A Phase I/II Study of A-dmDT390-bisFv (UCHT1) Fusion Protein in Patients With Surface CD3+ Malignant T Cell Diseases
This is a Phase I/II, open-label, dose-escalation, multi-dose study of A-dmDT390-bisFv
(UCHT1) Fusion Protein, an antibody tagged with diphtheria toxin targeting CD3ε surface
membrane protein found on malignant T-cells. It is anticipated that approximately 40
patients will be enrolled in this study over two years. Patients will receive full
supportive care including transfusions of irradiated washed blood and blood products,
antibiotics, antiemetics, etc, when appropriate. However, other anti-neoplastic drugs or
hematopoietic growth factors (e.g., erythropoietin, interleukin-11, G-CSF and GM-CSF) are
not allowed. Patients will be hospitalized for 5 days (4 day administration cycle of
A-dmDT390-bisFv (UCHT1))and will be monitored two to three times weekly for 30 days.
Patients will then have a follow-up visit and testing on day 30. Patients with partial or
complete remissions will have another follow-up visit on day 60, then every three months for
1 year, followed by annual visits to assess duration of the response.
1. Determine the maximal tolerated dose (MTD) of A-dmDT390-bisFv (UCHT1) fusion protein as
a bolus infusion on days 1-4 in patients with CD3+ T-cell malignant diseases.
2. Define the dose-limiting toxicities (DLTs) of this A-dmDT390-bisFv (UCHT1) regimen in
patients with CD3+ T-cell malignant diseases.
3. Measure the pharmacokinetics, immune responses, and cytokine responses to this course
of bolus infusions of A-dmDT390-bisFv (UCHT1) fusion protein.
4. Evaluate responses and correlate with the in vitro sensitivity of patient malignant
T-cells to A-dmDT390-bisFv (UCHT1).
5. Determine the extent and kinetics of resting and malignant T-cell depletion and
repopulation in the treatment groups by flow cytometry of samples obtained from blood
and marrow aspirations.
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Remission status (complete, partial, stable disease, progressive disease)
Time Frame: 6 years
Arthur E Frankel, MD
Cancer Research Institute of Scott and White Memorial Hospital
United States: Food and Drug Administration
FDA IND 100712
|MD Anderson Cancer Center||Houston, Texas 77030-4096|
|Scott and White Hospital and Clinic||Temple, Texas 76508|