CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory CD19/CD22-expressing B Cell Malignancies

Summary

Background:

B-cell leukemias and lymphomas are cancers that are often difficult to treat. The primary objective of this study is to determine the ability to take a patient's own cells (T lymphocytes) and grow them in the laboratory with the cluster of differentiation 19 (CD19/cluster of differentiation 22-chimeric antigen receptor (CD22-CAR) gene through a process called 'lentiviral transduction (also considered gene therapy) and growing them to large numbers to use as a treatment for hematologic cancers in children and young adults.. Researchers want to see if giving modified CD19/CD22-CAR T cells to people with these cancers can attack cancer cells. In addition, the safety of giving these gene modified cells to humans will be tested at different cell doses. Additional objectives are to determine if this therapy can cause regression of B cell cancers and to measure if the gene modified cells survive in patients' blood.

Objective:

To study the safety and effects of giving CD19/CD22-CAR T cells to children and young adults with B-cell cancer.

Eligibility:

People ages 3-39 with certain cancers that have not been cured by standard therapy. Their cancer tissue must express the CD19 protein.

Design:

A sample of participants blood or bone marrow will be sent to National Institutes of Health (NIH) and tested for leukemia.

Participants will be screened with:

Medical history

Physical exam

Urine and blood tests (including for human immunodeficiency virus (HIV)

Heart and eye tests

Neurologic assessment and symptom checklist.

Scans, bone marrow biopsy, and/or spinal tap

Some participants will have lung tests.

Participants will repeat these tests throughout the study and follow-up.

Participants will have leukapheresis. Blood will be drawn from a plastic tube (intravenous (IV) or needle in one arm then go through a machine that removes lymphocytes. The remaining blood will be returned to the participant's other arm.

Participants will stay in the hospital about 2 weeks. There they will get:

Two chemotherapy drugs by IV

Their changed cells by IV

Standard drugs for side effects

Participants will have frequent follow-up visits for 1 year, then 5 visits for the next 4 years. Then they will answer questions and have blood tests every year for 15 years.

...

Conditions

• Lymphoma, Non-Hodgkin
• Leukemia, Lymphocytic, B Cell
• B-Cell Lymphoma
• B-Cell Leukemia
• Acute Lymphoid Leukemia
• B-Non Hodgkin Lymphoma
• B-NHL
• B-All
• Acute Lymphoblastic Leukemia
• Acute Lymphocytic Leukemia

Interventions

BIOLOGICAL

CD19/CD22 CAR T-Cells

Cluster of differentiation 19 (CD19)/cluster of differentiation 22 (CD22) chimeric antigen receptor (CAR) T-cells will be infused on Day 0 after lymphodepleting chemotherapy regimen.

DRUG

Fludarabine

Fludarabine is administered as an intravenous (IV) infusion in an appropriate solution over 30 minutes. To prevent undue toxicity the dose will be based on body surface area (BSA) (25-30 mg/m\^2/dose) on Days -4, -3, -2 or Days -5, -4, -3, -2.

DRUG

Cyclophosphamide

Cyclophosphamide will be diluted in an appropriate solution and infused over one hour. The dose will be based on the body surface area (BSA), at 900 mg/m\^2/dose after fludarabine infusion on Day -2 or 600 mg/m\^2/dose on Days -3 \& -2.

PROCEDURE

Apheresis

According to institutional standards.

OTHER

Anti-emetic

Prophylaxis and treatment.

DRUG

Diphenhydramine

Pre-medication: 0.5-1 mg/kg/dose (maximum 50 mg/dose) by mouth or intravenous over 10-15 minutes.

DRUG

Acetaminophen

Pre-medication: 15 mg/kg/dose (maximum 650 mg/dose by mouth).

DIAGNOSTIC_TEST

ECG

Pre-cell infusion.

DIAGNOSTIC_TEST

ECHO

Pre-cell infusion.

DIAGNOSTIC_TEST

MRI Brain

Pre-cell infusion.

PROCEDURE

Bone marrow biopsy

Pre-cell infusion.

DIAGNOSTIC_TEST

Cardiac MRI

Screening

Sponsors & Collaborators

• National Cancer Institute (NCI)

  lead NIH

Principal Investigators

• Nirali N Shah, M.D. · National Cancer Institute (NCI)

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

3 Years

Max Age

39 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-03-26

Primary Completion

2024-07-10

Completion

2025-01-13

FDA Drug

Yes

Countries

• United States

Study Locations