A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL)

This study is currently recruiting participants.
Verified April 2014 by Angimmune LLC
Sponsor:
Collaborators:
M.D. Anderson Cancer Center
Scott and White Hospital & Clinic
University of Texas Southwestern Medical Center
Yale University
Information provided by (Responsible Party):
Angimmune LLC
ClinicalTrials.gov Identifier:
NCT00611208
First received: January 25, 2008
Last updated: April 14, 2014
Last verified: April 2014
  Purpose

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.


Condition Intervention Phase
T-cell Lymphomas
T-cell Leukemia
Sezary Syndrome
Mycosis Fungoides
Cutaneous T-cell Lymphoma (CTCL)
Biological: A-dmDT390-bisFv(UCHT1) (Resimmune™)
Phase 1
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Angimmune LLC:

Primary Outcome Measures:
  • Remission status (complete, partial, stable disease, progressive disease) [ Time Frame: Time Frame: 6 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
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)
Arms Assigned Interventions
Experimental: A-dmDT390-bisFv(UCHT1)
A-dmDT390-bisFv(UCHT1) anti-T cell immunotoxin
Biological: A-dmDT390-bisFv(UCHT1) (Resimmune™)
Antibody targeting CD3 on T-cells tagged with diptheria toxin.

Detailed Description:

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.

Objectives:

  1. Evaluate the clinical responses including response rate and duration.
  2. 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.
  3. 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.
  4. Determine if correlations exist between disease stage, tumor burden, anti-DT titer and degree of T cell depletion and response rate and response duration.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have signed the current IRB approved informed consent prior to registration (see Informed Consent).
  • 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 to IIB disease are eligible provided that they have failed a systemic treatment (this includes radiation). CTCL patients with stage II to IV disease are eligible but preference will be given to patients with stage IB and stage IIB disease.
  • Patients with CD3+ T-cell malignant diseases must have failed at least one prior systemic therapy or be refractory to or choose to decline approved therapeutic agents. Note: Patients are eligible who may have had multiple prior therapies including transplant.
  • Age greater than or equal to 18 years. 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. 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.
  • Patient must have adequate pulmonary function by physical exam and pulse oximetry.
  • 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 (davidn@angimmune.com). In addition, the sponsor must receive a list of current medications taken by the patient before Sponsor will approve enrollment. A prior history of cardiac disease including arrhythmia is an absolute exclusion.
  • 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 criteria set forth in Section 3.1.
  • Inability to give informed consent because of psychiatric problems, or complicated medical problems.
  • Allergic to diphtheria toxin a component of the study drug A-dm-DT390-bisFv.
  • Serious concurrent medical problems, uncontrolled infections, or disseminated intravascular coagulopathy (DIC), hepatic cirrhosis, or chronic kidney disease.
  • CNS leukemia.
  • Preexisting cardiovascular disease. The only exception being well controlled essential hypertension with a sitting blood pressure (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 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00611208

Contacts
Contact: David Neville, MD 240-383-2589 davidn@angimmune.com

Locations
United States, Connecticut
Yale University School Of Medicine Recruiting Recruiting
New Haven, Connecticut, United States, 06520
Contact: Francine Foss, MD    203-737-5312      
Contact: Diana Irizarry, RN    (203) 737-2451    diana.irizarry@yale.edu   
Principal Investigator: Francine M. Foss, MD         
United States, Kentucky
James Graham Brown Cancer Center Not yet recruiting
Louisville, Kentucky, United States, 40202
Contact: David Figg, SC    502-562-4006    d.figg@louisville.edu   
Principal Investigator: Cesar Rodriguez, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390-8562
Contact: Adrian Avila, SC    214-648-5107    adrian.avila@utsouthwestern.edu   
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    clwilson@mdanderson.org   
Contact: Vicki Jeanis, RN    713-745-0367    vjeanis@mdanderson.org   
Principal Investigator: Madeleine Duvic, MD         
Sub-Investigator: Susan O'Brien, MD         
Scott and White Hospital & Clinic Active, not recruiting
Temple, Texas, United States, 76508
Sponsors and Collaborators
Angimmune LLC
M.D. Anderson Cancer Center
Scott and White Hospital & Clinic
University of Texas Southwestern Medical Center
Yale University
Investigators
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
  More Information

Additional Information:
Publications:
Responsible Party: Angimmune LLC
ClinicalTrials.gov Identifier: NCT00611208     History of Changes
Other Study ID Numbers: FDA IND 100712
Study First Received: January 25, 2008
Last Updated: April 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, T-Cell
Lymphoma
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Neoplasms by Histologic Type
Neoplasms
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Immunotoxins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014