A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL)
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|ClinicalTrials.gov Identifier: NCT00611208|
Recruitment Status : Completed
First Posted : February 8, 2008
Last Update Posted : November 29, 2016
This is a Phase II clinical trial aimed at treating a subgroup of patients with cutaneous T-cell lymphoma. The drug consists of a toxin, called diphtheria toxin, which is attached to an antibody that can specifically target cancerous T-cells. Our primary objectives are, therefore, to determine the patient subgroup with respect to disease burden who best responds to this experimental drug in treating CD3 positive T cell malignancies. We will be determining how the patient and their disease respond to this research agent.
The Clinical Response Data analysis from October 2014 done at the completion of the Phase I portion of A-dmT390-bisFv(UCHT1) fusion protein clinical trial showed that there were 25 evaluable patients who received all 8 doses varying between 2.5 and 11.25 µg/kg per dose. There were responses at all the lower dose levels up to 7.5 µg/kg per dose. The overall response rate was 36% and the complete response rate was 16% (when followed for 6 months). We have identified a subgroup of CTCL patients that have a very high response rate. If we exclude patients whose mSWAT scores never exceeded 50 (50% of skin surface area times a multiplier) and who never had lymph node involvement or stage III disease we are left with 9 patients. This subgroup has an overall response rate of 89% and a complete response rate of 50% (when followed for 6 months). Of these 4 patients currently in complete remission, three are long-term responders. Two are over 6 years in duration and one over 5 years duration. These may represent cures. The long time periods in the transition from partial response to complete response without treatment, 6 months to two years, suggests that the study drug in addition to exerting a direct killing effect on tumor also functions as an immunomodulator.
|Condition or disease||Intervention/treatment||Phase|
|T-cell Lymphomas T-cell Leukemia Sezary Syndrome Mycosis Fungoides Cutaneous T-cell Lymphoma (CTCL)||Biological: A-dmDT390-bisFv(UCHT1)||Phase 2|
The purpose of this study is to further evaluate the clinical responses including response rate and duration and correlate with patient disease stage, tumor burden, anti-DT titer and degree of T cell depletion induced by A-dmDT390-bisFv(UCHT1) fusion protein for patients with surface CD3+ malignant diseases. The secondary objective is to further explore the toxicity profile of A-dmDT390-bisFv(UCHT1) fusion protein for a high-response subgroup of patients with CTCL whose disease stage has not progressed beyond stage IB/IIB with mSWAT < 50%. 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. Treatment will consist of one 4 day cycle consisting of 2 daily infusions for a total of 8 treatments given on an outpatient basis. Patients will be monitored until day 14 for signs of late drug toxicity by a daily phone call from their health care provider. Subjects will be instructed on how to monitor their own blood pressure at home and encouraged to measure and chart their daily weights that they can report to their health care provider. Off-treatment follow-up will be based upon response. Patients who experience a partial or complete remission who later relapse can receive radiation treatment of new lesions and remain on study as this course is typical of responses to an immunomodulating drug. Patients will have a follow-up visit and testing on day 37. 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. To accommodate patients, we are offering a travel reimbursement program. Due to the 4 days of consecutive infusions, we will reimburse the expense the patient would incur to travel to the participating institution for treatment.
- Evaluate the overall clinical responses including response rate and duration in a larger group of CTCL high-response patients 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 group of CTCL high-response patients to see if is higher than current therapies (>20%).
- Further define toxicities of A-dmDT390-bisFv(UCHT1) regimen in patients with CTCL who have been selected to be free from preexisting cardiac disease and never treated with Campath.
- Determine if correlations exist between disease stage, tumor burden, anti-DT titer and degree of T cell depletion and response rate and response duration.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of A-dmDT390-bisFv(UCHT1) Fusion Protein in Patients With Cutaneous T Cell Lymphoma|
|Study Start Date :||January 2008|
|Actual Primary Completion Date :||February 2015|
|Actual Study Completion Date :||November 2016|
anti-T cell immunotoxin (antibody targeting CD3 on T-cells tagged with diptheria toxin)
A-dmDT390-bisFv(UCHT1) will be administered as 60 μg/kg total given as 7.5 μg/kg/injection twice a day 4-6 hours apart for four consecutive days (days 1-4) into a free flowing IV over a period of approximately 15 minutes
Other Name: Resimmune®
- Remission status (complete, partial, stable disease, progressive disease) [ Time Frame: Time Frame: 6 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00611208
|United States, Connecticut|
|Yale University School Of Medicine Recruiting|
|New Haven, Connecticut, United States, 06520|
|United States, Kentucky|
|James Graham Brown Cancer Center|
|Louisville, Kentucky, United States, 40202|
|United States, Texas|
|University of Texas Southwestern Medical Center|
|Dallas, Texas, United States, 75390-8562|
|University of Texas MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Scott and White Hospital & Clinic|
|Temple, Texas, United States, 76508|
|Principal Investigator:||Arthur E Frankel, MD||University of Texas Southwestern Medical Center|
|Principal Investigator:||Madeleine Duvic, MD||M.D. Anderson Cancer Center|
|Principal Investigator:||Cesar Rodriguez, MD||James Graham Brown Cancer Center|