A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL)
This is a Phase II clinical trial aimed at treating patients with T-cell lymphomas (T-cell blood cancers). 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.
Clinical data pooled from the study to date identifies a subgroup of CTCL patients that had the highest treatment response rate (stage IB or IIB disease with skin coverage mSWAT score <50%). The time period from a partial response to complete response without ongoing treatment was documented at six months to two years, suggesting that this investigational medication in addition to exerting a direct killing effect on the tumor also functions as an immunomodulator. Earlier results documented and presented at the American Society of Clinical Oncology in 2012 indicated that the investigational medication, when targeting MF, resulted in a depletion rate that addressed 99% of the blood T-cells, when administered in divided doses via four days of consecutive IV infusions. Treatment of the high-response rate CTCL subgroup resulted in an overall response rate of 87.5% and a complete response rate of 50%. Two patients in this group in complete remission are post-treatment over 5-years, one patient post treatment over 4-years and one patient post-treatment over two years.
We have previously determined how much of the drug can be given to an individual, and will continue to monitor what toxicities are associated with the drug. It is anticipated that approximately 13 patients will be enrolled in this study over the next year. Patients will receive full supportive care during the course of the study. 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. Depending on the center chosen, participation in the study will be done on an in-patient basis for 4 consecutive days or an out-patient basis for 4 consecutive days of study medication into a free flowing IV over a period of approximately 15 minutes. Vital signs including blood pressure, pulse, temperature, respirations and pulse oximetry will be measured every fifteen minutes for one hour and then every hour for five hours after each infusion, and then every 4 hours while hospitalized. Patients will receive additional follow up care via phone. These will be conducted as part of the patient's standard of care. Re-treatment of re-occurring tumor lesions by radiation is a possibility and will be determined by the Principal Investigator.
Cutaneous T-cell Lymphoma (CTCL)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I/II Study of A-dmDT390-bisFv(UCHT1) Fusion Protein in Patients With Surface CD3+ Malignant T Cell Diseases|
- Remission status (complete, partial, stable disease, progressive disease) [ Time Frame: Time Frame: 6 years ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2008|
|Estimated Study Completion Date:||July 2018|
|Estimated Primary Completion Date:||July 2014 (Final data collection date for primary outcome measure)|
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 CD3 ε surface membrane protein found on malignant T-cells. 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. 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 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.
- Evaluate the clinical responses including response rate and duration.
- Determine the response rate and duration of response of A-dmDT390-bisFv(UCHT1) fusion protein as a bolus infusion on days 1-4 in patients with CD3+ T-cell malignant diseases.
- 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.
|Contact: David Neville, MDfirstname.lastname@example.org|
|United States, Connecticut|
|Smilow Cancer Center at Yale-New Haven||Recruiting|
|New Haven, Connecticut, United States, 06510|
|Contact: Diana Irizarry, RN 203-737-2451 email@example.com|
|Principal Investigator: Francine M. Foss, MD|
|United States, Texas|
|University of Texas Southwestern Medical Center||Recruiting|
|Dallas, Texas, United States, 75390-8562|
|Contact: Adrian Avila, SC 214-648-5107 firstname.lastname@example.org|
|Principal Investigator: Arthur E Frankel, MD|
|University of Texas MD Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Carol Wilson, RN 713-563-4655 email@example.com|
|Contact: Vicki Jeanis, RN 713-745-0367 firstname.lastname@example.org|
|Principal Investigator: Madeleine Duvic, MD|
|Sub-Investigator: Susan O'Brien, MD|
|Scott and White Hospital & Clinic||Not yet recruiting|
|Temple, Texas, United States, 76508|
|Contact: Sheila R. Bass, RN 254-724-5243|
|Principal Investigator:||Arthur E Frankel, MD||University of Texas Southwestern Medical Center|
|Principal Investigator:||Francine M Foss, MD||Yale University|
|Principal Investigator:||Madeleine Duvic, MD||M.D. Anderson Cancer Center|