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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Lymphoblastic Leukemia; B-All
• Intervention / Treatment: Biological: CD22 CAR-transduced T cells; Drug: Cyclophosphamide; Drug: Fludarabine

Detailed 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 mortality.
• Leukemic antigen escape has led to the interest in multi-antigen targeting approaches, targeting both CD19 and CD22 to enhance the long-term effectiveness of CAR T-cells. We have previously treated patients on phase 1/2 clinical trials using a bivalent CD19/22 CAR T-cell as well as a bicistronic CD19xCD22 CAR T-cell as combinatorial strategies.
• Some of the best long-term results in the literature have been seen with co-infusion of CD19 and CD22 CAR T-cells. Three FDA-approved CD19 CAR T-cell products are available commercially, and our phase 1/2 trial of CD22 CAR T-cells has demonstrated efficacy and safety.
• The use of CD22 CAR T-cells as consolidation of CD19 CAR T-cell-induced remission offers the potential to extend the durability of remission while limiting the toxicity associated with HSCT.

Objective:

-To determine the 1-year relapse-free survival (RFS) from the time of CD22 CAR T-cell infusion.

Eligibility:

-Participants aged 3-65 years who have relapsed/refractory B-ALL with a history of demonstrated expression of CD19 and CD22 and have achieved an MRD-negative remission after receiving an FDA-approved CD19 CAR T-cell product.

Design:

• Single-arm study with 4 days lymphodepleting preparative regimen, including fludarabine and cyclophosphamide, followed by CD22 CAR T-cells administration.
• Participants will be evaluated for toxicity, antitumor effects, CAR expansion and persistence, and other biological correlatives for 2 years after cell infusion.
• The trial will accrue 16 evaluable participants. The accrual ceiling for the trial is 20 participants to account for inevaluable participant and screen failures.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: NCI Pediatric Leukemia, Lymphoma Transpl; Phone Number: (240) 760-6970; Email: ncilltct@mail.nih.gov
• Study Contact Backup: Name: Sara K Silbert, M.D.; Phone Number: (240) 858-3666; Email: sara.silbert@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: National Cancer Institute Referral Office; Phone Number: 888-624-1937; Email: ncimo_referrals@mail.nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 1; Lymphodepleting chemotherapy followed by CD22 CAR T-cells

Biological: CD22 CAR-transduced T cells; 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 500 mg/m^2/dose after fludarabine infusion on days -3 and -2.; Drug: Fludarabine; 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year RFS	RFS probability will be reported along with 95% confidence intervals.	2 years post cell infusion
1-year and 2-year OS (overall survival)	OS of participants will be assessed by Kaplan-Meier curves along with 95% confidence intervals. OS will be described for participants with HSCT and without HSCT, for descriptive purposes, along with 95% confidence intervals.	2 years post cell infusion
Short-term safety	Short-term safety of CD22 CAR T-cell infusion for participants in remission after CD19 CAR T-cell infusion will be evaluated by describing: CRS incidence and severity per ASTCT; ICANS incidence and severity per ASTCT; EC-HS incidence and severity; ICAHT incidence and severity; and incidence of grade >= 3 serious adverse events per CTCAE v.5.0.	28 days post cell infusion
Long-term safety	Long-term safety of CD22 CAR T-cell infusion for participants in remission after CD19 CAR T-cell infusion will be evaluated by describing: incidence of severe adverse events related to CD22 CAR T-cells	up to 2 years post cell infusion
RFS from the time of additional CD22 CAR T-cell infusions	RFS probability will be reported along with 95% confidence intervals.	up to 2 years post-cell infusion

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sara K Silbert, M.D., National Cancer Institute (NCI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Estimated): June 9, 2026
• Primary Completion (Estimated): January 31, 2030
• Study Completion (Estimated): January 31, 2031

Study Registration Dates

• First Submitted: January 8, 2026
• First Submitted That Met QC Criteria: January 8, 2026
• First Posted (Actual): January 9, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: May 6, 2026

More Information

Terms related to this study

• Keywords: Acute Lymphoblastic Leukemia; CD-19 expressing tumor; CD-22 Expressing Tumor; Adoptive Immunotherapy; B-All
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: 10001986; 001986-C

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No