Safety and efficacy of TBI-0301 gene-transduced donor lymphocyte infusion in patients with hematological malignancy experiencing recurrence/relapse or aggravation after allogeneic hematopoietic stem-cell transplantation
Takara Bio Inc.
077-543-7265
9
Interventional
Dose-escalation, open-label study
1
Patients:
(1)Patients with a diagnosis of relapse, recurrence or aggravation of hematological malignancy after related allogeneic stem cell transplantation
(2)Patients should be > 20 years old
(3)ECOG performance status (PS) 0 to 2
(4)No severe organ damage as measured by:
-Oxygen saturation > 93 % (non-invasive measurement is acceptable)
-AST (GOT) and ALT (GPT) < 5 X ULN
-Total bilirubin and serum creatinine < 3 X ULN
-Physically normal electrocardiogram
Donor:
(1)Original donor of hematopoietic stem cell transplantation
(2)Donor should be > 20, < 65 years old
(3)ECOG performance status (PS) 0
(4)Having a good heart, lung, liver and kidney function
-No ischemic electrocardiographic changes and no arrhythmia requiring treatment on ischemic
-Chest x-ray without evidence of active infection, and arterial oxygen saturation > 93% without oxygen administration (non-invasive measurement is acceptable)
-Serum creatinine < 1.5 mg/dL
-AST (GOT) , ALT (GPT), and total serum bilirubin < 2 X ULN
(5)Having a good hematopoietic capacity
-WBC > 3,000 /microliter, PLT > 130,000 /microliter
-Hb > 13.0 g/dL for men, 11.0 g/dL for women
Patient:
(1)Relapsed, recurrent or aggravated patients in very early after transplantation who can not expect the effect of donor lymphocyte infusion.
(2)Patients with Epstein-Barr virus- associated lymphoproliferative disorder
(3)Presence of grade II to IV acute GVHD or extensive chronic GVHD
(4)LVEF at rest < 50 %
(5)Patients with central nervous system involvement
(6)Patients with multiple malignancies
(7)Patients with active infection
(8)Ongoing GCV, acyclovir or valacyclovir administration within 24 hours before the infusion of donor lymphocytes transduced with TBI-0301
Donor:
(1)Presence of complication and medical history listed below:
-Autoimmune disease (include collagen disease)
-Phlebothrombosis, arteriosclerotic disease
-Congestive heart failure, ischemic Heart failure, cerebrovascular lesion
-Interstitial pneumonia
-Malignant tumor
(2)Diabetes uncontrollable even with regular insulin use, or uncontrollable hypertension
(3)History of grave drug allergy
(4)Pregnant or lactating women
(5)Any of the HBs antigen, HCV antibody and HIV antibody, and serological test for syphilis positivity
(6)Uncontrollable mental illness
20age old over
No limit
Both
hematological malignancy
investigational material(s)
Generic name etc : TBI-0301
INN of investigational material :
Therapeutic category code : 639 Other biological preparations
Dosage and Administration for Investigational material : Single intravenous infusion
-Safety
-Pharmacokinetics of donor lymphocytes transduced with TBI-0301
-Physical examination
-Laboratory examination
-Serology
-Retrovirus competent for replication
-FACS analysis for the expression of LNGFR
-PCR for tk
-Evaluation of the "in vivo" control of GVHD after administration of GCV
-Evaluation of GVM effect
-Evaluation of GVHD
-Frequency of administration of GCV, and ability of GCV to control GVHD
-Determination of treatment response
