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

Summary

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.

Conditions

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

Interventions

DRUG

aldesleukin

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).

DRUG

cyclophosphamide

300 mg/m\^2 IV infusion over 30 minutes. Daily x 3 doses on days -5, -4, -3.

DRUG

fludarabine phosphate

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.

BIOLOGICAL

Individual Patient TCR-Transduced PBL

Up to 1.5x10\^11 total cells for non-transplant subjects. 1x10\^10 total cells for post-alloHSCT subjects.

DEVICE

TruSight Oncology (TSO) 500

TSO500 sequencing panel performed in the NCI Laboratory of Pathology to detect TP53 or RAS mutations

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• James N Kochenderfer, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

120 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-05-27

Primary Completion

2029-04-30

Completion

2029-04-30

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations