A Phase II Study of A-dmDT390-bisFv (UCHT1) Fusion Protein in Patients with Cutaneous T Cell Lymphoma (FDA IND Number: 100712).
The goal of this clinical research study is to learn the highest safe dose of AdmDT390-bisFv (UCHT1) that can be given to patients with a CD3 positive T-cell cancer.
Disease Group: Skin
Treatment Agent: A-dmDT390-bisFv (UCHT1)
Treatment Location: Both at MDACC & outside MDACC at one or more Collaborating Sites or Institutions
Estimatated Length of Stay in Houston: None - outpatient treatment
Return Visit: 1 return follow-up visit after hospitalization thereafter, the visits are standard of care
Home Care: n/a
Primary: Evaluate the overall clinical responses including response rate and duration in a larger CTCL high-response patient population to see if is higher than current therapies (>49%). Determine the complete response rate and duration of response of A-dmDT390-bisFv(UCHT1) fusion protein in a larger CTCL high-response patient population to see if is higher than current therapies (>20%). Further define toxicities of A-dmDT390-bisFv(UCHT1) regimen in patients with CD3+ T-cell malignant diseases who have been selected to be free from preexisting cardiac disease. Determine if correlations exist between disease stage, tumor burden, anti-DT titer and degree of T cell depletion and response rate and response duration. Endpoints: Clinical response rate. Primary Toxicity profile. Duration of response-defined as time of first response to time of progression. Anti-A-dmDT390-bisFv (UCHT1) antibody titer, pretreatment and day 23. T cell depletion on day 5 or day 4 relative to the pretreatment value determined by flow cytometry of CD3+ cells in the lymphocyte gate and the measurement of the absolute lymphocyte count by CBC.
IRB Review and Approval Date: 09/24/2008
Recruitment Status: Closed
Projected Accrual: 65
1) Patients must have signed the current IRB approved informed consent
prior to registration.
2) All patients must have CTCL diagnosed by morphologic, histochemical or cell surface marker criteria with stage never exceeding IB / IIB disease and mSWAT < 50%. 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 bone marrow involvement but without lymph node involvement are eligible. Patients with a diagnosis of angioimmunoblastic T cell lymphoma are eligible. Even with lymph node involvement. Age >/= 18 years. Patients must have a performance status of < 2 on Eastern Cooperative Oncology Group scale. Patients must have fully recovered from toxicity of prior chemotherapy or radiation therapy.
3) Patients must have bilirubin < 1.5 mg/dL, transaminases < 2.5 X ULN, albumin > 3 gm/dL, creatinine < 2.0 mg/dL. 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.
4) Patient must have adequate pulmonary function by physical exam and pulse oximetry.
5) Patients must have a normal echocardiogram (EF > 50% normal) 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 reports sent to the Sponsor by email (email@example.com). In addition, the sponsor must receive a list of current medications taken by the patient before Sponsor will approve enrollment.
6) Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion.
1) Failure to meet any of the criteria set forth in the Inclusion Section.
2) Inability to give informed consent because of psychiatric problems, or complicated medical problems.
3) Allergic to diphtheria toxin a component of the study drug A-dmDT390-bisFv(UCHT1).
4) Serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (DIC), hepatic cirrhosis, or chronic kidney disease.
5) Central Nervous System leukemia.
6) Preexisting cardiovascular disease. The only exception being well controlled essential hypertension with a sitting blood pressure (B.P.) of <160 systolic and <90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. A past history of any of the following conditions is considered as exclusions to study participation: Congestive heart failure, Atrial fibrillation, Pulmonary hypertension, Anticoagulant drug therapy, Thromboembolic events, Cardiomyopathy or a myocardial infarction within the past 8 months. The PI and the Clinical Coordinator will be asked to verify that their referred patients do not have these exclusionary histories listed and a copy of this verification must be sent to the Sponsor before the Sponsor will approve of enrollment. Referring physicians will not need to sign.
7) Pregnant or nursing women will be excluded from study.
8) History of cirrhosis of the liver based on the Child-Pugh score of Class B or C are not eligible to participate.
9) Prior treatment with alemtuzumab (Campath) or similar agents or procedures that depress blood T cell counts to below 50% of the lower limit of normal.