Recruiting

A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients

0 criteria met from your profileSee at a glance how your profile meets each eligibility criteria.
What is being tested

Cyclophosphamide

+ Fludarabine
+ Anti-KRAS G12V mTCR PBL
Drug
Biological
Who is being recruted

Colonic Diseases
+16

+ Colonic Neoplasms
+ Digestive System Diseases
From 18 to 72 Years
+11 Eligibility Criteria
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 1 & 2
Interventional
Study Start: September 2017
See protocol details

Summary

Principal SponsorNational Cancer Institute (NCI)
Study ContactNCI SB Immunotherapy Recruitment Center
Last updated: January 18, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: September 21, 2017Actual date on which the first participant was enrolled.

Background: * We generated an HLA-A\*11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12V-mutated variant of KRAS (and other RAS family genes), expressed by many human cancers and constructed a single retroviral vector that contains alpha and beta chains that confer recognition of this antigen when transduced into PBL. * In co-cultures with HLA-A\*11:01+ target cells expressing this mutated oncogene, mTCR transduced T cells lyse target cells and secrete IFN-gamma with high specificity. Objectives: Primary objectives: * Phase I: Determine the safety of administering PBL transduced with anti-KRAS G12V mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2; aldesleukin). * Phase II: Determine if anti-KRAS G12V mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12V mutation. Eligibility: Patients must be/have: * Age greater than or equal to 18 years and less than or equal to 72 years * HLA-A\*11:01 positive * Metastatic or unresectable RAS G12V-expressing cancer which has progressed after standard therapy (if available). Patients may not have: -Allergies or hypersensitivities to high-dose aldesleukin, cyclophosphamide or fludarabine. Design: * This is a Phase I/II, single center study of PBL transduced with anti-KRAS G12V mTCR in HLA-A\*11:01 positive patients with advanced solid tumors expressing G12V mutated RAS. * PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth. * Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-KRAS G12V mTCR. * All patients will receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine. * On day 0, patients will receive their PBL transduced with the anti-KRAS G12V mTCR and will then begin high-dose aldesleukin. * A complete evaluation of lesions will be conducted approximately 6 weeks (+/- 2 weeks) after treatment. * The study will be conducted using a phase I/II Simon minimax design, with two separate cohorts for the Phase II component: Cohort 2a, patients with RAS G12V pancreatic cancer, and Cohort 2b, patients with RAS G12V non-pancreatic cancer. -A total of up to 110 patients may be required; approximately 24 patients in the phase I portion of the study and 86 (41, plus an allowance of up to 2 non-evaluable per phase II cohort) patients in the phase II portion of the study.

Official TitleA Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients 
NCT03190941
Principal SponsorNational Cancer Institute (NCI)
Study ContactNCI SB Immunotherapy Recruitment Center
Last updated: January 18, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
110 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are assigned to groups based on specific criteria, such as their medical history or a doctor's recommendation. This approach ensures that treatments are given to those who may benefit the most, based on known factors.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
None (Single-arm trial): If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants receive treatments one after another in a pre-planned sequence. The next treatment may depend on how the participant responds to the previous one.

Other Ways to Assign Treatments
Single-group assignment: Everyone gets the same treatment.
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 18 to 72 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Colonic Diseases
Colonic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Pancreatic Neoplasms
Rectal Diseases
Rectal Neoplasms
Stomach Diseases
Stomach Neoplasms
Colorectal Neoplasms
Criteria
11 exclusion criteria prevent from participating
Large volume pulmonary irradiation.
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
Concurrent systemic steroid therapy.
Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

Show More Criteria

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-KRAS G12V mTCR PBL + high-dose aldesleukin

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum 9 doses).
Group II
Experimental
Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-KRAS G12V mTCR PBL + high-dose aldesleukin

Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

Days -7 to -3: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.

Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum 9 doses).
Study Objectives
Primary Objectives

Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)

Grade and type of toxicity per dose level; fraction of patients who experience a DLT at a given dose level, and number and grade of each type of DLT

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Recruiting
National Institutes of Health Clinical CenterBethesda, United StatesSee the location
Recruiting
One Study Center
;