DIRECT70: CAR T–Cell Therapy for Children with Blood Malignancies

Despite improvement in the outcomes of pediatric patients with newly diagnosed hematological malignancies, patients with relapsed or refractory disease still have poor outcomes with limited treatment options. Often, the response to salvage chemotherapy is poor, and the high rate of toxicities limits the use of more intense chemotherapy. New treatments are needed.

In this phase 1 clinical trial, we will use the patient’s T cells, modifying them in the lab to recognize and kill leukemia cells (CAR T cells). The study will contain 2-part eligibility criteria:

• One for apheresis and manufacturing of the CD70 CAR T cells
• A second to proceed with the infusion of CD70 CAR T cells.

A previously collected, cryopreserved leukapheresis product may also be used for manufacturing. The CAR T cells will be directed against the CD70 protein on the surface of cancer cells. The CD70 CAR T cells have the potential to kill cancer cells without harming normal blood-forming cells.

Treatment consists of a lymphodepleting chemotherapy regimen including fludarabine and cyclophosphamide followed by a single infusion of CD70 CAR T cells.

Primary objective

To determine the safety and maximum tolerated dose of intravenous infusions of escalating doses of CD70 CAR T cells in patients up to 21 years old with recurrent/refractory CD70+ hematological malignancies after lymphodepleting chemotherapy (fludarabine and cyclophosphamide).

Eligibility criteria

• Up to 21 years old
• CD70+ acute myeloid leukemia, acute lymphoblastic leukemia (B-ALL, T-ALL), lymphoma, or myelodysplastic syndrome
• If prior allogeneic hematopoietic cell transplant, no graft vs. host disease
• Has an identified hematopoietic cell transplantation (HCT) donor
• Has adequate organ function as detailed in the study

Exclusion criteria include:

• Immunodeficiency
• HIV-positive history
• Active infection
• Hypersensitivity to cornstarch or hydroxyethyl starch
• Acute promyelocytic leukemia (APL)
• Known problems with fludarabine/cyclophosphamide chemotherapy

Study site

St. Jude Children’s Research Hospital
Memphis, Tennessee

About this study

In recent years, there have been better outcomes for patients with newly diagnosed acute myeloid leukemia, acute lymphoblastic leukemia (B-ALL, T-ALL), lymphoma, and myelodysplastic syndrome. But patients whose disease has returned (relapsed or refractory) still have poor outcomes. Their treatment options are limited. They often respond poorly to chemotherapy and cannot get higher doses of chemotherapy. New treatments are needed.

The DIRECT70 clinical trial consists of these steps:

1. We will collect some of your child’s T cells. These cells are a type of immune system cell that can fight infection and kill cancer in the body. We may also use T cells that were already collected and frozen.
2. Once we have the T cells, we will change them in the lab so that they can recognize and kill cancer better. Cancer cells have a protein on their surface called CD-70. The patient’s new CAR-T cells (CD70+ CAR cells) will recognize this CD-70 protein “marker” on the cancer cells.
3. Then, your child will get chemotherapy treatment with medicines (fludarabine and cyclophosphamide) to kill cancer cells.
4. Next, we will give your child their own, new cancer-fighting CAR-T cells to kill any remaining cancer. These new CD70-CAR T cells may kill cancer cells without harming normal blood-forming cells.

Purpose of this clinical trial

The purpose of this study is to find the highest dose of CD70+ CAR cells that is safe to give to patients with CD70+ blood cancers. We will also study survival and side effects of patients who get chemotherapy and the CD70+ CAR cells.

Eligibility overview

Patients in the study must be 21 years old or younger and have:

• CD70+ acute myeloid leukemia, acute lymphoblastic leukemia (B-ALL, T-ALL), lymphoma, or myelodysplastic syndrome
• No graft vs. host disease from an earlier transplant
• An identified transplant donor
• Adequate organ function