Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT06904066
Phase
PHASE1
Status
Recruiting
Apply to this trial

Conditions

  • Blood Cancer
  • Dysmyelopoietic Syndromes
  • Hematological Neoplasms
  • Hematopoetic Myelodysplasia
  • Hematopoietic Malignancies
  • Leukemia, Lymphocytic, Acute
  • Malignancy, Hematologic
  • Myeloid Leukemia, Acute
  • Neoplasms, Hematologic
  • Neoplasms, Hematopoietic
  • Nonlymphoblastic Leukemia, Acute

Eligibility Criteria

Sex
ALL
Age
18 Years - 120 Years
Healthy Volunteers
Not accepted

Interventions

  • aldesleukin — DRUG
    Aldesleukin 600,000 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 4 days (maximum 10 doses).
  • cyclophosphamide — DRUG
    300 mg/m\^2 IV infusion over 30 minutes. Daily x 3 doses on days -5, -4, -3.
  • fludarabine phosphate — DRUG
    30 mg/m\^2 IV infusion over 30 minutes administered immediately following cyclophosphamide on day -5, -4, -3. Participants with renal dysfunction receive a lower dose of fludarabine.
  • Individual Patient TCR-Transduced PBL — BIOLOGICAL
    Up to 1.5x10\^11 total cells for non-transplant subjects. 1x10\^10 total cells for post-alloHSCT subjects.
  • TruSight Oncology (TSO) 500 — DEVICE
    TSO500 sequencing panel performed in the NCI Laboratory of Pathology to detect TP53 or RAS mutations

Study Details

Background: Blood cancers (such as leukemias) can be hard to treat, especially if they have mutations in the TP53 or RAS genes. These mutations can cause the cancer cells to create substances called neoepitopes. Researchers want to test a method of treating blood cancers by altering a person s T cells (a type of immune cell) to target neoepitopes. Objective: To test the use of neoepitope-specific T cells in people with blood cancers Eligibility: People aged 18 to 75 years with any of 9 blood cancers. Design: Participants will have a bone marrow biopsy: A sample of soft tissue will be removed from inside a pelvic bone. This is needed to confirm their diagnosis and the TP53 and RAS mutations in their cancer cells. They will also have a skin biopsy to look for these mutations in other tissue. Participants will undergo apheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein. The T cells will be grown to become neoepitope-specific T cells. Participants receive drugs for 3 days to prepare their body for the treatment. The modified T cells will be given through a tube inserted into a vein. Participants will need to remain in the clinic at least 7 days after treatment. Participants will have 8 follow-up visits in the first year after treatment. They will have 6 more visits over the next 4 years. Long-term follow-up will go on for 10 more years.

Key Dates

Start date
Jun 16, 2026
Status verified
May 2026
Primary completion
Apr 30, 2029
Completion
Apr 30, 2029

Study Design

Enrollment
86 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: 1/Experimental: No allo-HSCT
    Preparative regimen of cyclophosphamide and fludarabine + infusion of neoepitope-specific T cells (of up to 1.5x10\^11 total cells) + aldesleukin.
  • Experimental: 2/Experimental: prior allo-HSCT
    Preparative regimen of cyclophosphamide and fludarabine + infusion of neoepitope-specific T cells (at a dose of 1x10\^10 total cells) + aldesleukin.

Primary Outcome Measure

Safety [ Time Frame: From time of the lymphodepleting chemotherapy through 5 years after neoepitope-specific T cell infusion or until off study. ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892
NCI/Surgery Branch Recruitment Center
[email protected]
866-820-4505
Genevieve Fromm, RN
[email protected]
(240) 858-3663

Find similar trials in Bethesda, MD

By research site
National Institutes of Health Clinical Center· Bethesda, MD

Related Studies