Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome

Summary

This phase I trial tests the side effects and best dose of total marrow lymphoid irradiation along with chemotherapy, with fludarabine and melphalan, with or without thiotepa, in combination with Orca-T cells for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS). Total marrow and lymphoid irradiation is a targeted form of total body irradiation that uses intensity-modulated radiation therapy to target marrow, lymph node chains, and the spleen. It is designed to reduce radiation-associated side effects and maximize the radiation therapeutic effect. Giving chemotherapy with medications such as thiotepa, fludarabine, and melphalan before a treatment with stem cells helps kill cancer cells in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. Orca-T cells take cells from a donor and remove some of the T cells and replace them with partially engineered T cells in order to induce better tolerance in patients. Giving total marrow and lymphoid irradiation and chemotherapy followed by Orca -T cells may be an effective treatment for patients with AML, ALL or MDS.

Conditions

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Myelodysplastic Syndrome

Interventions

PROCEDURE

Biospecimen Collection

Undergo blood sample collection

PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

PROCEDURE

Bone Marrow Biopsy

Undergo bone marrow biopsy

PROCEDURE

Dual-Energy Computed Tomography

Undergo DECT/MRI scan

PROCEDURE

Echocardiography

Undergo echocardiography

DRUG

Fludarabine

Given IV

PROCEDURE

Magnetic Resonance Imaging

Undergo DECT/MRI scan

DRUG

Melphalan

Given IV

PROCEDURE

Multigated Acquisition Scan

Undergo MUGA scan

BIOLOGICAL

Partially Engineered T-regulatory Cell Donor Graft TRGFT-201

Given IV

DRUG

Tacrolimus

Given tacrolimus

DRUG

Thiotepa

Given IV

RADIATION

Total Marrow and Lymphoid Irradiation

Undergo TMLI

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• City of Hope Medical Center

  lead OTHER

Principal Investigators

• Amandeep Salhotra · City of Hope Medical Center

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-05-24

Primary Completion

2030-03-22

Completion

2030-03-22

FDA Drug

Yes

Countries

• United States

Study Locations