Phase I/II clinical trial of biologic therapy with intratumoral TG1042 (Adenovirus-Interferon-gamma) in patients with Advanced Cutaneous T-Cell Lymphomas (CTCL) - Mycosis Fungoides and other CTCL - and multilesional Cutaneous B-Cell Lymphomas (CBCL)
- Conditions
- C84C84.0C85.1Mature T/NK-cell lymphomasMycosis fungoidesB-cell lymphoma, unspecified
- Registration Number
- DRKS00000219
- Lead Sponsor
- Transgene
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- All
- Target Recruitment
- 39
Patient must satisfy all of the following criteria for entry into the protocol:
- histologic proof of CTCL (mycosis fungoides and other CTCL except for Sezary Syndrom and Lymphomatoid papulosis for the 5th cohort only) or multilesional CBCL
- performance status of 0, 1, or 2 on the ECOG scale
- TNM stage Ib or higher
- failure of local tumor control by at least two first line treatments ( local steroids, PUVA, retinoids, Interferon-alpha, BCNU, radiotherapy, and antibiotics in CBCL)
- Prior treatment for diagnosis: no systemic chemotherapy or immunotherapy for metastatic or locally recurrent disease within preceeding three weeks
- minimum life expectancy >3 months
- adequate hematologic, hepatic and renal function
- hemoglobin >=10.0g/dl; WBC>=3.0 x 10e9/l; Platelet Count >=100 x 10e9/l
- Bilirubin <=2 times the upper limit of normal and serum transaminase <= 3 times the upper limit of normal
- Creatinine <= 2 times the upper limit of normal
- serum Prothrombin < 1 second greater than the upper limit of normal
- Age >= 18 years old
- Written informed consent from patients
Patients will be excluded from the study for any of the following reasons:
- history of known HIV positive serology or other active systemic infections
- serious, concomitant systemic medical disorders
- Concomitant systemic and topical corticosteroid therapy
- Participation in another experimental treatment protocol during the study period
- Major surgery in previous 3 weeks
- require or likely to require corticosteroids for intercurrent disease
- pregnancy at the entry or women who are breast feeding
- Patients without adequate protection against pregnancy during the conduct of the study and for three months after the last injection (intra-uterine device, hormonal contraception or diaphragm/condom and spermicide)
- Participation in another experimental protocol during the study within 4 weeks prior to the first examinations required by the protocol of this study
- history of substance abuse
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method * Primary Endpoint Phase I Step (Cohorts 1 to 4):<br>The primary study endpoint was the MTD. <br>Dose limiting toxicity is defined as the level at which a Grade 4 toxicity, thought to be related to treatment, is observed, or the level at which more than 2 out of 6 patients experience Grade 3 toxicity thought to be related to treatment. <br>The MTD is defined as the dose level immediately below the dose with dose limiting toxicity. In the event the MTD was not reached in the three dosing cohorts planned, the MTD was defined as 3x1011 tp, the dose administered Cohorts 3 and 4. <br>Separate analyses were performed to tabulate the incidence of less severe events at each dose level. The frequency of development of humoral immunity at each dose was noted.<br><br>* Primary Endpoint Phase II Step (Cohort 5):<br>The Global response rate according to the investigator's assessment and based on evaluation of both injected and non-injected lesions.
- Secondary Outcome Measures
Name Time Method * Secondary Endpoints Phase I Step (Cohorts 1 to 4):<br>1. Evaluation of injected lesions: Antitumor response to the adenovirus IFNg. <br>2. Biological activity: Percentage of patients with positive response as measured by immunology testing. <br>3. Safety: Frequency of AEs overall and by cohort.<br>4. Time to treatment failure, duration of response, time to relapse requiring treatment and survival time.<br><br>* Secondary Endpoints Phase II Step (Cohort 5):<br>1. Local response rate based on evaluation of injected lesions.<br>2. Distant response rate based on evaluation of non-injected lesions.<br>3. Frequency of AEs overall and by cohorts.<br>4. Time to treatment failure, duration of response, time to relapse requiring treatment,survival time.