T Cells Expressing a Fully-human AntiCD19 Chimeric Antigen Receptor for Treating B-cell Malignancies
T Cells Expressing a Fully-Human Anti-CD19 Chimeric Antigen Receptor for Treating B-cell Malignancies
2 other identifiers
interventional
27
1 country
1
Brief Summary
Background: The immune system fights infection and can affect cancer cells. T cells are white blood cells that are a major part of the immune system. T cells can destroy tumors. Researchers want to try to manipulate the immune system to better recognize and kill tumor cells. Objective: To test the safety of giving T cells expressing a novel fully-human anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) to people with advanced B-cell cancer. Eligibility: People ages 18-73 with a B-cell cancer that has not been controlled by other therapies. Design: Participants will be screened with: Physical exam Blood and urine tests Heart tests Bone marrow sample taken Scans in machines that take pictures Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm. The cells will be changed in a laboratory. Participants will get 2 chemotherapy drugs over 3 days. Two days later, participants will check into the hospital. They will get an intravenous (IV) catheter in an arm or chest vein. They will get the T cells through the IV in 1 infusion. After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor. Participants will have visits 6 visits for 1 year after the infusion. Some may have more follow-up visits. Participants may samples taken of spinal fluid, bone marrow, and tumors. ...
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jan 2016
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
January 20, 2016
CompletedFirst Posted
Study publicly available on registry
January 21, 2016
CompletedStudy Start
First participant enrolled
January 21, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 12, 2018
CompletedResults Posted
Study results publicly available
May 4, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
December 31, 2022
CompletedApril 19, 2023
March 1, 2023
2.4 years
January 20, 2016
February 22, 2021
March 24, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Enrolled Participants Who Actually Get Treated
Percentage of participants enrolled who received treatment with Chimeric Antigen Receptor (CAR) T cells, Fludarabine and cyclophosphamide.
4-5 weeks after the first dose
Secondary Outcomes (7)
Number of Participants Who Had a Best Response of Complete Remission (CR), Partial Remission (PR), Stable Disease (SD), and Progressive Disease (PD)
30 days post Chimeric Antigen Receptor (CAR) T-cells up to 5 years
Number of Participants With a Duration of Best Response in Months
Response duration is the time from first documentation of response, which is one month after cell infusion in all participants, until progression, initiation of off-study treatment or the last documentation on ongoing response, approx. one month -5 years.
Number of Participants That Had Any Grade 2, 3, 4 and 5 Adverse Events
Date treatment consent signed to date off study, approximately 49 months and 19 days.
Median Peak Chimeric Antigen Receptor (CAR) T Cells Level for Participants Treated
All post-infusion time-points up to at least 2 months after infusion, and CAR+ T cell analysis will continue until the CAR+ T cell level drops to undetectable levels unless a stable low level of CAR+ T cells is present at more than 3 years after infusion.
Number of Participants Who Had a Second or Third Infusion of Chimeric Antigen Receptor (CAR)+ T Cells
Participants could receive subsequent cell infusions any time 1 month after CAR T-cell infusion until 5 years after cell infusion.
- +2 more secondary outcomes
Other Outcomes (4)
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0)
Date treatment consent signed to date off study, approximately 49 months and 19 days.
MTD
Within 60 days of Chimeric Antigen Receptor (CAR) T cells infusion
Number of Participants With a Dose-Limiting Toxicity (DLT)
Within 60 days of Chimeric Antigen Receptor (CAR) T cells infusion
- +1 more other outcomes
Study Arms (6)
LEVEL 1 - Participants Who Received 0.66x10^6 CAR T Cells Only
EXPERIMENTALLEVEL 1 - participants who received - 0.66x10\^6 Chimeric Antigen Receptor (CAR) T cells only
LEVEL 1 Foll/by LEVEL 2-Participants Who Received - 0.66x10^6 CAR T Cells Foll/by 2x10^6 CAR T Cells
EXPERIMENTALLEVEL 1 followed by LEVEL 2 - participants who received - 0.66x10\^6 Chimeric Antigen Receptor (CAR) T cells followed by 2x10\^6 CAR T cells
LEVEL 1 Foll/by LEVEL 3 - Participants Who Received 0.66x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
EXPERIMENTALLEVEL 1 followed by LEVEL 3 - participant who received - 0.66x10\^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10\^6 CAR T cells
LEVEL 2 - Participants Who Received 2x10^6 CAR T Cells Only
EXPERIMENTALLEVEL 2 - participants who received - 2x10\^6 Chimeric Antigen Receptor (CAR) T cells only
LEVEL 2 Followed by LEVEL 3-Participants Who Received 2x10^6 CAR T Cells Foll/by 6x10^6 CAR T Cells
EXPERIMENTALLEVEL 2 followed by LEVEL 3 - participants who received - 2x10\^6 Chimeric Antigen Receptor (CAR) T cells followed by 6x10\^6 CAR T cells
LEVEL 3 - Participants Who Received 6x10^6 CAR T Cells Only
EXPERIMENTALLEVEL 3 - participants who received - 6x10\^6 Chimeric Antigen Receptor (CAR) T cells only
Interventions
Dose-escalation trial starting dose: 0.66x10\^6 CAR+ T cells/kg(weight based dosing)(up to a maximum dose of 18x10\^6 CAR+ T cells/kg) infuse on day 0
300 mg/m\^2 intravenous (IV) infusion over 30 minutes on days -5, -4 and -3
30 mg/m\^2 intravenous (IV) infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4,and -3
Eligibility Criteria
You may qualify if:
- Malignancy criteria:
- Patients with the following malignancies are potentially eligible: any B-cell lymphoma, and chronic lymphocytic leukemia (CLL). Patients with indolent malignancies that have transformed to diffuse large B-cell lymphoma are eligible.
- Clear cluster of differentiation 19 (CD19) expression must be uniformly detected on 75% or more of malignant cells from either bone marrow or a leukemia or lymphoma mass by flow cytometry or immunohistochemistry. These assays must be performed at the National Institutes of Health. It is preferable but not required that the specimen used for CD19 determination comes from a sample that was obtained after the patient's most recent treatment. If paraffin embedded unstained samples of bone marrow involved with malignancy or a lymphoma mass are available, these can be shipped to the National Institutes of Health (NIH) for CD19 staining; otherwise, new biopsies will need to be performed for determination of CD19 expression.
- Diffuse large B-cell lymphoma (DLBCL) patients must have received at least two prior chemotherapy-containing regimens at least one of which must have contained doxorubicin and a monoclonal antibody. Follicular lymphoma patients must have received at least 2 prior regimens including at least 1 regimen with chemotherapy. All other lymphoma and leukemia patients must have had at least 1 prior chemotherapy-containing regimen. All patients with CLL or small lymphocytic lymphoma must have had prior treatment with ibrutinib or another signal transduction inhibitor.
- Patients must have measurable malignancy as defined by at least one of the criteria below.
- Lymphoma or leukemia masses that are measurable (minimum 1.5 cm in largest diameter) by computed tomography (CT) scan is required for all diagnoses except CLL. All masses must be less than 10 cm in the largest diameter.
- For a lymphoma mass to count as measurable malignancy, it must have abnormally increased metabolic activity when assessed by positron emission tomography (PET) scan.
- For CLL and lymphoma with only bone marrow involvement no mass is necessary, but if a mass is not present, bone marrow malignancy must be detectable by flow cytometry in lymphoma and CLL.
- Greater than or equal to 18 years of age and less than or equal to age 73.
- Able to understand and sign the Informed Consent Document.
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0-1
- Room air oxygen saturation of 92% or greater
- Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
- Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus. Women of child-bearing potential are defined as all women except women who are post-menopausal or who have had a hysterectomy. Postmenopausal will be defined as women over the age of 55 who have not had a menstrual period in at least 1 year.
- Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune -competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
- +15 more criteria
You may not qualify if:
- Patients that require urgent therapy due to tumor mass effects or spinal cord compression.
- Patients that have active hemolytic anemia.
- Patients with second malignancies in addition to their B-cell malignancy are not eligible if the second malignancy has required treatment (including maintenance therapy) within the past 4 years or is not in complete remission. There are two exceptions to this criterion: successfully treated non-metastatic basal cell or squamous cell skin carcinoma.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- Active uncontrolled systemic infections (defined as infections causing fevers and infections requiring intravenous antibiotics when intravenous antibiotics have been administered for less than 72 hours), active coagulation disorders or other 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 (active atrial fibrillation is not allowed, resolved atrial fibrillation not requiring current treatment is allowed (anticoagulants count as current treatment) ), active obstructive or restrictive pulmonary disease, active autoimmune diseases such as rheumatoid arthritis.
- Patients will not be seen for screening appointments or enrolled on the protocol if they have been hospitalized within the 7 days prior to the screening appointment or the date of protocol enrollment.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- Systemic corticosteroid steroid therapy of any dose is not allowed within 14 days prior to the required leukapheresis, or the initiation of the conditioning chemotherapy regimen. Corticosteroid creams, ointments, and eye drops are allowed.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Patients with current central nervous system (CNS) involvement by malignancy (either by imaging or cerebrospinal fluid involvement or biopsy-proven).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892, United States
Related Publications (1)
Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.
PMID: 34515338DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. James N. Kochenderfer
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
James N Kochenderfer, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
January 20, 2016
First Posted
January 21, 2016
Study Start
January 21, 2016
Primary Completion
June 12, 2018
Study Completion
December 31, 2022
Last Updated
April 19, 2023
Results First Posted
May 4, 2021
Record last verified: 2023-03
Data Sharing
- IPD Sharing
- Will not share