adult T-cell leukemia/lymphoma
Conditions
Interventions
Lymphocytes will be collected from the subject via lymphocyte apheresis and used to manufacture TaxCTL-2402.
Phase I: TaxCTL-2402 will be administered using a 3+3 cohort dose-escalation design.
Phase
Sponsors
Kanda Yoshinobu
Eligibility
Inclusion criteria
Inclusion criteria: (1) Patients diagnosed with adult T-cell leukemia/lymphoma (ATL) who meet one of the following conditions: (a) Patients with chronic, acute, or lymphoma-type ATL who have relapsed after at least one line of chemotherapy, or who have been confirmed to have poor prognostic factors without achieving complete remission. (b) Patients with chronic, acute, or lymphoma-type ATL who have responded to initial treatment but are unable to undergo allogeneic hematopoietic stem cell transplantation due to poor prognostic factors such as age, general condition, lack of suitable donor, or physician's judgment. (2) Patients aged between 18 and 75 years at the time of informed consent. (3) Patients confirmed to possess HLA-A 24:02 at the time of provisional registration. (4) Patients whose peripheral blood lymphocyte count (excluding atypical lymphocytes and tumor cells) is >=300 /uL, and whose proportion of tumor cells in peripheral blood leukocytes is =94% without supplemental oxygen (non-invasive measurement acceptable). (b) Serum creatinine =50% on echocardiography. (7) Patients who have provided consent to continuously use a highly effective contraceptive method available in Japan (e.g., a combination of barrier method (condom) and oral combined hormonal contraceptive (containing estrogen and progestogen), intrauterine device (IUD), intrauterine hormonal release system (IUS), sterilization, etc.) from the time of informed consent until at least one year after the administration of TaxCTL-2402. (8) Patients who have provided written informed consent to participate in the study.
Exclusion criteria
Exclusion criteria: (1) Patients with uncontrolled diabetes mellitus that is difficult to manage despite continuous insulin therapy. (2) Patients with uncontrolled hypertension. (3) Patients with uncontrolled active infection. Patients whose symptoms are stable under treatment are not excluded. (4) Patients with central nervous system involvement of the tumor. (5) Patients with active second malignancy. (6) Patients who require systemic administration of corticosteroids or immunosuppressive agents exceeding 10 mg/day (prednisolone equivalent) from 14 days prior to initiation of lymphodepleting chemotherapy until the end of the study, except for: treatment of cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; use for bridging therapy (Section 6.2.1); systemic administration of <=10 mg/day (prednisolone equivalent); local administration such as inhalation or topical application. (7) Pregnant or breastfeeding women, or women who may be pregnant. (8) Patients with uncontrolled psychiatric symptoms that make study participation difficult. (9) Patients with active or chronic hepatitis B or hepatitis C. Patients with negative viral load are eligible. (a) Patients who test positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb)/hepatitis B surface antibody (HBsAb) and have hepatitis B virus (HBV) DNA levels exceeding the threshold specified in the Guidelines for the Management of Hepatitis B, 4th Edition by the Japan Society of Hepatology. However, patients whose HBV-DNA levels are below the threshold may be enrolled in the study. (b) Patients who test positive for both hepatitis C virus (HCV) antibody and HCV-RNA. However, patients who test positive for HCV antibody may be enrolled if treatment has been completed and HCV-RNA is negative. In addition, if the patient is undergoing treatment for HCV, enrollment is allowed only after treatment completion. (10) Patients who test positive for HIV antibodies. (11) Patients with creatinine clearance <30 mL/min (measured or estimated by the Cockcroft-Gault formula). (12) Patients with a history of hypersensitivity to lymphodepleting chemotherapy agents (fludarabine phosphate, cyclophosphamide). (13) Patients with a history of two or more hematopoietic stem cell transplants or a history of HLA-mismatched allogeneic hematopoietic stem cell transplantation. (14) Patients with a history of allergy or hypersensitivity to components of the investigational product, including cryoprotectants used in cell freezing. (15) Any other condition that, in the opinion of the principal investigator or sub-investigator, makes the patient unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase I: Safety Incidence of adverse events Occurrence of dose-limiting toxicity (DLT) Phase II: Efficacy Objective response rate | — |
Secondary
| Measure | Time frame |
|---|---|
| Phase I: - Objective response rate Phase II: - Type, frequency, severity, seriousness, and causality of adverse events occurring by Day 29 Common to Phase I and Phase II: - Progression-free survival - Duration of response - Relapse-free survival - Overall survival - Adverse events and device malfunctions - Clinical laboratory values and vital signs - Cytokine release syndrome | — |
Contacts
Public ContactYoshinobu Kanda
Jichi Medical University Hospital
Outcome results
None listed