Phase I/II study of adoptive immunotherapy using cytotoxic T cells specific for minor histocompatibility antigen restricted to hematopoietic cells for patients with high-risk leukemia that relapsed following allogeneic hematopoietic stem cell transplantation

UMIN ID: C000000162

Registered date:12/09/2005

Basic Information

• Health condition(s) or Problem(s) studied: 1) RAEB, CMML 2) AML or ALL in induction failure or beyond first remission 3) Ph/p190-positive ALL at any stage 4) imatinib-resistant CML
• Date of first enrollment: 2004/04/01
• Target sample size: 30
• Countries of recruitment: Japan
• Study type: Interventional
• Intervention(s): Upon relapse, immunosuppressive drugs are withdrawn. If necessary, cytoreductive chemotherapy may be administered before adoptive immunotherapy. In the absence of unacceptable toxicity due to cessation of immunosuppressive drugs or chemotherapy, patients receive weekly CTL clone infusion 5 times. Initial dose is 3 million cells/m2. Cell numbers are escalated by 3.2 times each infusion. If anti-leukemic effect is observed, dose escalation is suspended.

Outcome(s)

• Primary Outcome: 1) Determine the toxicity including grade II or more acute GVHD from the initiation of T cell infusion to 2 weeks after the last infusion and extensive chronic GVHD. 2) Determine the non-hematological toxicity (grade 3 or 4) from the initiation of T cell infusion to 2 weeks after the last infusion.
• Secondary Outcome: 1) Determine the CR rate from the initiation of T cell infusion to 2 weeks after last infusion. 2) Determine the persistence and kinetics of transfused T cells in vivo from the initiation of T cell infusion to 2 weeks after last infusion. 3) Determine the T cell number that can be infused safely.

Key inclusion & exclusion criteria

• Age minimum: 18years-old
• Age maximum: 65years-old
• Gender: Male and Female
• Exclude criteria: 1) CNS involvement or uncontrollable extramedullary disease. 2) Severe infections (including active tuberculosis) or double cancer 3) Patients with organ toxicity as follows: (a) T.Bil >= 1.5 mg/dl, (b) GOT, GPT >= 2.5 x N (upper normal limit of individual institutions), (c) serum creatine >= 1.5 x N, 24-h Ccr =< 60 ml/min, (d) PaO2 < 60 mmHg, (e) ejection fraction <50%, (f) abnormal ECG (ischemic change or arrhythmia requiring treatment) 4) Uncontrolable HT 5) One of the following: positive HBs antigen, seropositive to HCV, seropositive to HIV, seropositive to HTLV-1, seropositive to STS 6) Patients treated with major tranquilizer or antidepressant 7) Patients inappropriate for transplantation with reasons other than above.

Related Information

• Primary Sponsor: Aichi Cancer Center
• Source(s) of Monetary Support: Ministry of Health, Labour and Welfare