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
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.
• 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 flow cytometry at screening.
• Must be ineligible for or unwilling to undergo allogeneic stem cell transplant (SCT).
• Clinical performance status (PS): Karnofsky \>= 50% (participants \>= 16 years of age), or Lansky scale \>= 50% (participants \< 16 years of age). Participants who are unable to walk because of paralysis, but who are upright in a wheelchair may be considered eligible.
• Must have no ongoing signs of CRS from prior CAR T cell infusion and/or ICANs at screening.
• Participants must have adequate organ function as defined below:
‣ Total bilirubin \<= 2 x institutional upper limit of normal (ULN)
⁃ Aspartate Aminotransferase (AST) \<= 10 x ULN
⁃ Alanine Aminotransferase (ALT) \<= 10 x ULN
⁃ creatinine \<= the maximum for age listed below OR measured creatinine clearance \>= 60 mL/min/1.73 m\^2 for participants with
∙ creatinine levels above the max
• Age: \<=5, Maximum Serum, Creatinine \<= .8 mg/dL
• Age: \>5 to \<=10, Maximum Serum, Creatinine \<= 1.0mg/dL
• Age: \>10, Maximum Serum, Creatinine \<= 1.2mg/dL
‣ A participant may have continued to expect CAR T cell-associated cytopenias of any grade.
⁃ Cardiac function: left ventricular ejection fraction\>= 45% or fractional shortening \>= 28%.
⁃ Pulmonary function: baseline oxygen saturation \>= 92% on room air; participants with respiratory symptoms (e.g., dyspnea, hypoxia \<92%) must have a diffusing capacity of the lungs for carbon monoxide (DLCO)/adjusted \> 45%.
⁃ Women of childbearing potential (WOCBP) must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy.
∙ Note: WOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal.
∙ Men able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 7 months after the last dose of study drugs. We also will recommend men ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Individuals able to father a child must not freeze or donate sperm within the same period.
• Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study drug(s).
• Participants must be enrolled on protocol 15-C-0028, Follow-Up Evaluation for Gene- Therapy Related Delayed Adverse Events after Participation in Pediatric Oncology Branch Clinical Trials.
• Ability of participant or /Legally Authorized Representative (LAR) to understand and be willing to sign a written informed consent document.