Acute Lymphoblastic LeukemiaPhase 2NCT07328503
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 2 study testing CD22 CAR-transduced T cells, Cyclophosphamide and Fludarabine in people with Acute Lymphoblastic Leukemia and B-All, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 65 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, B-All
- What is being tested?
- CD22 CAR-transduced T cells, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Jun 2026to 31 Jan 2032
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
National Cancer Institute Referral Office, 888-624-1937, ncimo_referrals@mail.nih.gov
About this study
Official title: 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.
Read more
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.
Read the 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.
- Conditions
- Acute Lymphoblastic Leukemia, B-All
- Being tested
- CD22 CAR-transduced T cells, Cyclophosphamide, Fludarabine
- Keywords
- B-All, Acute Lymphoblastic Leukemia, CD-22 Expressing Tumor, CD-19 expressing tumor, Adoptive Immunotherapy
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD22 CAR-transduced T cellsBiological
CD22-CAR-transduced T cells on D0 after lymphodepleting preparative regimen
CyclophosphamideDrug
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.
FludarabineDrug
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).
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Lymphodepleting chemotherapy followed by CD22 CAR T-cells Receives: Biological: CD22 CAR-transduced T cells; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 1 year post cell infusion
Secondary outcomes (5)
2-year RFS
RFS probability will be reported along with 95% confidence intervals.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: up to 2 years post-cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2026
- Study start16 Jun 2026
- Primary completion31 Jan 2030 (estimated)
- Study completion31 Jan 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Sara K Silbert, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07328503
- Sponsor's protocol ID
- 10001986
- Other IDs
- 001986-C
- Status last verified
- 20 Oct 2026
- First submitted
- 8 Jan 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.