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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

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Conditions

B-Cell Non-Hodgkin LymphomaRecurrent Chronic Lymphocytic LeukemiaRecurrent Diffuse Large B-Cell LymphomaRecurrent Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaRecurrent Transformed Chronic Lymphocytic LeukemiaRefractory Chronic Lymphocytic LeukemiaRefractory Diffuse Large B-Cell LymphomaRefractory Follicular LymphomaRefractory Mantle Cell LymphomaRefractory Marginal Zone LymphomaRefractory Small Lymphocytic LymphomaRefractory Transformed Chronic Lymphocytic Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2024-03-18
Study Completion:2040-12-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT06191887

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * PRE-REGISTRATION: Age ≥ 18 years
  2. * 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
  3. * For CD19+ B cell malignancies; relapsed or refractory disease is defined by one of the following histopathology:
  4. * Biopsy proven SLL or flow cytometry proven CLL; relapsed or refractory disease is defined as:
  5. * 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
  6. * Biopsy proven B-cell non-Hodgkin lymphoma (NHL) of any histopathology (including Richter Transformation of CLL); relapsed or refractory disease is defined as:
  7. * 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
  8. * PRE-REGISTRATION: Disease Specific prior lines of therapies below:
  9. * 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
  10. * These patients may or may not have received prior antibody directed against cluster of differentiation 20 (CD20).
  11. * For Follicular Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
  12. * NOTE: Prior cluster of differentiation 19 (CD19) directed chimeric antigen receptor T-cell therapy (CART) must have a 100-day washout period.
  13. * For Mantle Cell Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20, and a BTK inhibitor.
  14. * NOTE: Prior CD19 directed CART must have a 100-day washout period.
  15. * For Marginal Zone Lymphoma, patients must have received ≥ two prior lines of therapy, including an antibody directed against CD20.
  16. * NOTE: Prior CD19 directed CART must have a 100-day washout period.
  17. * 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.
  18. * NOTE: Prior failed CD19 directed CART must have a 100-day washout period
  19. * For Richter's Transformation, patients must have received ≥two prior lines of therapy, including an antibody directed against CD20.
  20. * 100-day washout period starts from the date of the last prior CAR-T infusion.
  21. * PRE-REGISTRATION: Measurable disease
  22. * REGISTRATION: Positive BAFFR test
  23. * REGISTRATION: Measurable disease
  24. * REGISTRATION: Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
  25. * REGISTRATION: Hemoglobin ≥ 9.0 g/dL (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration
  26. * REGISTRATION: Absolute neutrophil count (ANC) ≥ 1500/mm\^3 (unless due to documented marrow involvement with disease) obtained ≤14 days prior to registration
  27. * REGISTRATION: Platelet count ≥100,000/mm\^3 (unless due to documented marrow involvement with disease) obtained ≤ 14 days prior to registration
  28. * 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
  29. * 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
  30. * 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
  31. * 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
  32. * REGISTRATION: Calculated creatinine clearance ≥45 ml/min using the Cockcroft-Gault formula obtained ≤ 14 days prior to registration
  33. * 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
  34. * REGISTRATION: Provide written informed consent understand and comply with protocol-required study procedures
  35. * REGISTARTION: Patients must have an ejection fraction (EF) of ≥ 45%
  36. * REGISTRATION: Patients must have pulse ox measurements of \> 92% on room air
  37. * REGISTRATION: Willingness to provide mandatory blood specimens for correlative research
  38. * REGISTRATION: Willing to return to enrolling institution for study follow-up
  1. * PRE-REGISTRATION: Prior solid organ transplantation
  2. * 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
  3. * PRE-REGISTRATION: Prior anti-BAFF-R therapies
  4. * PRE-REGISTRATION: Known contraindication to lymphodepleting (LD) chemotherapy
  5. * PRE-REGISTRATION: Use of systemic antitumor therapy or investigational agent ≤ 14 days, prior to pre-registration
  6. * PRE-REGISTRATION: Receiving any other investigational agent which would be considered as a treatment for the BAFF-R
  7. * PRE-REGISTRATION: Autologous HCT ≤ 60 days prior to pre-registration
  8. * PRE-REGISTRATION: Uncontrolled intercurrent non-cardiac illness including, but not limited to:
  9. * Previous or concurrent malignancy
  10. * Ongoing or active infection
  11. * Psychiatric illness/social situations
  12. * 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
  13. * Life Expectancy of \< 6 weeks
  14. * Persons requiring systemic corticosteroids (\>10 mg prednisone or equivalent per day) and/or other immunosuppressive therapy. Patients are allowed to use topical corticosteroids
  15. * Any other conditions that would limit compliance with study requirements
  16. * 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
  17. * PRE-REGISTRATION: History of a seizure disorder, major cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement
  18. * PRE-REGISTRATION: Radiation therapy ≤ 14 days prior to pre-registration
  19. * 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
  20. * PRE-REGISTRATION: Human immunodeficiency virus (HIV) positive patients
  21. * PRE-REGISTRATION: Subjects with New York Health Association (NYHA) class III or greater heart failure
  22. * REGISTRATION: Eligible for auto-HCT based on investigator judgement
  23. * REGISTRATION: Presence of active bacterial, viral, or fungal infection that is uncontrolled, based on investigator judgment
  24. * 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
  25. * 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
  26. * REGISTRATION: Persons of childbearing potential who are pregnant or breastfeeding
  27. * REGISTRATION: Life expectancy of \< 6 weeks

Contacts and Locations

Principal Investigator

Mohamed A. Kharfan-Dabaja, M.D., M.B.A.
PRINCIPAL_INVESTIGATOR
Mayo Clinic

Study Locations (Sites)

Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
United States

Collaborators and Investigators

Sponsor: Mayo Clinic

  • Mohamed A. Kharfan-Dabaja, M.D., M.B.A., PRINCIPAL_INVESTIGATOR, Mayo Clinic

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-03-18
Study Completion Date2040-12-31

Study Record Updates

Study Start Date2024-03-18
Study Completion Date2040-12-31

Terms related to this study

Additional Relevant MeSH Terms

  • B-Cell Non-Hodgkin Lymphoma
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Diffuse Large B-Cell Lymphoma
  • Recurrent Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Recurrent Small Lymphocytic Lymphoma
  • Recurrent Transformed Chronic Lymphocytic Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Diffuse Large B-Cell Lymphoma
  • Refractory Follicular Lymphoma
  • Refractory Mantle Cell Lymphoma
  • Refractory Marginal Zone Lymphoma
  • Refractory Small Lymphocytic Lymphoma
  • Refractory Transformed Chronic Lymphocytic Leukemia