Cutaneous T-cell lymphoma
Conditions
Interventions
Enrolment of approximately 60 patients with KIR3DL2-positive CTCL in two
sequential study portions:
_dose-escalation portion: sequential enrolment of approximately 40 CTCL
patients in 10 Dose cohort
0.001
0.010
0.050
0.200
0.750
3.0
6.0
10.0 mg/kg)
_cohort expansion portion: enrolment of 2 x 10 patients in 2 CTCL subtype
cohorts emerging from the dose escalation portion (expected: SS and tMF)
Sponsors
Innate Pharma
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Note: In the dose escalation portion, all subtypes of relapsed/refractory CTCL will be allowed, in the cohort expansion portion inclusion of specific CTCL subtypes is planned according to findings of the dose escalation portion (e.g. tMF and SS). 1) Patients with relapsed/refractory, biopsy-proven primary cutaneous T-cell lymphoma who have received at least two previous standard systemic therapies and, if MF/SS, is stage IBIVB at study entry. Total skin electron beam irradiation is not regarded as systemic therapy. 2) Centrally assessed KIR3DL2 expression on tumor cells. A blood sample and skin biopsies will be obtained within 4 weeks of beginning study medication, for assessment of KIR3DL2 by flow cytometry or immunohistochemistry (IHC). KIR3DL2 expression on *5% malignant cells in skin or on *5% malignant cells in blood (Immunophenotype: CD3+CD4+CD8-) is regarded as KIR3DL2 positive. If a patient has different lesion morphology (patch, plaque, tumor), a biopsy will be obtained from each morphologic lesion and KIR3DL2-positivity in at least one lesion will be sufficient for enrolment of a patient. 3) Patients must have the following minimum wash-out from previous treatments: - *12 weeks for total skin electron beam irradiation, - *4 weeks for monoclonal antibodies (* 8 weeks for alemtuzumab), - *3 weeks for local radiation therapy, systemic cytotoxic anticancer therapy, treatment with other anti-neoplastic investigational agents, - *3 weeks for systemic retinoids, interferons, vorinostat, romidepsin, fusion proteins, - *3 weeks for phototherapy, - *2 weeks for topical therapy (including steroids, retinoids, nitrogen mustard or imiquimod). Topical steroids (maximum strength: Class III according to World Health Organization Classification of Topical Corticosteroids) and/or oral steroids (* 10 mg prednisone equivalent/day) are allowed, if the patient has been on a stable dose with stable disease for at least 1 month prior to study entry. 4) At least 18 years of age. 5) ECOG performance status of * 2. 6) Adequate baseline laboratory data: hemoglobin >9 g/dL, absolute neutrophil count (ANC) *1,000/*L, CD4+ T-cells *200/*l, platelets *50,000/*L, bilirubin *1.5 X upper limit of normal (ULN) or *3 X ULN for patients with Gilbert's disease, serum creatinine *1.5 X ULN, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) *3 X ULN. 7) Women of childbearing potential (WOCBP) must have a negative serum beta-HCG pregnancy test result within seven days of treatment and must practice an effective method of contraception during treatment and for at least 9 months (270 days) following the last dose of study drug. 8) Female patients who are post-menopausal or surgically sterile. 9) Male patients who agree to practice effective barrier contraception. 10) Ability to understand and the willingness to sign a written informed consent document. 11) No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Exclusion criteria
Exclusion criteria: 1) Patients with limited disease (if MF/SS: stages IA), or central nervous system (CNS) disease. 2) Clinical relevant AEs or laboratory results related to previous anti-neoplastic therapy have not resolved to a NCI-CTCAE grade *1. 3) Concomitant corticosteroid use, systemic or topical, for treatment of skin disease. However, topical steroids (maximum strength: Class III according to World Health Organization Classification of Topical Corticosteroids) and/or oral steroids (*10 mg prednisone equivalent/day) are allowed, if patient has been on a stable dose with stable disease for at least 4 weeks prior to study entry. 4) Patients who have undergone major surgery
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Occurrence of DLT DLT is defined as the occurrence of any _grade *3 non hematologic or hematologic toxicity lasting for *8 days, except lymphopenia, or _grade *4 symptoms judged to be consistent with an Infusion Related Reaction (IRR)/cytokine release syndrome without premedication or _grade *3 symptoms judged to be consistent with recurrent IRR/cytokine release syndrome despite premedication or _grade *3 tumor lysis syndrome MTD will be defined as the highest dose level where none out of 3 or no more than 1 out of 6 patients experiences a DLT within 14 days after first IPH4102 administration 2. Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs) Safety of IPH4102 is assessed using the CTCAE grading system (version 4.03 of June 14, 2010) and coded according to MedDra. A Safety Committee will evaluate the safety data in the dose escalation portion and during the cohort expansion portion. | — |
Secondary
| Measure | Time frame |
|---|---|
| Safety endpoints: _Adverse Events (AEs) _Serious Adverse Events (SAEs) _Drug related AEs _Drug related SAEs Efficacy endpoints: _Overall Objective Response Rate (complete response (CR) + partial response (PR)) _Response (CP/PR) duration _Progression-free survival (PFS) Response assessment will be performed according to the Global Response Score of the International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) criteria for MF/SS. Cutaneous involvement will be assessed with the Modified Severity Weighed Assessment Tool (mSWAT) or for subcutaneous tumors by appropriate imaging. Independent confirmation of the response may be requested by the Sponsor. _Pruritus severity changes For pruritus assessment a visual analogue scale (VAS) and a standardized skin-specific questionnaire (SkinDex29) will be used. PK endpoints: _Maximum and trough concentration of IPH4102 at each administration _Area under the curve from time 0 to day 7 (AUC day 0-7) for the first and fourth administration _Accumulation index (in terms of ratio of Cmax and of AUC 0-7 days between the fourth and first administration) _Presence of Human Anti-Drug Antibodies (ADAs) and if present, assessment of their neutralizing potential. | — |
Countries
Netherlands
Outcome results
None listed