Status and phase
Conditions
Treatments
About
Background:
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) 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.
Eligibility:
People aged 18 years and older with CLL or SLL 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.
Full description
Background:
Primary objective, Phase I:
-Determine the safety of administering a novel conditioning regimen and T cells expressing the Hu19-CD828Z CAR to participants with advanced CLL.
Primary objective, Phase II:
-Determine the overall response rate (ORR) of a novel conditioning regimen and T cells expressing the Hu19-CD828Z CAR for participants with advanced CLL.
Eligibility:
Design:
Enrollment
Sex
Ages
Volunteers
Inclusion and exclusion criteria
INCLUSION CRITERIA:
Malignancy criteria
Histologically confirmed participants with either CLL or SLL will be eligible.
Demonstration of CD19 expression on CLL/SLL, as assessed by the NCI Laboratory of Pathology or NIH Department of Laboratory Medicine Hematopathology section.
CD19 expression must be uniform meaning no populations of clearly CD19-negative CLL/SLL cells are observed.
Participants must have received prior systemic therapy. The last dosage of systemic therapy (including corticosteroids) must be at least 14 days prior to the first dose of rituximab.
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 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.
All participants must have measurable malignancy as defined by at least one of the criteria below.
Other inclusion criteria:
Age >= 18 years.
Performance status (ECOG) 0-1.
Participants must have adequate organ and marrow function as defined below:
ANC >= 1,000/mcL without the support of filgrastim or other growth factors in the 10 days prior to enrollment
platelets >= 50,000/mcL without transfusion support
hemoglobin >= 8 g/dL
total bilirubin <= 2.0 mg/dL
ALT or AST Serum ALT and AST less or equal to 3 times the upper limit of the institutional normal unless liver involvement by malignancy is demonstrated. If liver involvement with malignancy is detected, ALT and AST must be less than or equal to 5 times the upper limit of normal
Serum Creatinine Serum creatinine levels < 1.5 X institutional ULN. Participants with serum creatinine >= 1.5 X institutional ULN may participate if serum creatinine eGFR is >=50 mL/min/1.73m^2 by 2021 CKD-EPI equation.
B cells must make up less than 90% of blood lymphocytes on a lymphocyte phenotyping profile TBNK at the time of enrollment.
Room air oxygen saturation of 92% or greater
Participants of child-bearing or child-fathering potential must be willing to practice abstinence or highly effective contraception from the time of enrollment on this study and for 12 months after receiving the protocol treatment, or until CAR T cells are no longer detectable in the blood, whichever is later.
Participants must agree not to donate eggs for 12 months after receiving the protocol treatment, or until CAR T cells are no longer detectable in the blood, whichever is later.
Participants who are breastfeeding must be willing to cease breastfeeding from time of enrollment until 6 months after receiving treatment, or until CAR T cells are no longer detectable in the blood, whichever is later.
Participants must have a negative blood PCR test for hepatitis B DNA. If hepatitis B DNA (PCR) testing is not available, participants must have a negative hepatitis B surface antigen and negative hepatitis B core antibody test.
Participants must have a negative blood PCR test for hepatitis C RNA. Only if Hepatitis C PCR testing is not available in a timely manner, participants must have a negative Hepatitis C antibody test.
Cardiac ejection fraction of greater than or equal to 50% by echocardiography and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 30 days prior to treatment start.
All participants must have the ability to understand and willingness to sign a written informed consent.
All participants must be willing to undergo mandatory biopsies during the study. A bone marrow biopsy will be required prior to the chemotherapy and CAR T-cell infusion. Another bone marrow biopsy will be required approximately 14 days after CAR T-cell infusion.
EXCLUSION CRITERIA:
Primary purpose
Allocation
Interventional model
Masking
66 participants in 2 patient groups
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Central trial contact
Micaela A Ganaden, R.N.; Jennifer N Brudno, M.D.
Data sourced from clinicaltrials.gov
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