Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy for Leukemias
Phase I/II Trial of Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy for B-cell Leukemias
2 other identifiers
interventional
132
1 country
1
Brief Summary
Background: Chronic lymphocytic leukemia (CLL),small lymphocytic lymphoma (SLL) and B-cell acute lymphoblastic leukemia or lymphoma (ALL) are blood cancers that affect certain white blood cells. Advanced forms of these diseases are difficult to treat. CD19 is a protein often found on the surfaces of these cancer cells. Researchers can modify a person's own immune cells (T cells) to target CD19. When these modified T cells are returned to the body-a treatment called anti-CD19 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells. Objective: To test anti-CD19 CAR T cell therapy in people with CLL or SLL and ALL. Eligibility: People aged 18 years and older with CLL or SLL and ALL that has not been controlled with standard drugs. Design: Participants will be screened. They will have imaging scans and tests of their heart function. If a sample of tissue from their tumor is not available, a new one may be taken; the sample will be tested for CD19. Participants will receive a drug to reduce the leukemia cells in their blood. Then they will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be gene edited to make them attack cells with CD19. Participants will take drugs to prepare them for treatment for 3 days. These drugs will start 5 days before the treatment. Then their own modified CAR T cells will be returned to their bloodstream. Participants will stay in the hospital for at least 9 days after the treatment. Follow-up visits will continue for 5 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Sep 2024
Longer than P75 for phase_1
1 active site
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
April 12, 2024
CompletedFirst Posted
Study publicly available on registry
April 15, 2024
CompletedStudy Start
First participant enrolled
September 3, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2030
March 2, 2026
February 26, 2026
4.8 years
April 12, 2024
February 27, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Phase II: Determine the overall response rate (ORR) of T cells expressing an anti-CD19 CAR with a fully-human single chain variable fragment (scFv) to participants with advanced CLL/SLL or ALL.
Overall Response Rate will be evaluated using published criteria; these will be reported along with a 95% confidence interval
From time of the pre-leukapheresis rituximab through 5 years after CAR T infusion.
Phase I: Determine the safety of administering T-cells expressing a fully-human anti-CD19 CAR to participants with advanced CLL/ SLL orALL.
Adverse Events (AE) by type, grade, and frequency
From time of the pre-leukapheresis rituximab through 5 years after CAR T infusion.
Secondary Outcomes (5)
Phase II: Determine the proportion of grade 3-4, and 5 adverse events at the Optimal Dose
up to 5 years
Phase I+II: Determine the ORR for re treatment with rituximab, chemotherapy and CAR T cells in eligible patients
up to 5 years
Phase I+II: Assess duration of responses
up to 5 years
Phase I+II: Assess complete response rate
up to 5 years
Phase I: Assess overall response rate
up to 5 years
Study Arms (4)
1/Rituximab, conditioning chemotherapy plus CAR T-cells- Dose escalation in participants with CLL/SL
EXPERIMENTALEscalating dose of anti-CD19 CAR T- cells/kg + rituximab and conditioning chemotherapy in participants with CLL/SLL
2/Rituximab, conditioning chemotherapy plus CAR T-cells- Dose expansion in participants with CLL/SLL
EXPERIMENTALMTD dose or Optimal dose of Anti-CD19 CAR T- cells/kg + rituximab and conditioning chemotherapy in participants with CLL/SLL
3/Rituximab, conditioning chemotherapy plus CAR T-cells- Dose escalation in participants with ALL
EXPERIMENTALEscalating dose of anti-CD19 CAR T- cells/kg + rituximab and conditioning chemotherapy in participants with ALL
4/Rituximab, conditioning chemotherapy plus CAR T-cells- Dose expansion in participants with ALL
EXPERIMENTALMTD dose or Optimal dose of Anti-CD19 CAR T- cells/kg + rituximab and conditioning chemotherapy in participants with ALL
Interventions
1.0x10\^6 CAR+T-cells - 12x10\^6 CAR+ T cells/kg (weight based dosing per cohort) infused on day 0
500 mg/m\^2 IV infusion over 30 minutes on days -5, -4 and -3
30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4,and -3
500 mg/m\^2 IV infusion over 30 minutes on day -5; 375 mg/m\^2 IV infusion over 30 minutes on days 2-9 prior to apheresis
Eligibility Criteria
You may qualify if:
- Malignancy criteria
- Histologically confirmed participants with either CLL or SLL or B-cell acute lymphoblastic leukemia or lymphoma (ALL) via immunohistochemical or flow cytometry methods will be eligible. Participants with evidence of Richter s transformation of CLL/SLL are also eligible. Participants with Richter s transformation must have current or prior evidence of CLL, confirmed by review of a current or prior histological sample by NIH pathologists or confirmed by flow cytometry performed at the NIH.
- Demonstration of CD19 expression on CLL/SLL or ALL, as assessed by the NCI Laboratory of Pathology or NIH Department of Laboratory Medicine Hematopathology section. For participants with pathologically confirmed Richter s transformation, the transformed cells must also have CD19 expression.
- CD19 expression must be uniform meaning no populations of clearly CD19-negative CLL/SLL, Richter s or ALL cells are observed.
- CD20 must be detected on \>= 20% of malignant cells by flow cytometry or immunohistochemistry.
- The last dosage of systemic therapy (including corticosteroids) must be at least 14 days prior to the first dose of rituximab, with the exceptions of BTK inhibitors (BTKi) for CLL/SLL and tyrosine kinase inhibitors (TKI) for ALL. Participants who were receiving a BTKi for CLL/SLL or a TKI for ALL for at least 14 days prior to protocol enrollment can continue these agents during part of the time the participants are enrolled on this clinical trial.
- For participants who have received antibodies targeting CD19, at least sixty days must elapse between therapy with antibodies targeting CD19 and CAR T-cell infusion.
- Participants with CLL/SLL must have received at least two prior treatment regimens, at least one of which must have contained a Bruton s tyrosine kinase (BTK) inhibitor. Participants who took a BTK inhibitor but stopped due to intolerance are potentially eligible. Participants with relapsed or refractory CLL/SLL after alloHSCT are eligible.
- Participants with refractory ALL that failed induction or participants with relapsed ALL after a standard induction regimen or after any later line of therapy are eligibleParticipants with relapsed or refractory ALL after alloHSCT are eligible.
- All participants must have measurable malignancy as defined by at least one of the criteria below.
- Presence of CLL,SLL, or ALL masses that are measurable (minimum 1.5 cm in largest diameter) by CT scan or PET/CT is required unless bone marrow or blood involvement with malignancy is detected.
- For CLL/SLL or ALL with only bone marrow and/or blood involvement, no mass is necessary, but if a mass is not present, bone marrow and/or blood malignancy must be detectable by flow cytometry. Any level of CLL/SLL or ALL detectable by flow cytometry is sufficient.
- Age \>= 18 years.
- Performance status (ECOG) 0-1.
- Participants must have adequate organ and marrow function as defined below:
- +19 more criteria
You may not qualify if:
- Participants who are receiving any other investigational agents.
- Participants who have had prior CAR T-cell therapy.
- Participants who have had a live-attenuated or viral vector-based vaccine in the last 60 days prior to pre-leukapheresis rituximab. Participants who plan to receive a live attenuated or viral vector-based vaccine within the first 100 days after CAR T-cell infusion.
- Participants that require urgent therapy due to tumor mass effects or spinal cord compression.
- Current/active HIV infection, as measured by seropositivity for HIV antibody.
- Participants with second malignancies in addition to their CLL or ALL are not eligible if the second malignancy has required treatment with surgery, radiation or chemotherapy, or other therapies within the past 2 years or is not in complete remission. Exceptions are that, in the last 2 years, participants may have had successful resection of non-metastatic basal cell or squamous cell carcinoma of the skin, and participants may have received hormonal therapy for fully resected breast cancer.
- Positive beta Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in women of childbearing potential (WOCBP) performed at screening.
- Active uncontrolled systemic infections (defined as infections causing fevers within 48 hours of the date of planned protocol rituximab or chemotherapy start and infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours at the time of protocol rituximab or chemotherapy start). There must be objective evidence of infection, including, but not limited to, a positive blood, urine or sputum culture, positive nasal swab or blood test for viral infection, or the appearance of infiltrates on imaging of the lung.
- Active coagulation disorders, major uncontrolled medical illnesses of the cardiovascular, respiratory, endocrine, renal, gastrointestinal, genitourinary or immune system, history of myocardial infarction, history of ventricular tachycardia or ventricular fibrillation, active cardiac arrhythmias with the exception of atrial fibrillation with baseline heart rates less than or equal to 90 beats per minute, (Use of medications to control heart rate is allowed.), active obstructive or restrictive pulmonary disease, or active autoimmune diseases such as rheumatoid arthritis. These include uncontrolled intercurrent illness manifesting as electrolyte derangements or as assessed by chemistries.
- Significant neurologic disorders, including a history of a seizure disorder as an adult, that are not completely and permanently resolved and not requiring current treatment.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease) that has not been cured by a prior allogeneic stem cell transplant.
- For participants that have not had prior allogeneic stem cell transplant: Systemic corticosteroid steroid therapy of any dose greater than 5 mg/day or more of prednisone or equivalent is not allowed within 14 days prior to the first dose of rituximab. Corticosteroid creams, ointments, and eye drops are allowed.
- For participants that have had prior allogeneic stem cell transplant: Receiving any systemic immunosuppressive drugs including corticosteroids at doses of greater than 5 mg/day prednisone or equivalent within 28 days prior to Rituximab. Topical corticosteroid preparations applied to the skin such as solutions, creams, and ointments are allowed. Inhaled corticosteroids are allowed, and corticosteroid eye drops are allowed.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study, including hypersensitivity to aminoglycoside antibiotics, which may be used in the cell culture media.
- Participants with CNS3 disease, neurologic signs of CNS disease, radiologically detected active CNS lymphoma or meningeal involvement.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
James N Kochenderfer, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 12, 2024
First Posted
April 15, 2024
Study Start
September 3, 2024
Primary Completion (Estimated)
July 1, 2029
Study Completion (Estimated)
July 1, 2030
Last Updated
March 2, 2026
Record last verified: 2026-02-26
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Clinical data will be available during the study and indefinitely.
- Access Criteria
- Clinical data will be made available via subscription to BTRIS and with the permission of the study PI.
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.@@@@@@This study will comply with the NIH Genomic Data Sharing (GDS) Policy, which applies to all new and ongoing NIH IRP-funded research, as of January 25, 2015, that generates large-scale human or non-human genomic data, as well as the use of these data for subsequent research. Large-scale data include genome-wide association studies (GWAS), single nucleotide polymorphisms (SNP) arrays, and genome sequence, transcriptomic, epigenomic, and gene expression data.