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

Summary

Background:

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. About 90% of children and young adults who are treated for ALL can now be cured. But if the disease comes back, the survival rate drops to less than 50%. Better treatments are needed for ALL relapses.

Objective:

To test chimeric antigen receptor (CAR) therapy. CARs are genetically modified cells created from each patient s own blood cells. his trial will use a new type of CAR T-cell that is targeting both CD19 and CD22 at the same time. CD19 and CD22 are proteins found on the surface of most types of ALL.

Eligibility:

People aged 3 to 39 with ALL or related B-cell lymphoma that has not been cured by standard therapy.

Design:

Participants will be screened. This will include:

Physical exam

Blood and urine tests

Tests of their lung and heart function

Imaging scans

Bone marrow biopsy. A large needle will be inserted into the body to draw some tissues from the interior of a bone.

Lumbar puncture. A needle will be inserted into the lower back to draw fluid from the area around the spinal cord.

Participants will undergo apheresis. Their blood will circulate through a machine that separates blood into different parts. The portion containing T cells will be collected; the remaining cells and fluids will be returned to the body. The T cells will be changed in a laboratory to make them better at fighting cancer cells.

Participants will receive chemotherapy starting 4 or 5 days before the CAR treatment.

Participants will be admitted to the hospital. Their own modified T cells will be returned to their body.

Participants will visit the clinic 2 times a week for 28 days after treatment. Follow-up will continue for 15 years....

Conditions

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

Interventions

BIOLOGICAL

CD19/CD22-CAR-transduced T cells

CD19/CD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen

DRUG

cyclophosphamide

Cyclophosphamide will be diluted in an appropriate solution and infused over one hour. The dose will be based on the patient s body weight, at 900 mg/m2/dose after fludarabine infusion.

DRUG

fludarabine

Fludarabine is administered as an IV infusion in an appropriate solution over 30 minutes. To prevent undue toxicity the dose will be based on BSA (25 mg/m2/dose).

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

PARALLEL

Eligibility

Min Age

3 Years

Max Age

39 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2022-12-28

Primary Completion

2027-07-01

Completion

2029-07-01

FDA Drug

Yes

Countries

• United States

Study Locations