinine less than or equal to 1.6 mg/dL
* Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL.
13. Patients must have completed any prior systemic therapy at the time of enrollment.
14. Ability of subject to understand and the willingness to sign a written informed consent document.
15. Willing to sign a durable power of attorney.
16. Subjects must be co-enrolled on the protocol 03C0277.

1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
2. Concurrent systemic steroid therapy.
3. Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
5. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
6. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
7. History of coronary revascularization or ischemic symptoms.
8. For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.

Contacts and Locations

Study Contact

NCI SB Immunotherapy Recruitment Center

CONTACT

(866) 820-4505

irc@nih.gov

James C Yang, M.D.

CONTACT

(240) 760-6223

jamesyang@mail.nih.gov

Principal Investigator

James C Yang, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

James C Yang, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-05-16

Study Completion Date2028-12-01

Study Record Updates

Study Start Date2019-05-16

Study Completion Date2028-12-01

Terms related to this study

Keywords Provided by Researchers

Immunotherapy
Cell Therapy
KRAS
HRAS
NRAS

Additional Relevant MeSH Terms

Gastrointestinal Cancer
Pancreatic Cancer
Gastric Cancer
Colon Cancer
Rectal Cancer