A Phase I/II Study of A-dmDT390-bisFv (UCHT1) Fusion Protein in Patients With Surface CD3+ Malignant T Cell Diseases
12 Years
N/A
Both
T-cell Lymphomas, T-cell Leukemia, Sezary Syndrome, Mycosis Fungoides
Trial Information
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.
Objectives:
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.
Inclusion Criteria:
- All patients must have either surface CD3+ T-cell malignant diseases diagnosed by
morphologic, histochemical or cell surface marker criteria. Patients with T-ALL must
have surface CD3 on at least 10% of the lymphoblasts as determined by flow cytometry.
CTCL patients with stage IA disease are not eligible for enrollment. CTCL patients
with stage IB disease are eligible provided that they have failed a systemic
treatment (this includes radiation). CTCL patients with stage II to IV disease are
eligible.
- Patients with CD3+ T-cell malignant diseases must have failed or be refractory to
approved therapeutic agents or choose to decline or defer, after adequate informed
consent, clinically meaningful palliative therapy.
- Age >/= 18 years.
- Patients >/= 12 years may be accrued beginning at dose level 2.5 mcg/kg, provided
that they are under the supervision of a pediatrician at Texas Children's Hospital,
Baylor College of Medicine.
- Patients >/= 12 years of age with CD3+ T-cell malignant diseases must have failed
or be refractory to approved therapeutic agents.
- Patients must have a performance status of Group scale (see Appendix). Patients must have fully recovered from toxicity of prior
chemotherapy or radiation therapy.
- Patients must have bilirubin /= 3
gm/dL, creatinine pulse oximetry and adequate cardiac reserve (EF >/= 50% normal).
- Patients must give written informed consent prior to registration (see Informed
Consent).
- Females and males must be willing to use an approved form of birth control while on
this study and for 2 weeks after completion.
Exclusion Criteria:
- Failure to meet any of the inclusion criteria.
- Inability to give informed consent because of psychiatric problems, or complicated
medical problems.
- Serious concurrent medical problems, uncontrolled infections, or disseminated
intravascular coagulopathy (DIC).
- CNS leukemia.
- Preexisting cardiovascular disease (e.g. CHF, CAD, cardiomyopathy, myocardial
infarction within past 3 months, arrhythmia) requiring ongoing treatment.
- Pregnant or nursing women will be excluded from study.
- History of congestive heart failure.
- History of cirrhosis of the liver.
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Remission status (complete, partial, stable disease, progressive disease)
Outcome Time Frame:
Time Frame: 6 years
Safety Issue:
Yes
Principal Investigator
Arthur E Frankel, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Cancer Research Institute of Scott and White Memorial Hospital
Authority:
United States: Food and Drug Administration
Study ID:
FDA IND 100712
NCT ID:
NCT00611208
Start Date:
January 2008
Completion Date:
January 2014
Related Keywords:
- T-cell Lymphomas
- T-cell Leukemia
- Sezary Syndrome
- Mycosis Fungoides
- Leukemia
- Leukemia, T-Cell
- Lymphoma
- Mycoses
- Mycosis Fungoides
- Sezary Syndrome
- Lymphoma, T-Cell
Name | Location |
|---|---|
| MD Anderson Cancer Center | Houston, Texas 77030-4096 |
| Scott and White Hospital and Clinic | Temple, Texas 76508 |
