Actively Recruiting
A Phase I Study of Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Acute Myeloid Leukemia, Myelodysplastic Syndrome, and Other Hematologic Malignancies
Led by National Cancer Institute (NCI) · Updated on 2026-06-08
86
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying a treatment for certain blood cancers, including acute myeloid leukemia and myelodysplastic syndrome, that have mutations in the TP53 or RAS genes. These mutations can create unique markers called neoepitopes on cancer cells. The trial evaluates the use of specially modified T cells designed to target these neoepitopes, aiming to assess the safety of this approach combined with chemotherapy and aldesleukin in participants with these blood cancers. Participants undergo a bone marrow biopsy and skin biopsy to confirm their diagnosis and detect specific mutations. Their blood is collected through a process called apheresis to isolate T cells, which are then genetically modified to recognize neoepitopes. Before receiving the modified T cells through an intravenous infusion, participants are given chemotherapy drugs cyclophosphamide and fludarabine for three days. After infusion, participants receive aldesleukin infusions and remain hospitalized for at least seven days for close monitoring. During the first year after treatment, participants have eight follow-up visits, with six additional visits over the next four years. Long-term follow-up continues for ten years to monitor safety and response. Assessments include blood tests, bone marrow biopsies, and evaluations for treatment effects and side effects. Researchers measure safety from chemotherapy start through five years after T cell infusion as the primary outcome, along with response rates and feasibility of cell manufacturing.
CONDITIONS
Brief Title
Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Adults aged 18 to 75 years
- Diagnosed with AML, MDS, CMML, CML, T-ALL, or multiple myeloma meeting standard diagnostic criteria
- Malignant cells must have a TP53 or RAS mutation targeted by the study TCRs
- Must have the HLA type capable of presenting the targeted neoepitope
- Bone marrow or blood disease burden meeting specified thresholds
- No more than 1% circulating malignant cells before apheresis
- Willing to undergo intensive care if needed
- No systemic chemotherapy within 14 days before lymphodepleting chemotherapy or apheresis (with some exceptions)
- Recipients of fully matched alloHSCT allowed with no or mild graft-versus-host disease
- ECOG performance status 0 or 1
- Adequate organ function by specified laboratory tests
- Negative hepatitis B and C tests or controlled infection
- Cardiac ejection fraction ≥50% by echocardiogram
- Willing to undergo mandatory bone marrow biopsies
- Must agree to contraception requirements if applicable
- Willing to stay near clinical center during early post-treatment period
- Ability to understand and sign informed consent and durable power of attorney
You will not qualify if you...
- Use of systemic immunosuppressive drugs >5 mg/day prednisone or equivalent within 28 days before apheresis for alloHSCT recipients
- High-dose corticosteroids (>5 mg/day prednisone or equivalent) within 14 days before apheresis or chemotherapy
- Diagnosis of MDS/myeloproliferative overlap syndromes or acute promyelocytic leukemia
- History of mismatched or haploidentical transplant
- Tumor masses ≥10 cm in largest diameter
- Positive pregnancy test in women of childbearing potential
- Positive tests for HTLV-1/2, HIV infection
- Urgent therapy required due to tumor mass effects or tumor lysis syndrome
- Significant illness impairing treatment tolerance
- History of previous malignancy not in remission for at least 2 years or requiring recent treatment
- Active uncontrolled infections or fever >38°C without known cause
- Other conditions judged by investigator to impair study participation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 1 week including chemotherapy, cell infusion, and aldesleukin dosing
Participants receive a preparative chemotherapy regimen of cyclophosphamide and fludarabine, followed by an infusion of neoepitope-specific T cells targeting p53 or Ras mutations, and aldesleukin infusions to stimulate T-cell activity.
Daily visits for chemotherapy and aldesleukin infusions; 1 inpatient hospitalization immediately after T-cell infusion
Duration - Up to 5 years
Participants are monitored frequently as outpatients for toxicity and malignancy assessment after treatment completion.
Frequent outpatient visits for toxicity monitoring and disease assessment
Trial Site Locations
Total: 1 location
1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Actively Recruiting
Research Team
G
Genevieve C Fromm
J
James N Kochenderfer, M.D.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
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