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

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-120
SponsorNational Cancer Institute (NCI)

About 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.

Eligibility criteria

Qualifiers

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.

Presence of the correct HLA type needed to present one of the targeted neoepitopes as shown in Table 3. HLA typing data from any time-point prior to apheresis can be used to meet this requirement.

For AML and MDS, bone marrow myeloblast percentage must be >=5% of nucleated cells in either bone marrow aspirate or biopsy. Myeloblasts can be defined by immunohistochemistry or by cytochemistry stains including but not limited to myeloperoxidase.

For T-ALL, bone marrow T-cell blast percentage must be >=5% of nucleated cells in either bone marrow aspirate or biopsy. T cells can be defined by cytochemistry or immunohistochemistry or flow cytometry.

Disqualifiers

Corticosteroids given for any indication at doses greater than 5 mg/day of prednisone or equivalent within 14 days before either apheresis or start of protocol chemotherapy.

Participants with MDS/Myeloproliferative neoplasia overlap syndromes are not eligible.

Participants with acute promyelocytic leukemia are not eligible.

Participants who received a mis-matched sibling or haploidentical transplant are not eligible.

Trial design

Treatments tested in this trial

  • aldesleukin
  • cyclophosphamide
  • fludarabine phosphate
  • Individual Patient TCR-Transduced PBL
  • TruSight Oncology (TSO) 500

Treatment groups

86 Participants
are divided into 2 treatment groups