Phase 1
N=27
T Cells Expressing a Fully-human AntiCD19 Chimeric Antigen Receptor for Treating B-cell Malignancies
Lymphoma, B-Cell · Lymphoma, Non-hodgkins
Bottom Line
View on ClinicalTrials.gov: NCT02659943 ↗Enrolled (actual)
27
Serious AEs
81.0%
Results posted
May 2021
Primary outcome: Primary: Percentage of Enrolled Participants Who Actually Get Treated — 76.9 percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Anti-cluster of differentiation 19 (CD19)-Chimeric Antigen Receptor (CAR) T cells (Biological); Cyclophosphamide (Drug); Fludarabine (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jun 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Enrolled Participants Who Actually Get Treated |
76.9 | — |
| SECONDARY Number of Participants Who Had a Best Response of Complete Remission (CR), Partial Remission (PR), Stable Disease (SD), and Progressive Disease (PD) |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With a Duration of Best Response in Months |
0; 0; 0; 2; 0; 1 | — |
| SECONDARY Number of Participants That Had Any Grade 2, 3, 4 and 5 Adverse Events |
2; 2; 1; 3; 2; 6 | — |
| SECONDARY Median Peak Chimeric Antigen Receptor (CAR) T Cells Level for Participants Treated |
42; 6; 4; 36; 6; 87 | — |
| SECONDARY Number of Participants Who Had a Second or Third Infusion of Chimeric Antigen Receptor (CAR)+ T Cells |
0; 2; 1; 0; 1; 0 | — |
| SECONDARY Number of Participants Who Had Anti-Lymphoma Activity |
3; 2; 1; 2; 1; 6 | — |
| SECONDARY Number of Participants With Evidence of Immunogenicity of the Chimeric Antigen Receptor (CAR) T-cell Product |
0; 0; 0; 0; 0; 0 | — |
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.
...
Eligibility Criteria
- INCLUSION CRITERIA:
- 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.
- Other inclusion criteria:
- 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.)
- Patients with a known history of hepatitis B or hepatitis C are not eligible due to the risk of re-activation of hepatitis after prolonged B-cell depletion due to anti-CD19 CAR T cells.
- Seronegative for hepatitis B antigen, positive hepatitis B tests can be further evaluated by confirmatory tests, and if confirmatory tests are negative, the patient can be enrolled. Patients with a known history of hepatitis B are not eligible.
- Seronegative for hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then
Data sourced from ClinicalTrials.gov (NCT02659943). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.