Methods and compositions for dosing of allogeneic chimeric antigen receptor T cells
AssigneesAllogene Therapeutics, Inc., Les Laboratoires Servier
InventorsCyril Alkis Konto, Amina Zinai
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Abstract
The present disclosure concerns dosages for the treatment of human patients susceptible to or diagnosed with a disease, such as cancer. Provided are methods for administering chimeric antigen receptor (CAR)-T cells. Also provided are compositions and articles of manufacture for use in the methods.
Claims25
A method of treating a subject who has non-Hodgkin's lymphoma comprising administering to the subject allogeneic chimeric antigen receptor (CAR)-T cells (CAR-T cells) comprising an anti-human CD19 4-1BB/CD3zeta CAR, wherein the method comprises administering to the subject:
- a first lymphodepletion regimen, followed by
- at least one unit dose of 120×106 cells/dose to 360×106 cells/dose,
- wherein the anti-human CD19 4-1BB/CD3zeta CAR comprises an amino acid sequence of SEQ ID NO:
- 1.
A method of treating a subject who has non-Hodgkin's lymphoma comprising administering to the subject allogeneic chimeric antigen receptor (CAR)-T cells (CAR-T cells) comprising an anti-human CD19 4-1BB/CD3zeta CAR, wherein the method comprises administering to the subject:
- (a) a first lymphodepletion regimen, wherein
- (i) the first lymphodepletion regimen comprises administering fludarabine and cyclophosphamide, wherein fludarabine is administered at a dosage of about 30 mg/m2/day and cyclophosphamide is administered at a dosage of about 300 mg/m2/day over the course of two to three days or
- (ii) the first lymphodepletion regimen comprises administering fludarabine and cyclophosphamide and an anti-CD52 antibody, wherein fludarabine is administered at a dosage of about 30 mg/m2/day, cyclophosphamide is administered at a dosage of about 300 mg/m2/day, and anti-CD52 antibody is administered at a dosage of:
- about 10 to about 13 mg/day;
- or a total dose from about 0.3 to about 1 mg/kg, or a flat dose from about 30 to about 40 mg, from about 25 to about 60 mg or from about 100 to about 120 mg, over the course of three days, the anti-CD52 antibody comprises the amino acid sequences of SEQ ID NO:
- 8 and SEQ ID NO:
- 10, and the CAR-T cells are CD52 deficient or the CAR-T cells comprise a mixture of CD52-deficient and CD52-positive cells, followed by
- (b) at least one unit dose of 120×106 CAR-T cells/dose or 360×106 CAR-T cells/dose,
- wherein:
- the first lymphodepletion regimen is initiated between about 1 to 15 days prior to administration of the at least one unit dose, and
- the anti-human CD19 4-1BB/CD3zeta CAR comprises an amino acid sequence of SEQ ID NO:
- 1.
A method of treating a subject who has large B-cell lymphoma, follicular lymphoma or chronic lymphocytic leukemia comprising administering to the subject allogeneic chimeric antigen receptor (CAR)-T cells (CAR-T cells) comprising an anti-human CD19 4-1BB/CD3zeta CAR, wherein the method comprises administering to the subject:
- (a) a first lymphodepletion regimen, wherein
- (i) the first lymphodepletion regimen comprises administering fludarabine and cyclophosphamide, wherein fludarabine is administered at a dosage of about 30 mg/m2/day and cyclophosphamide is administered at a dosage of about 300 mg/m2/day over the course of two to three days or
- (ii) the first lymphodepletion regimen comprises administering fludarabine and cyclophosphamide and an anti-CD52 antibody, wherein fludarabine is administered at a dosage of about 30 mg/m2/day, cyclophosphamide is administered at a dosage of about 300 mg/m2/day, and anti-CD52 antibody is administered at a dosage of:
- about 10 to about 13 mg/day;
- or a total dose from about 0.3 to about 1 mg/kg, or a flat dose from about 30 to about 40 mg, from about 25 to about 60 mg or from about 100 to about 120 mg, over the course of three days, the anti-CD52 antibody comprises the amino acid sequences of SEQ ID NO:
- 8 and SEQ ID NO:
- 10, and the CAR-T cells are CD52 deficient or the CAR-T cells comprise a mixture of CD52-deficient and CD52-positive cells,
- followed by
- (b) at least one unit dose of 120×106 CAR-T cells/dose or 360×106 CAR-T cells/dose, wherein:
- the first lymphodepletion regimen is initiated between about 1 to 15 days prior to administration of the at least one unit dose, and
- the anti-human CD19 4-1BB/CD3zeta CAR comprises an amino acid sequence of SEQ ID NO:
- 1.
Dependencies are inferred from the claim text.