A Phase II Study to Examine the Impact of CD22 CAR T-cells to Extend the Duration of Remission Following Commercial CD19 CAR T-cells in Children, Adolescents, and Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
National Cancer Institute (NCI)
Summary
Background: Acute lymphoblastic leukemia (ALL) is a type of blood cancer. Chimeric antigen receptor (CAR) therapy involves taking immune cells (T cells) from a person and modifying them to better target cancer cells. CAR T-cell therapy that targets a marker called CD19 has been show to can cure ALL in many children and adults. But in about 50% of patients, the ALL comes back within a year. Researchers want to find out if a second treatment with CAR T-cell therapy that targets a different marker, CD22, can keep the cancer away longer. Objective: To see if CD22 CAR T-cell therapy can keep ALL away longer. Eligibility: People aged 3 to 65 years who have no signs of cancer after CD19 CAR T-cell treatment for ALL. Design: Participants will be screened. They will have imaging scans and tests of their heart function. A sample of tissue (biopsy) will be collected from their bone marrow. They will have a fluid sample collected from the area around their spinal cord. Participants will undergo collection of their white blood cells (T cells) during a procedure called leukapheresis. 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 cells will be altered in a lab to create CD22 CAR T-cell therapy. Participants will take drugs over 4 consecutive days to prepare their body for the CAR T-cell therapy; then they will receive their modified T cells through a tube inserted into a vein. Some people may need to stay in the hospital during treatment. Participants will have follow-up visits for 2 years.
Description
Background: * Despite impressive cure rates in children and young adults with B-cell acute lymphoblastic leukemia (B-ALL) generally, patients with relapsed/refractory disease have historically suffered from limited treatment options. CD19 and CD22 chimeric antigen receptor (CAR) T-cells are effective at inducing remission in the majority of children and young adults with relapsed/refractory B-ALL. * However, remissions are often not durable, and many patients will relapse in the absence of a consolidative hematopoietic stem cell transplant (HSCT), which is associated with high morbidity and m…
Eligibility
- Age range
- 3–65 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Participants must have documentation of pathologic confirmation of a diagnosis of relapsed/refractory B cell acute lymphoblastic leukemia (ALL). * History of CD19 and CD22 expression on malignant cells at diagnosis or relapse. * Age between \>= 3 years and \<= 65 years * Participants must have received an FDA-approved CD19 CAR T-cell construct for treatment of B cell ALL within the time period of \>= 2 months and \<= 7 months prior to apheresis or lymphodepleting (LD) (if apheresis is not done on this protocol). * Must be in an MRD-negative remission as demonstrated by…
Interventions
- BiologicalCD22 CAR-transduced T cells
CD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen
- DrugCyclophosphamide
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 500 mg/m\^2/dose after fludarabine infusion on days -3 and -2.
- DrugFludarabine
Fludarabine is administered as an IV infusion in an appropriate solution over 30 minutes on days -5 through -2. To prevent undue toxicity the dose will be based on BSA (30 mg/m\^2/dose).
Location
- National Institutes of Health Clinical CenterBethesda, Maryland