Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)

NCT07572136 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10001555001555-C
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

Background: B-cell acute lymphoblastic leukemia (B-ALL) is a type of blood cancer. Some people with B-ALL have a gene mutation that makes the disease hard to treat. The mutation causes cancer cells to make too much of a protein called thymic stromal lymphopoietin receptor (TSLPR). Chimeric antigen receptor (CAR) T cell therapy is a treatment that takes immune cells (T cells) from a person s body and modifies them to attack specific proteins. Researchers want to test whether TSLPR-CART cells can be given safely to adults with forms of B-cell leukemia, and to learn whether the treatment may help fight these cancers. Objective: To test TSLPR-CART in people with B-ALL. Eligibility: People aged 18 years and older with B-ALL that did not respond or returned after treatment. They must have TSLPR on their B-ALL. Design: Participants will be screened. They will have imaging scans and tests of their heart function. Samples will be taken from their bone marrow. They will have a lumbar puncture: A needle will be inserted into their back to collect a sample of the fluid around the spinal cord. Participants will undergo leukapheresis: Blood will be taken from their body through a tube. 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 tube. The T cells will be used to create TSLPR-CART. Participants will take chemotherapy over 5 days to prepare their body for the therapy; then they will receive the modified cells through a tube inserted into a vein. Staying in the hospital during part of the treatment is expected and participants will be monitored locally to evaluate for side effects. Approximately 1 month after receiving TSLPR-CART, participants will undergo evaluations to see how the TSLPR-CART impacted their leukemia. Participants will have follow-up visits for 2 years after TSLPR-CART either at NIH or at home....

Conditions

B-All; Acute Lymphoblastic Leukemia

Keywords

Adoptive Immunotherapy; CRLF2-R/TSLPR Expressing Tumor; Acute Lymphoblastic Leukemia; B-All

Outcome Measures

Primary Outcomes (1)

• To assess the safety of administering escalating doses of TSLPR-CART containing a tEGFR suicide switch to determine an MTD

  Safety analyses will consist of tabulations of grades of toxicity by type of toxicity

  28 days post cell infusion

Secondary Outcomes (2)

• Efficacy of TSLPR-CART

  2 years post cell infusion

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

  2 years post cell infusion

Study Arms (2)

1

EXPERIMENTAL

TSLPR-CART at escalating doses

Biological: TSLPR-CART; Drug: Cyclophosphamide; Drug: Fludarabine

2

EXPERIMENTAL

TSLPR-CART at MTD or highest dose administered

Biological: TSLPR-CART; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

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; 2

TSLPR-CART BIOLOGICAL

TSLPR CAR transduced T cells on D0 after lymphodepleting preparative regimen

1; 2

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; 2

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documentation of pathologic confirmation of a diagnosis of B-Cell acute lymphoblastic leukemia (ALL).
• TSLPR+ expression must be detected on \>=80% of the malignant cells by NSR device. Note: TSLPR+ expression does not need to be repeated by NSR device if there is a documentation of TSLPR surface expression by flow cytometry from a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory.
• Participants must have a disease that is relapsed or refractory after initial systemic therapy and at least one salvage treatment, and must either be ineligible for, cannot access in a timely manner, or declined alternative curative options (including commercial CAR Tcell constructs\*, and/or have relapsed after allogeneic HSCT).
• \*Individuals that are CD19 positive will be considered for this study, However, these individuals should be ineligible for, unable to obtain in a timely manner, cannot access, unwilling to undergo, or have failed prior FDA approved CD19 CAR constructs.
• Participants must have measurable or evaluable disease at the screening, defined by any evidence of MRD or positron emission tomography (PET)-avid extramedullary disease
• Age \>= 18 years
• Clinical performance status: Karnofsky \>= 50%. Participants who are unable to walk because of paralysis, but who are upright in a wheelchair will be considered ambulatory for the purpose of calculating the performance score.
• Participants must have adequate organ and marrow function as defined below:
• Leukocytes \>= 750/mcL\*
• Platelets \>= 50,000/mcL\*
• Total bilirubin \<= 2 x upper limit of normal (ULN) (except in the case of participants with documented Gilbert s disease \> 3 X ULN)
• Aspartate Aminotransferase (AST)/Alanine Aminotransferase (ALT) \<= 5 X institutional ULN
• Creatinine \< 1.5X ULN OR Creatinine clearance \>= 60 mL/min/1.73m\^2 for participants with creatinine levels above max listed above
• A participant will not be excluded because of pancytopenia \>=Grade 3 if it is due to underlying bone marrow involvement by leukemia
• Cardiac function: left ventricular ejection fraction (LVEF) \>=45% or fractional shortening \>= 28%, and no clinically significant electrocardiogram (EKG) findings

You may not qualify if:

• <!-- -->
• Recurrent or refractory leukemia limited to isolated testicular or isolated CNS disease
• Hyperleukocytosis (\>=50,000 blasts/mcL)
• Positive serum or urine beta-human chorionic gonadotropin (beta-HCG) pregnancy test performed in WOCBP at screening.
• Washout criteria (time prior to apheresis or prior to start of LD if apheresis is not done on this protocol):
• ====
• Therapy: Systemic chemotherapy, antineoplastic investigational agents, or antibody-based therapies, any investigational therapy
• Washout\*: \>= 2 weeks
• Exceptions: 6 weeks for clofarabine or nitrosoureas No washout for prior intrathecal chemotherapy, steroid therapy, hydroxyurea (no dose increases within prior 2 weeks) or ALL maintenance type chemotherapy (vincristine, 6- mercaptopurine, oral methotrexate, or a tyrosine kinase for participants with Ph+ or Ph-like ALL) provided there is recovery from any acute toxic effects.
• ====
• Therapy: Radiation therapy
• Washout\*: \>= 3 weeks
• Exceptions: No time restriction with radiation therapy if the volume of bone marrow treated is less than 10% and the participant has measurable/evaluable disease outside the radiation window.
• ====
• Therapy: History of allogeneic HSCT

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

• John W Glod, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

NCI Ped LeukemiaLymph Cell Tx Tm

CONTACT

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

John W Glod, M.D.

CONTACT

(240) 760-6194; john.glod@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: May 7, 2026
• Study Start (Estimated): August 5, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2032
• Last Updated: July 31, 2026

Record last verified: 2026-07-20

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)