Using CD22 CAR T-cells to extend remission after commercial CD19 CAR T-cell therapy in children, adolescents, and adults with relapsed/refractory B‑ALL

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

This will try giving CD22-targeted CAR T-cells to people aged 3–65 who are in remission after CD19 CAR T-cell therapy to see if it helps keep their B-ALL from coming back longer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 3 Years to 65 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: CAR T, chemotherapy, Chimeric antigen receptor, cyclophosphamide, fludarabine
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT07328503 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-arm protocol enrolls patients aged 3–65 who are MRD-negative after receiving an FDA-approved CD19 CAR T-cell product. Eligible participants undergo screening (imaging, cardiac testing, bone marrow biopsy, and lumbar puncture) and receive lymphodepleting chemotherapy followed by infusion of autologous CD22 CAR T-cells. The primary endpoint is 1-year relapse-free survival, with serial monitoring for disease, CAR T-cell persistence, and treatment-related toxicities. The approach builds on prior CD22 and dual-antigen CAR strategies to attempt consolidation of CD19-induced remissions without immediate stem cell transplant.

Who should consider this trial

Good fit: Ideal candidates are people aged 3–65 who are in an MRD-negative remission after receiving an FDA-approved CD19 CAR T-cell therapy within the prior 2–7 months and who are ineligible for or decline allogeneic stem cell transplant.

Not a fit: Patients with active residual or relapsed disease, lack of CD22 expression on leukemia cells, outside the 2–7 month window after CD19 CAR T therapy, or who are planning for immediate transplant are unlikely to benefit from this consolidation approach.

Why it matters

Potential benefit: If successful, the approach could keep leukemia away longer and potentially reduce the need for allogeneic stem cell transplant.

How similar studies have performed: Prior phase 1/2 trials of CD22 CAR T-cells and co-infused or bicistronic CD19/CD22 CAR approaches have shown encouraging responses and manageable safety, though durable remissions remain a challenge.

Eligibility criteria

* 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 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.

EXCLUSION CRITERIA:

* Any central nervous system (CNS) involvement or signs of non-CNS extramedullary disease.
* Any active graft versus host disease (GVHD) in participants who are post-HSCT.
* Participants with disease recurrence requiring therapy post CD19 CAR. Note: Maintenance therapy post CD19 CAR (e.g., vincristine or tyrosine kinase inhibitor) for remission maintenance is allowed and will require a 1-week washout prior to apheresis or LD (if apheresis is not done on this protocol).
* Any investigational agent within 1 week before apheresis or LD (if apheresis is not done on this protocol).
* Pregnancy confirmed with beta-human chorionic gonadotropin (beta-HCG) serum or urine test performed at screening.
* Human immunodeficiency virus (HIV) infection, as measured by seropositivity for (HIV) antibody.
* Hepatitis B virus (HBV) infection, as measured by positivity for hepatitis B surface antigen (HBsAg).
* Hepatitis C virus (HCV) infection, as measured by seropositivity for hepatitis C.
* History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biological composition to any agent used in the study or in the manufacturing of cells.
* Uncontrolled, symptomatic intercurrent illness evaluated by medical history, physical exam, and/or laboratory testing, or social situation that would limit compliance with study requirements or would pose an unacceptable risk to the participant.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Sara K Silbert, M.D. — National Cancer Institute (NCI)
• Study coordinator: NCI Pediatric Leukemia, Lymphoma Transpl

Conditions Acute Lymphoblastic Leukemia; B-All; CD-22 Expressing Tumor; CD-19 expressing tumor; Adoptive Immunotherapy