Treatment using modified T-cells for relapsed or refractory B-cell cancers
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
Run by Mayo Clinic · NCT06191887 · Data updated 2026-11-12
This study is testing a new treatment that uses specially modified T-cells to see if it can help people with hard-to-treat B-cell cancers.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 27 (estimated) |
| Sponsor | Mayo Clinic Academic / other |
| Drugs / interventions | ibrutinib, acalabrutinib, zanubrutinib, CART, CAR-T, chimeric antigen receptor, chemotherapy, Radiation, prednisone, CAR T, cyclophosphamide, fludarabine |
| Locations | 1 site (Jacksonville, Florida) |
| Status | Recruiting |
| Started | March 18, 2024 |
| Main results expected | December 31, 2040 |
| Study ends | December 31, 2040 |
| Registry record updated | February 13, 2026 |
| Trial ID | NCT06191887 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Ideal candidates are adults aged 18 and older with relapsed or refractory B-cell hematologic malignancies such as chronic lymphocytic leukemia or various types of non-Hodgkin lymphoma.
✕Probably not a fit
Patients with B-cell malignancies that do not express the BAFFR protein may not benefit from this treatment.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This phase I trial evaluates the safety and effectiveness of B-cell activating factor receptor (BAFFR)-based chimeric antigen receptor T-cells in patients with relapsed or refractory B-cell hematologic malignancies. The approach involves modifying a patient's T-cells in the laboratory to enhance their ability to target and attack cancer cells. Patients will undergo lymphodepleting chemotherapy followed by infusion of the modified T-cells. The study aims to determine the optimal dose and assess the long-term effects of this treatment.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with difficult-to-treat B-cell malignancies.
How similar studies have gone: Other studies using CAR T-cell therapies have shown promising results, indicating potential for success with this novel approach.
Who can join: the full rules
Show full inclusion / exclusion criteria
Inclusion Criteria:
* 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:
* 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
Exclusion Criteria:
* 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
* 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
Where it's running
-
Mayo Clinic in Florida
Jacksonville, Florida, United States Recruiting
Study contacts
- Principal investigator: Mohamed A. Kharfan-Dabaja, M.D., M.B.A. — Mayo Clinic
Similar studies
Other studies for the same condition or treatment. Recruiting studies are listed first.
-
CD19 CAR-T cell therapy for treating relapsed B cell cancers
This study is testing a new treatment using modified immune cells to see if it can help people with relapsed B cell cancers feel better.
-
Combination treatment for chronic lymphocytic leukemia and lymphoma
This study is testing a new combination treatment with sonrotoclax and either zanubrutinib or rituximab to see if it can help patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, and mantle cell lymphoma.
-
Q702 to treat blood cancers
This Phase 1 trial will test whether the oral drug Q702 is safe, tolerable, and what dose works best for adults with certain blood cancers who have failed or are not eligible for standard treatments.
-
Natalizumab to help prevent brain-related side effects during CAR-T therapy in certain lymphoma patients
This phase 2 study tests whether natalizumab can reduce severe ICANS in adults with recurrent or refractory DLBCL or MCL receiving CAR-T therapy.
-
Genetically engineered CAR T-cells for treating certain blood cancers
This study is testing a new type of treatment using specially modified immune cells to see if they can help people with certain blood cancers that haven't responded to other treatments.
-
Donor stem cell transplant with chemotherapy and radiation for blood cancers
This study is testing if a donor stem cell transplant combined with different doses of chemotherapy and radiation can help people with blood cancers recover better.
How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.