A Phase IB Study of A-dmDT390-bisFv (UCHT1) Fusion Protein in Patients with Surface CD3+ Malignant T Cell Diseases

Study ID
STU 032013-027

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

Contact
Joyce Bolluyt
214-648-7007
joyce.bolluyt@utsouthwestern.edu

Principal Investigator
Arthur Frankel

Summary

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) Resimmune[TM] fusion protein for patients with surface CD3+ malignant diseases.

a-dmDT390-bisFv (uCHT1) Resimmune[TM]will be administered twice a day with a 4-6 hour interval between doses for four consecutive days (days 1-4) 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 min for one hour and then every hour for five hours after administration and then q4h while hospitalized.

The a-dmDT390-bisFv (uCHT1) Resimmune[TM] dose will be 60 [MiCRo-SYMBoL]g/kg total given as 7.5 [MiCRo-SYMBoL]g/kg/injection twice a day given 4-6 hours apart for four consecutive days (days 1-4) into a free flowing iV over a period of approximately 15 minutes. The doses on day 2, 3, and 4 can only be given in the absence of grade 3 non-hematologic toxicity.

The Subjects will be treated on an outpatient basis for a 4 day administration cycle of a-dmDT390-bisFv(uCHT1) Resimmune[TM]. on day 1 an intravenous line started with 5% dextrose/0.45% naCl at 1 L/day on days 1-4, and run slowly to minimize salt loading. Prior to each of the eight infusions of study drug, the patients will receive premedication with diphenhydramine 50 mg Po, ranitidine 150 mg Po and acetaminophen 650mg. any iV line used for the drug infusion, should be checked for blood return 15 minutes prior to the infusion. if indicated by the investigator an optional premedication of iV corticosteroids 50-100 mg hydrocortisone can be given. Prophylactic anti-infectives will be given for two weeks starting on day 1: acyclovir 400 mg Po twice a day; Bactrim DS (SMZ-TMP DS 800-160 mg) 1 tablet Po three times a week (Monday, Wednesday and Friday). The subjects will also be monitored for cytomegalovirus (CMV) and epstein Barr Virus (eBV) polymerase chain reaction (PCR). eBV PCR will be performed at screening, day 5, day 10, and day 23. CMV PCR will be performed at screening, day 10, day 23, and day 37. Subjects will receive the same treatments on days 2-4 if there is no drug-related grade 3 non-hematologic toxicity. if patients are allergic to any of the above mentioned medications an appropriate substitution may be made.

endpoints:
1. Clinical response rate.
2. Primary Toxicity profile.
3. Duration of response-defined as time of first response to time of progression.
4. anti-a-dmDT390-bisFv (uCHT1) Resimmune[TM]pretreatment antibody titer.
5. 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


Participant Eligibility

1. All subjects must have either surface CD3+ T-cell malignant diseases diagnosed by morphologic, histochemical or cell surface marker criteria. Subjects with T-ALL must have surface CD3 on at least 10% of the lymphoblasts as determined by flow cytometry. Cutaneous T-Cell Lymphoma (CTCL) subjects 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 subjects with stage II to IV disease are eligible.

2. Subjects with CD3+ T-cell malignant diseases must have failed at least one prior systemic therapy or be refractory to approved therapeutic agents or choose to decline or defer, after adequate informed consent, clinically meaningful palliative therapy. NOTE: They may have multiple prior therapies including transplant and are eligible.


3. Age 18 years and over.

4. Patients must have a performance status of < 2 on Eastern Cooperative Oncology Group scale. Subjects must have fully recovered from toxicity of prior chemotherapy or radiation therapy.

5. Subjects 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). Subjects 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. Subjects 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 (davidn@angimmune.com). In addition, the sponsor must receive a list of current medications taken by the patient before Sponsor will approve enrollment.

6. Patients must give written informed consent prior to registration.

7. Females and males must be willing to use an approved form of birth control while on this study and for 2 weeks after completion.

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