AzTrials
AzTrials

B-Cell Non-Hodgkin LymphomaPhase 1NCT06191887

B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells With Fludarabine and Cyclophosphamide Lymphodepletion for the Treatment of Relapsed or Refractory B-cell Hematologic Malignancies

A Phase 1 study testing Autologous BAFFR-targeting CAR T Cells, Bendamustine and Biopsy in people with B-Cell Non-Hodgkin Lymphoma and Recurrent Chronic Lymphocytic Leukemia, run by Mayo Clinic at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

This phase I trial tests safety, side effects and best dose of B-cell activating factor receptor (BAFFR)-based chimeric antigen receptor T-cells, with fludarabine and cyclophosphamide lymphodepletion, for the treatment of patients with B-cell hematologic malignancies 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, Bendamustine and Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
18 Mar 2024to 31 Dec 2040
Phase
Phase 1
Are there results?
Not yet: the study is under way

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

  • PRE-REGISTRATION: Age ≥ 18 years
  • PRE-REGISTRATION: Confirmed diagnosis of 1 of the following relapsed or refractory B-cell hematologic malignancies: chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), or large B cell lymphoma (LBCL) including Richter's transformation from CLL/SLL
  • For CD19+ B cell malignancies; relapsed or refractory disease is defined by one of the following histopathology:
  • Biopsy proven SLL or flow cytometry proven CLL; relapsed or refractory disease is defined as:
  • Demonstration of progressive or stable disease by positron emission tomography/computed tomography (PET/CT) or computed tomography (CT) criteria according to the international workshop on chronic lymphocytic leukemia (iwCLL) 2018 criteria
  • Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease is defined as:
Show all 38Show fewer
  • Demonstration of progressive or stable disease by PET/CT or CT criteria as the best response to the most recent chemotherapy regimen according to the revised Lugano Response Criteria for Malignant Lymphoma
  • PRE-REGISTRATION: Disease Specific prior lines of therapies below:
  • For CLL/SLL, patients must have received ≥ two prior lines of therapy, and/or ≥ 6 months of second line prior BTK inhibition (e.g. ibrutinib or other such as acalabrutinib or zanubrutinib) and must have failed to respond to venetoclax or be intolerant. Exception: Patients in stable disease (SD) or partial response (PR) with a known ibrutinib resistance mutation (BTK or phospholipase Cγ2) may be included even if on ibrutinib therapy for less than 6 months
  • These patients may or may not have received prior antibody directed against cluster of differentiation 20 (CD20).
  • For Follicular Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
  • NOTE: Prior cluster of differentiation 19 (CD19) directed chimeric antigen receptor T-cell therapy (CART) must have a 100-day washout period.
  • For Mantle Cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20, and a BTK inhibitor.
  • NOTE: Prior CD19 directed CART must have a 100-day washout period.
  • For Marginal Zone Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
  • NOTE: Prior CD19 directed CART must have a 100-day washout period.
  • For Large B cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20. Prior exposure to CD19 directed CART will be allowed at the discretion of the Principal Investigator.
  • NOTE: Prior failed CD19 directed CART must have a 100-day washout period
  • For Richter's Transformation, patients must have received ≥two prior lines of therapy, including an antibody directed against CD20.
  • 100-day washout period starts from the date of the last prior CAR-T infusion.
  • PRE-REGISTRATION: Measurable disease
  • REGISTRATION: Positive BAFFR test
  • REGISTRATION: Measurable disease
  • REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
  • REGISTRATION: Hemoglobin ≥ 9.0 g/dL (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration
  • REGISTRATION: Absolute neutrophil count (ANC) ≥ 1500/mm^3 (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration
  • REGISTRATION: Platelet count ≥100,000/mm^3 (unless due to documented marrow involvement with disease) obtained ≤ 14 days prior to registration
  • REGISTRATION: Total bilirubin ≤ 1.5 x upper limits of normal (ULN) (Subjects with Gilbert's Syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN) obtained ≤ 14 days prior to registration
  • REGISTRATION: Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 3 x ULN (≤ 5 x ULN for patients with liver involvement) obtained ≤ 14 days prior to registration
  • REGISTRATION: Prothrombin time (PT)/international normalized ratio (INR) /activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN OR if patient is receiving anticoagulant therapy and INR or aPTT is within target range of therapy obtained ≤ 14 days prior to registration
  • Patients on a stable, maintenance regimen of anticoagulant therapy for ≥ 30 days prior to registration may have PT/INR measurements > 1.5 X ULN if, in the judgment of the investigator, the patient is suitable for the study
  • REGISTRATION: Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula obtained ≤ 14 days prior to registration
  • REGISTRATION: Negative pregnancy test done ≤ 7 days prior to registration, for persons of childbearing potential only. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
  • REGISTRATION: Provide written informed consent understand and comply with protocol-required study procedures
  • REGISTARTION: Patients must have an ejection fraction (EF) of ≥ 45%
  • REGISTRATION: Patients must have pulse ox measurements of > 92% on room air
  • REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
  • REGISTRATION: Willing to return to enrolling institution for study follow-up

Who cannot join

  • PRE-REGISTRATION: Prior solid organ transplantation
  • PRE-REGISTRATION: Unstable angina, clinically significant arrhythmia, or myocardial infarction ≤ 6 months of prior to pre-registration, or grade 3 or higher pericardial effusion at the time of pre-registration
  • PRE-REGISTRATION: Prior anti-BAFF-R therapies
  • PRE-REGISTRATION: Known contraindication to lymphodepleting (LD) chemotherapy
  • PRE-REGISTRATION: Use of systemic antitumor therapy or investigational agent ≤ 14 days, prior to pre-registration
  • PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the BAFF-R
Show all 27Show fewer
  • PRE-REGISTRATION: Autologous HCT ≤ 60 days prior to pre-registration
  • PRE-REGISTRATION: Uncontrolled intercurrent non-cardiac illness including, but not limited to:
  • Previous or concurrent malignancy
  • Ongoing or active infection
  • Psychiatric illness/social situations
  • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy * Persons of childbearing potential who are pregnant or breastfeeding
  • Life Expectancy of < 6 weeks
  • Persons requiring systemic corticosteroids (>10 mg prednisone or equivalent per day) and/or other immunosuppressive therapy. Patients are allowed to use topical corticosteroids
  • Any other conditions that would limit compliance with study requirements
  • PRE-REGISTRATION: Detectable malignant cells from cerebrospinal fluid (CSF) or magnetic resonance imaging (MRI) indicating brain metastases during screening, or a history of central nervous system (CNS) involvement by malignancy (CSF or imaging) with still active disease. Note: Patients with a history of CNS involvement resolving after treatment and without active disease will be considered eligible if other inclusion criteria are met
  • PRE-REGISTRATION: History of a seizure disorder, major cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  • PRE-REGISTRATION: Radiation therapy ≤ 14 days prior to pre-registration
  • PRE-REGISTRATION: Prior allogeneic hematopoietic stem cell transplant (HCT) in ≤ 6 months prior to pre-registration; patients with active graft versus host disease (GVHD) will not be eligible regardless of duration from prior allogeneic HCT
  • PRE-REGISTRATION: Human immunodeficiency virus (HIV) positive patients
  • PRE-REGISTRATION: Subjects with New York Health Association (NYHA) class III or greater heart failure
  • REGISTRATION: Eligible for auto-HCT based on investigator judgement
  • REGISTRATION: Presence of active bacterial, viral, or fungal infection that is uncontrolled, based on investigator judgment
  • REGISTRATION: Patients with active hepatitis B or hepatitis C infections are excluded from the study. Patients who are documented to be HIV positive or proven HIV infection from testing are ineligible for the study. Infectious disease testing (HIV-1, HIV-2, hepatitis C virus (HCV) antibody and polymerase chain reaction (PCR), hepatitis B virus (HBV) surface antigen, HBV surface antibody, HBV core antibody) performed ≤ 45 days prior to registration may be considered for subject eligibility
  • REGISTRATION: Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥ 5 years prior to registration
  • REGISTRATION: Persons of childbearing potential who are pregnant or breastfeeding
  • REGISTRATION: Life expectancy of < 6 weeks

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

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

    Clinical Trials Referral Office, 855-776-0015, mayocliniccancerstudies@mayo.edu

    Mohamed A. Kharfan-Dabaja, M.D., M.B.A.

    Recruiting

Other trials in United States

About this study

Official title: Phase 1a/1b Dose Escalation and Cohort Expansion Study of the Safety and Efficacy of B-Cell Activating Factor Receptor (BAFFR)-Based Chimeric Antigen Receptor T-Cells (MC10029) in Subjects With Relapsed or Refractory BAFFR-Expressing B-Cell Hematologic Malignancies

This phase I trial tests safety, side effects and best dose of B-cell activating factor receptor (BAFFR)-based chimeric antigen receptor T-cells, with fludarabine and cyclophosphamide lymphodepletion, for the treatment of patients with B-cell hematologic malignancies that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). BAFFR-based chimeric antigen receptor 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 chimeric antigen receptor (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 chemotherapy, such as fludarabine and cyclophosphamide, helps ill cancer cells in the body and helps prepare the body to receive the BAFFR based chimeric antigen receptor T-cells. Giving BAFFR based chimeric antigen receptor T-cells with fludarabine and cyclophosphamide for lymphodepletion may work better for the treatment of patients with relapsed or refractory B-cell hematologic malignancies.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To assess the safety and tolerability of (MC10029) autologous BAFFR-targeting chimeric antigen receptor (CAR) T cells following lymphodepleting (LD) therapy in subjects with relapsed or refractory BAFFR expressing B-cell hematologic malignancies.

II. To determine the recommended dose for phase 1b (dose expansion) and recommend phase 2 dose.

SECONDARY OBJECTIVES:

  1. To assess the efficacy and antitumor activity of MC10029 in subjects with relapsed or refractory BAFFR-expressing B-cell hematologic malignancies.

II. To determine long-term toxicities in MC10029 recipients. III. To determine feasibility of manufacturing success rate of MC10029.

CORRELATIVE RESEARCH OBJECTIVES:

  1. To evaluate the pharmacokinetics of MC10029 in peripheral blood samples. II. To study the relationship between BAFFR expression and clinical activity of MC10029.

OUTLINE:

Patients undergo leukapheresis. Patients then receive cyclophosphamide intravenously (IV), over 60 minutes and fludarabine IV over 30 minutes on day -5 to -3 or bendamustine IV over 10 minutes on days -4 and -3. Patients receive BAFFR based chimeric antigen receptor T-cells IV on day 0. Patients undergo echocardiography and magnetic resonance imaging (MRI) at screening, computed tomography (CT) scan, positron emission tomography (PET) scan, bone marrow biopsy/aspirate and blood sample collection throughout the study and tumor biopsy at progression.

After completion of study treatment, patients followed up at day 1, 2, 3, 4, 8, 11, 14, 21, 28, 60, 90, 180, 270, 365, 545 and 730 and then periodically for up to 15 years.

Being tested
Autologous BAFFR-targeting CAR T Cells, Bendamustine, Biopsy, Biospecimen Collection, Bone Marrow Aspiration and Biopsy
Medical subject headings
Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, B-Cell, Marginal Zone

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

  • BendamustineDrug

    Also called SDX-105

    Given IV

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow Aspiration and BiopsyProcedure or surgery

    Undergo bone marrow biopsy/aspirate

  • Computed TomographyProcedure or surgery

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

    Undergo CT scan

  • 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

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo echocardiography

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo MRI

  • Positron Emission TomographyProcedure or surgery

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

    Undergo PET scan

Study groups in NCT06191887
Study groupRoleWhat they receive
Treatment (BARRF based chimeric antigen receptor T-cells)ExperimentalPatients undergo leukapheresis. Patients then receive cyclophosphamide IV, over 60 minutes and fludarabine IV over 30 minutes on day -5 to -3 or bendamustine IV over 10 minutes on days -4 and -3. Patients receive BAFFR based chimeric antigen receptor T-cells IV on day 0. Patients undergo echocardiography and MRI at screening, CT scan, PET scan, bone marrow biopsy/aspirate and blood sample collection throughout the study and tumor biopsy at progression.
Receives: Biological: Autologous BAFFR-targeting CAR T Cells; Drug: Bendamustine; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Positron Emission Tomography

What is being measured

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

  1. Incidence of dose-limiting toxicities (DLT)

    DLTs are defined per the protocol and assessed by the number of DLTs that occur during the DLT evaluation period and persist beyond the specified duration (relative to the time of onset, defined as within 28 days).

    Measured: Up to 28 days after MC10029 (autologous B-cell activating factor receptor [BAFFR]-targeting chimeric antigen receptor [CAR] T cells product) infusion

  2. Incidence and severity of treatment emergent adverse events

    Defined as adverse events (AEs) that occur or worsen in severity on or after MC10029 product infusion.

    Measured: Up to 15 years

Secondary outcomes (6)

  1. Overall response rate

    Will be estimated by the number of patients with an objective status of complete response (CR) or partial response (PR) by the positron emission tomography-computed tomography (PET-CT) based response criteria . Will be assessed according to Lugano criteria for lymphomas (follicular lymphoma [FL], mantle cell lymphoma [MCL], marginal zone lymphoma [MZL], large b-cell lymphoma [LBCL]) and International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria for chronic lymphocytic leukemia (CLL).

    Measured: Up to 15 years

  2. Complete response rate

    Will be assessed according to Lugano criteria for lymphomas (FL, MCL, MZL, LBCL) and iwCLL 2018 criteria for CLL.

    Measured: Up to 15 years

  3. Duration of response

    Defined as the time from onset of response to progression or death due to any reason, whichever occurs earlier.

    Measured: Up to 15 years

  4. Progression free survival

    Defined as the time from initiation of treatment to the occurrence of disease progression or death.

    Measured: Up to 15 years

  5. Overall survival

    Defined as the time from treatment to death, regardless of disease recurrence.

    Measured: Up to 15 years

  6. Number of conforming versus nonconforming products

    Will be noted and reported. A conforming cell product product must have met all release criteria for infusion. No patient will receive a non-conforming product under this protocol, thus this endpoint will be evaluated by the Quality Assurance/Quality Control team.

    Measured: 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 posted5 Jan 2024
  2. Study start18 Mar 2024
  3. Primary completion31 Dec 2040 (estimated)
  4. Study completion31 Dec 2040 (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
27 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06191887
Sponsor's protocol ID
MC230807
Other IDs
NCI-2023-10077, 23-004166, MC230807
Status last verified
Feb 2026
First submitted
20 Dec 2023
Last updated
13 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous BAFFR-targeting CAR T Cells, Bendamustine and Biopsy in people with B-Cell Non-Hodgkin Lymphoma and Recurrent Chronic Lymphocytic Leukemia, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities (DLT) (time frame: Up to 28 days after MC10029 (autologous B-cell activating factor receptor [BAFFR]-targeting chimeric antigen receptor [CAR] T cells product) infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06191887.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Feb 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in