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Recurrent B Acute Lymphoblastic LeukemiaPhase 1NCT07758673

Genetically Engineered Cells (BAFFR-CAR T Cells) for the Treatment of Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Lymphoblastic Lymphoma

A Phase 1 study testing Autologous BAFFR-targeting CAR T Cells, Biospecimen Collection and Bone Marrow Aspiration in people with Recurrent B Acute Lymphoblastic Leukemia and Recurrent B Lymphoblastic Lymphoma, run by City of Hope Medical Center at 2 sites in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record

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Trial summary

This phase I trial tests the safety and side effects of B-cell activating factor receptor (BAFFR) chimeric antigen receptor (CAR) T cells and how well they work in treating patients with B-cell acute lymphoblastic leukemia (B-ALL) and B-cell lymphoblastic lymphoma that has come back after a period of improvement… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Autologous BAFFR-targeting CAR T Cells, Biospecimen Collection and Bone Marrow Aspiration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
2 sitesUnited States
Study dates
17 Apr 2027to 26 Jul 2028
Phase
Phase 1

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Documented informed consent of the participant and/or legally authorized representative
  • Agreement to allow the use of archival tissue from diagnostic tumor biopsies
  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) ≤ 2
  • Life expectancy ≥ 16 weeks
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  • Histologically confirmed B-ALL or B-cell lymphoblastic lymphoma
  • Relapsed/refractory disease. Minimal residual disease (MRD) relapse is allowed
  • Evidence of tumor expressing BAFF-R at any level either by flow or immunohistochemistry
  • Recovered to ≤ grade 1 from the acute toxic effects (except alopecia and peripheral neuropathy) of prior anti-cancer therapy
  • No known contraindications to leukapheresis, steroids or tocilizumab
  • Ineligible for or failed prior CD19-targeted immunotherapy (e.g., blinatumomab or CD19-CAR T cells)
  • For participants who had prior CD19-CAR T cell therapy:
  • At least 90-days has elapsed since participant received last CD19-CAR T cell therapy AND
  • Persistence of prior CD19-CAR T cells must be evaluated and found to be < 5% prior to leukapheresis procedure
  • Note: Participants who have undergone stem cell transplantation (at least 100 days prior to enrollment) after the last CD19-CAR T cell therapy, are considered eligible and do not need to meet the above criteria
  • Participants with central nervous system (CNS) involvement by leukemia (CNS2 and asymptomatic CNS3) may be considered eligible after discussions with the study team
  • Total serum bilirubin ≤ upper limit of normal (ULN) (unless has Gilbert's disease or related to liver involvement by leukemia, then ≤ 3.0)
  • Aspartate aminotransferase (AST) ≤ ULN, unless related to liver involvement by ALL, then ≤ 3.0
  • Alanine aminotransferase (ALT) ≤ ULN, unless related to liver involvement by ALL, then ≤ 3.0
  • Creatinine clearance of ≥ 40 mL/min per 24-hour urine test or the Cockcroft-Gault formula
  • Left ventricular ejection fraction (LVEF) ≥ 50%
  • Oxygen (O2) saturation ≥ 92% on room air
  • Seronegative for HIV quantitative polymerase chain reaction (qPCR), hepatitis C virus (HCV), and active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR])
  • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed OR
  • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. The viral load must be undetectable
  • Meets other institutional and federal requirements for infectious disease titer requirements
  • Note Infectious disease testing to be performed within 28 days prior to start of protocol therapy
  • Women of childbearing potential (WOCBP): Negative urine or serum pregnancy test
  • If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • QuantiFERON-tuberculosis (TB) Gold or equivalent
  • Results do not impact patient eligibility; however, the test must be initiated prior to enrollment
  • Agreement by females and males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
  • A complete liver evaluation (which includes ultrasound elastography, MRI of the liver and a hepatology consult) may be done if needed based on PI's recommendation

Who cannot join

  • Autologous/allogeneic stem cell transplant within 100 days at the time of enrollment
  • Immunosuppressant medications within 1 month prior to protocol enrollment
  • Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone ≤ 7.5 mg /day or equivalent) is allowed
  • Auto-immune disease or active graft-versus-host disease (GvHD) within 3 months prior to protocol enrollment requiring systemic immunosuppressant therapy
  • Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
  • Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within 2 weeks of enrollment
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  • Any abnormal liver enzyme levels (as defined by grade 1 elevation from ULN in ALT, AST, and bilirubin levels) at time of enrollment, unless they are abnormal due to liver involvement by leukemia per the treating physician's discretion
  • Subjects with a known history or prior diagnosis of uncontrolled central nervous system (CNS) disorders such as optic neuritis or other immunologic or inflammatory disease affecting the CNS, including uncontrolled seizure disorder
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
  • Known significant bleeding disorders (e.g., severe von Willebrand's disease) or hemophilia
  • History of venous occlusive disease (VOD), or GvHD
  • Subjects with a history of the following GvHD may still be included in the study:
  • Resolved grade 2 or less steroid-sensitive acute skin GvHD
  • Grade 1 gastrointestinal (GI)-GvHD developed within 100 days post prior alloHCT
  • Limited chronic GVHD
  • History of stroke or intracranial hemorrhage within 6 months of enrollment
  • History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for ≥ 2 years
  • Clinically significant uncontrolled illness
  • Active systemic uncontrolled infection
  • Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
  • Females only: Pregnant or breastfeeding
  • Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
  • Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States2 sites

  • City of Hope Medical Center

    Duarte, California, 91010

    Ibrahim Aldoss, 626-218-2405, ialdoss@coh.org

    Ibrahim Aldoss

  • City of Hope at Irvine Lennar

    Irvine, California, 92618

    Ibrahim Aldoss, 626-218-2405, ialdoss@coh.org

    Ibrahim Aldoss

Other trials in United States

About this study

Official title: A Phase 1 Study to Evaluate BAFFR-Targeting CAR T Cells for Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

This phase I trial tests the safety and side effects of B-cell activating factor receptor (BAFFR) chimeric antigen receptor (CAR) T cells and how well they work in treating patients with B-cell acute lymphoblastic leukemia (B-ALL) and B-cell lymphoblastic lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). CAR T-cell therapy, such as BAFFR-CAR T cells, is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Giving BAFFR-CAR T cells may be safe, tolerable and/or effective in treating patients with relapsed or refractory B-cell ALL and B-cell lymphoblastic lymphoma.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Assess the safety of administering autologous BAFFR-targeting CAR T cells (BAFFR[EQ]BBζ/EGFRt T cells) (also known as [aka], BAFFR-CAR T cells).

SECONDARY OBJECTIVES:

  1. Evaluate the ability of BAFFR-CAR T cells to mediate clinical response in participants with B-ALL.

II. Evaluate the level of residual disease in participants who achieve remission after BAFFR-CAR T cell treatment.

III. Evaluate the duration of B cell aplasia as a surrogate for BAFFR-CAR T cell activity.

IV. Evaluate the rate and severity of graft-versus-host disease (GVHD) in recipients of prior allogeneic hematopoietic stem cell transplantation (allogeneic hematopoietic stem cell transplantation [allo-HCT]).

  1. Evaluate progression-free survival (PFS) and overall survival (OS).

EXPLORATORY OBJECTIVES:

  1. Measure expansion and persistence of BAFFR-CAR T cells in the peripheral blood (PB), bone marrow (BM), and cerebrospinal fluid (CSF), when available, and explore the correlation with BAFFR-CAR T cell efficacy.

II. Measure BAFF-R expression on leukemic cells, as well as other disease markers, before and after BAFFR-CAR T cell treatment and explore association with response and relapse, when feasible.

III. Measure cytokine levels in PB and CSF, when available, and explore association with response.

OUTLINE:

Patients undergo leukapheresis and may receive bridging therapy per treating physician discretion. Patients then receive lymphodepletion therapy with cyclophosphamide intravenously (IV) and fludarabine IV on days -5 to -3 and BAFFR-CAR T cells IV over 10-15 minutes on day 0. Patients also undergo blood sample collection, bone marrow aspiration and biopsy, chest x-ray, and positron emission tomography (PET)/computed tomography (CT) or CT throughout the study. Additionally, patients may also undergo liver ultrasonographic elastography at screening at discretion of investigator and brain magnetic resonance imaging (MRI) or CT, CSF specimen collection, and echocardiography (ECHO) or multigated acquisition scan (MUGA) throughout the study

After completion of study treatment, patients are followed up within 18-24 hours, at least every 2 days for 14 days, at 14, 21, 28, 60, and 100 days, at 4, 6, 7, and 12 months, then yearly for up to a total of 15 years.

Being tested
Autologous BAFFR-targeting CAR T Cells, Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Bridge Therapy
Medical subject headings
Burkitt Lymphoma, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous BAFFR-targeting CAR T CellsBiological

    Also called Autologous BAFFR-CAR T Cells, Autologous BAFFR-CAR-expressing T-cells

    Given IV

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo blood and CSF specimen collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration and biopsy

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow aspiration and biopsy

  • Bridge TherapyProcedure or surgery

    Also called Holding Therapy

    Receive bridging therapy

  • Chest RadiographyProcedure or surgery

    Also called Chest X-ray

    Undergo chest x-ray

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT or PET/CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocyte Adsorptive Apheresis, Leukocytopheresis, Therapeutic Leukopheresis, White Blood Cell Reduction Apheresis

    Undergo leukapheresis

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo brain MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo PET/CT

  • Ultrasonographic ElastographyProcedure or surgery

    Also called Ultrasound Elastography

    Undergo liver ultrasonographic elastography

Study groups in NCT07758673
Study groupRoleWhat they receive
Treatment (BAFFR-CAR T cells)ExperimentalPatients undergo leukapheresis and may receive bridging therapy per treating physician discretion. Patients then receive lymphodepletion therapy with cyclophosphamide IV and fludarabine IV on days -5 to -3 and BAFFR-CAR T cells IV over 10-15 minutes on day 0. Patients also undergo blood sample collection, bone marrow aspiration and biopsy, chest x-ray, and PET/CT or CT throughout the study. Additionally, patients may also undergo liver ultrasonographic elastography at screening at discretion of investigator and brain MRI or CT, CSF specimen collection, and ECHO or MUGA throughout the study.
Receives: Biological: Autologous BAFFR-targeting CAR T Cells; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bridge Therapy; Procedure: Chest Radiography; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography Test; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Positron Emission Tomography; Procedure: Ultrasonographic Elastography

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Will be graded using Common Terminology Criteria for Adverse Events version 5.0, American Society for Transplantation and Cellular Therapy Consensus Criteria on Cytokine Release Syndrome/Neurotoxicity, graft-versus-host disease (GVHD) criteria, and Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome identification and grading. Will be summarized by organ involved, severity, time of onset, and attribution.

    Measured: Up to 28 days after chimeric antigen receptor (CAR) T cells

  2. Dose-limiting toxicity

    Will be described individually.

    Measured: From the start of CAR T infusion up to 28 days

Secondary outcomes (6)

  1. Disease response rate

    Will be defined as complete response (CR) or CR with incomplete blood count recovery or CR with partial hematological recovery. Will be evaluated using European LeukemiaNet criteria. Rates and associated 95% binomial exact confidence limits will be estimated.

    Measured: At 4 weeks

  2. Minimal residual disease negative rate

    Will be defined by malignant cells < 0.01% by flow cytometry or clonoSEQ. Rates and associated 95% binomial exact confidence limits will be estimated.

    Measured: At 4 weeks

  3. Duration of B-cell aplasia

    Will be measured by serum immunoglobulin G level. Will be summarized by descriptive statistics.

    Measured: Up to 15 years

  4. Severity of GVHD in recipients of prior allogeneic hematopoietic stem cell transplantation

    Will be defined per Keystone criteria for acute GVHD and revised National Institutes of Health consensus on grading of chronic GVHD. Competing risk method will be used to estimate.

    Measured: Within 8 weeks after T cell infusion

  5. Progression-free survival

    Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate.

    Measured: From T cell infusion to the first observation of disease relapse/progression or death from any cause, whichever occurs first, assessed up to 15 years

  6. Overall survival

    Kaplan-Meier product limit method with log-log transformation for the confidence interval will be used to estimate.

    Measured: From T cell infusion to death from any cause, assessed up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2026
  2. Study start17 Apr 2027 (estimated)
  3. Primary completion26 Jul 2028 (estimated)
  4. Study completion26 Jul 2028 (estimated)

Resources

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07758673
Sponsor's protocol ID
260193
Other IDs
NCI-2026-05498, 260193, P30CA033572
Status last verified
Aug 2026
First submitted
6 Aug 2026
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

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