CD22 CAR T-cells to Extend Remission Following Commercial CD19 CAR T-cells in Children, Adolescents, and Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

NCT07328503 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: 10001986001986-C
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Lymphoblastic Leukemia; B-All

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 1-year RFS (recurrence free survival)

  RFS of participants will be assessed by a Kaplan-Meier curve. The RFS probability and the median RFS will be reported along with 95% confidence intervals.

  1 year post cell infusion

Secondary Outcomes (5)

• 2-year RFS

  2 years post cell infusion

• 1-year and 2-year OS (overall survival)

  2 years post cell infusion

• Short-term safety

  28 days post cell infusion

• Long-term safety

  up to 2 years post cell infusion

• RFS from the time of additional CD22 CAR T-cell infusions

  up to 2 years post-cell infusion

Study Arms (1)

1

EXPERIMENTAL

Lymphodepleting chemotherapy followed by CD22 CAR T-cells

Biological: CD22 CAR-transduced T cells; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

CD22 CAR-transduced T cells BIOLOGICAL

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

1

Cyclophosphamide DRUG

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.

1

Fludarabine DRUG

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).

1

Eligibility Criteria

• Age: 3 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Sara K Silbert, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Pediatric Leukemia, Lymphoma Transpl

CONTACT

(240) 760-6970; ncilltct@mail.nih.gov

Sara K Silbert, M.D.

CONTACT

(240) 858-3666; sara.silbert@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2026
• First Posted: January 9, 2026
• Study Start (Estimated): May 11, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-04-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
• Access Criteria: Clinical data will be made available upon request and with the permission of the study PI. Genomic data are made available via dbGAP through requests to the data custodians.

Locations

US (1)