Phase I/II Trial of Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy for B-cell Leukemias
National Cancer Institute (NCI)
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.
Description
Background: * Improved treatments for relapsed and refractory chronic lymphocytic leukemia/Small lymphocytic leukemia (CLL/SLL) and B-cell acute lymphoblastic leukemia or lymphoma (ALL) are needed. * T cells can be genetically modified to express chimeric antigen receptors (CARs) that specifically target malignancy-associated antigens. * Autologous T cells genetically modified to express CARs targeting the B-cell antigen CD19 have caused complete remissions in patients with leukemia or lymphoma. Responses to CAR T-cell therapy in CLL/SLL have historically been lower than in other B-cell mali…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * 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…
Interventions
- BiologicalAutologous HuCD19 ( Anti-CD19)CAR T cells
1.0x10\^6 CAR+T-cells - 12x10\^6 CAR+ T cells/kg (weight based dosing per cohort) infused on day 0
- DrugCyclophosphamide
500 mg/m\^2 IV infusion over 30 minutes on days -5, -4 and -3
- DrugFludarabine
30 mg/m\^2 IV infusion over 30 minutes administered immediately following the cyclophosphamide on days -5, -4,and -3
- DrugRituximab
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
Location
- National Institutes of Health Clinical CenterBethesda, Maryland