Genetically Engineered Cells (Anti-CD19/CD20/CD22 CAR T-cells) for the Treatment of Relapsed or Refractory Lymphoid Malignancies
Phase I Clinical Trial of Anti-CD19/20/22 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Lymphoid Malignancies (Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, Chronic Lymphocytic Leukemia, B-Prolymphocytic Leukemia)
3 other identifiers
interventional
54
1 country
2
Brief Summary
This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen receptor (CAR) T-cells following a short course of chemotherapy with cyclophosphamide and fludarabine in treating patients with lymphoid cancers (malignancies) that have come back (recurrent) or do not respond to treatment (refractory). Lymphoid malignancies eligible for this trial are: non-Hodgkin lymphoma (NHL), acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), and B-prolymphocytic leukemia (B-PLL). T-cells (a type of white blood cell) form part of the body's immune system. CAR-T is a type of cell therapy that is used with gene-based therapies. CAR T-cells are made by taking a patient's own T-cells and genetically modifying them with a virus so that they are recognized by a group of proteins called CD19/CD20/CD22 which are found on the surface of cancer cells. Anti-CD19/CD20/CD22 CAR T-cells can recognize CD19/CD20/CD22, bind to the cancer cells and kill them. Giving combination chemotherapy helps prepare the body before CAR T-cell therapy. Giving CAR-T after cyclophosphamide and fludarabine may kill more tumor cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jun 2022
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 16, 2022
CompletedFirst Posted
Study publicly available on registry
June 14, 2022
CompletedStudy Start
First participant enrolled
June 30, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 30, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
July 31, 2026
ExpectedMay 16, 2025
May 1, 2025
3.8 years
May 16, 2022
May 13, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Recommended phase II dose of anti-CD19/CD20/CD22 CAR-T cells for each study group (Cohort A, Cohort B, and Cohort C)
Up to 30 days after CAR T-cell infusion
Secondary Outcomes (5)
Incidence of adverse events
Up to 12 months after completion of study treatment
Overall response rate
Up to 15 years
Complete response rate
Up to 15 years
Overall survival
Up to 15 years
Progression-free survival
From entry onto study until lymphoma progression or death from any cause, assessed up to 15 years
Other Outcomes (3)
Correlation between cytokine serum concentrations and disease response
Up to 15 years
Presence of measurable CAR-T cells
Up to 12 months
Correlation between CD19/20/22 expression on disease response
Up to 15 years
Study Arms (3)
Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells)
EXPERIMENTALLYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells)
EXPERIMENTALLYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells)
EXPERIMENTALLYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV on days -6 and -5 and fludarabine IV on days -6 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
Interventions
Undergo MUGA scan
Given IV
Given IV
Given IV
Undergo echocardiography
Undergo tissue biopsy
Undergo apheresis
Undergo bone marrow aspiration and biopsy
Undergo blood sample collection
Eligibility Criteria
You may qualify if:
- Adult subjects with relapsed or refractory non-Hodgkin lymphoma with lesions =\< 5 cm, indolent lymphomas, chronic lymphocytic leukemia without Richter's transformation, or B-prolymphocytic leukemia (Cohort A)
- OR adult subjects with lymphoid blast crisis, acute lymphoblastic leukemia, chronic lymphocytic leukemia with Richter's transformation, non-Hodgkin lymphoma with lesions \> 5 cm and/or lymphoblastic lymphoma, or non-Hodgkin lymphoma with circulating lymphoma cells, B-Prolymphocytic leukemia with lesions \> 5 cm (not including splenomegaly (Cohort B).
- OR Pediatric subjects with Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma
- Subjects must have been treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve complete remission with the last regimen. B-PLL is defined as having greater than 55% prolymphocytes in the peripheral blood
- Subjects with relapsed/refractory CLL after at least 2 prior lines of appropriate therapy and must have previously received an approved BTK inhibitor and venetoclax
- Subjects with refractory high-grade B-cell lymphoma who relapse within 12 months of autologous stem cell transplant
- Subjects with relapsed/refractory B-prolymphocytic leukemia who received at least 1- 2 prior lines of appropriate therapy and who have failed or are ineligible for allogeneic stem cell transplant
- Subjects with relapsed/refractory acute B-lymphoblastic leukemia who received at least 2 prior lines of appropriate therapy or who have failed or are ineligible for allogeneic stem cell transplant.
- The patient's lymphoid malignancy must be positive for at least one target antigen (CD19 and/or CD20 and/or CD22), either by immunohistochemistry or flow cytometry analysis on the last biopsy available or peripheral blood for circulating disease.
- Patients who received blinatumomab or inotuzumab are eligible.
- Patients who received prior CAR T-cells are eligible, (commercial CD 19 CAR-T cells or dual CAR-T cells), if it has been at least 30 days since previous CAR T cell therapy and \<5% of circulating levels of CD3+ cells express the prior CAR by flow cytometry.
- Age \>= 2 years
- Eastern Cooperative Oncology Group (ECOG) performance status =\< 2. For patients \< 16 years, Performance score Lansky \>= 50
- Total bilirubin =\< 1.5 times the institutional upper limit of normal for age
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) =\< 3 X institutional upper limit of normal for age
- +12 more criteria
You may not qualify if:
- Autologous transplant within 6 weeks of planned CAR-T cell infusion
- Allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of planned CAR-T cell infusion and patients must be off immunosuppressive agents. Patients with live vaccines given 28 days prior to lymphodepletion (LD) chemotherapy will be excluded
- Active graft versus host disease
- Active central nervous system or meningeal involvement by lymphoma or leukemia. Subjects with untreated brain metastases/central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by CSF evaluation and contrast-enhanced magnetic resonance imaging (MRI) imaging for at least 90 days prior to registration
- Active malignancy, other than non-melanoma skin cancer or carcinoma in situ (e.g.cervix, bladder, breast). Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial (e.g.
- Low Gleason score prostate Cancer)
- A minimum of 28 days must have elapsed between prior treatment with investigational agent(s) and the day of lymphocyte collection
- Human immunodeficiency virus (HIV)-seropositive patients are allowable, however must be on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment to be eligible for this trial
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of childbearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study
- Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
- Patients with a positive hepatitis B core antibody or surface antigen are at high risk for hepatitis B virus (HBV) reaction and will require entecavir/tenofivir prophylaxis or serial hepatitis B (Hep B) PCR monitoring at the direction of an infectious disease specialist. Duration of prophylaxis to correspond with detection of Anti-CD19/20/22 CAR T cells/viral vector copies in serum or continued evidence of B-cell aplasia such as reduced intravenous immunoglobulin therapy (IVIG) levels. No antiviral prophylaxis is indicated with hepatitis C positivity with negative PCR
- Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease
- History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months
- Live vaccines given in 28 days prior to lymphodepleting chemotherapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Sumithira Vasulead
- National Cancer Institute (NCI)collaborator
Study Sites (2)
Nationwide Children's Hospital
Columbus, Ohio, 43203, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sumithira Vasu, MD
Ohio State University Comprehensive Cancer Center
Central Study Contacts
The Ohio State University Comprehensive Cancer Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 16, 2022
First Posted
June 14, 2022
Study Start
June 30, 2022
Primary Completion
April 30, 2026
Study Completion (Estimated)
July 31, 2026
Last Updated
May 16, 2025
Record last verified: 2025-05
Data Sharing
- IPD Sharing
- Will not share