A Phase I/II Study of A-dmDT390-bisFv (UCHT1) Fusion Protein in Patients with Surface CD3+ Malignant T Cell Diseases
Trial Purpose and Description
- 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.
- Define the dose-limiting toxicities (DLT) of this A-dmDT390-bisFv(UCHT1) regimen in patients with CD3+ T-cell malignant diseases
- Measure the pharmacokinetics, and immune responses to this course of bolus infusions of A-dmDT390-bisFv(UCHT1) fusion protein.
- Evaluate responses and correlate with the in vitro sensitivity of patient malignant T-cells to A-dmDT390-bisFv(UCHT1).
- 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.
- 18 and older
- 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 &ge 18 years. Patients &ge 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&rsquos Hospital, Baylor College of Medicine.
- Patients &ge 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 < 2 on Eastern Cooperative Oncology Group scale (see Appendix). Patients must have fully recovered from toxicity of prior chemotherapy or radiation therapy.
- Patients must have bilirubin < 1.5 mg/dL, transaminases < 2.5 X ULN, albumin > 3 gm/dL, creatinine < 2.0 mg/dL, adequate pulmonary function by physical exam and pulse oxometry and adequate cardiac reserve (EF > 50% normal). Patients who have had albumin ,< 3 gm/dL boosted by an albumin infusion must be observed to maintain albumin at > 3gm dL for 30 days without an additional infusion. Patients must have a normal echocardiogram without any evidence of cardiac chamber hypertrophy, dilatation or hypokinesis. The Sponsor must be provided with copies of these tests BEFORE Sponsor will approve enrollment. These may be scanned copies of lab reports sent to the Sponsor by email (firstname.lastname@example.org). In addition, the sponsor must receive a list of current medications taken by the patient before Sponsor will approve enrollment.
- 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.
- 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 the only exception being well controlled essential hypertension with a sitting B.P. of <155 systolic and <90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. A past history of the any of the following are exclusions: congestive heart failure, atrial fibrillation, pulmonary hypertension, anticoagulant drug therapy, thromboembolic events, cardiomyopathy or a myocardial infarction within the past 7 months. Referring physicians will be asked to verify that their referred patients do not have these exclusionary histories l and a copy of this verification must be sent to the Sponsor before the Sponsor will approve of enrollment.
- Pregnant or nursing women will be excluded from study.
- History of cirrhosis of the liver.
- Last Updated:
- Study HIC#: