TCR-Transduced T Cells for Blood Cancers

Overseen By Genevieve C Fromm

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 0

86 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Research Team

James N Kochenderfer, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

This trial is for adults aged 18 to 75 with one of nine specific blood cancers, including various leukemias and myelodysplastic syndromes. Participants must have a confirmed diagnosis with TP53 or RAS mutations. They should be able to undergo procedures like bone marrow biopsy and apheresis.

Inclusion Criteria

-Eligible diagnoses include AML (acute myeloid leukemia), MDS (myelodysplastic syndrome), CMML(chronic myelomonocytic leukemia), CML (chronic myeloid leukemia), and T-ALL (T-acute lymphoblastic leukemia/lymphoma) meeting standard diagnostic criteria as described in the 5th edition World Health Organization Classification of Hematologic Tumors and/or the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias. Multiple myeloma participants meeting International Working Group diagnostic criteria are eligible. These diagnostic criteria can be met at any time during the course of the participant s malignancy. Atypical CML is not an eligible diagnosis.

NOTE: Pathology reports are acceptable to confirm eligibility.

* Detection of at least one of the neoepitope-forming TP53 or RAS mutations that are listed in Table 3 in on the TruSight Oncology (TSO) 500 sequencing panel (NSR device) performed in the NCI Laboratory of Pathology is required. RAS mutations can be in NRAS, KRAS or HRAS as these oncogenes have the same amino acid sequence at the location of the targeted neoepitopes. A variant allele frequency (VAF) of at least 5% is required for a mutation to be eligible. This criterion can be met at any time within 60 days prior to apheresis regardless of treatment history during this 60-day period. DNA for sequencing comes from bone marrow.

Treatment Details

Interventions

• Individual Patient TCR-Transduced PBL

Trial Overview The study tests altering T cells to target cancer-specific substances called neoepitopes in blood cancers. It involves taking the patient's T cells, modifying them in the lab, then reintroducing them after pre-treatment drugs are administered over three days.

Participant Groups

Group I: 2/Experimental: prior allo-HSCT Experimental Treatment 5 Interventions

Preparative regimen of cyclophosphamide and fludarabine + infusion of neoepitope-specific T cells (at a dose of 1x10\^10 total cells) + aldesleukin.

Group II: 1/Experimental: No allo-HSCT Experimental Treatment 5 Interventions

Preparative regimen of cyclophosphamide and fludarabine + infusion of neoepitope-specific T cells (of up to 1.5x10\^11 total cells) + aldesleukin.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+