E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced T-Cell Lymphomas (TCL), i.e. Cutaneous T Cell Lymphomas (CTCL) CTCL subtypes under investigation: relapsed/refractory Sézary Syndrome (SS), stage IB to IV Mycosis Fungoides (MF). AngioImmunoblastic T-cell Lymphoma (AITL), Anaplastic Large Cell Lymphoma (ALCL). |
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E.1.1.1 | Medical condition in easily understood language |
Rare types of cancers of the immune system |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10002450 |
E.1.2 | Term | Angioimmunoblastic T-cell lymphomas |
E.1.2 | System Organ Class | 100000004851 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10002235 |
E.1.2 | Term | Anaplastic large cell lymphomas T- and null-cell types |
E.1.2 | System Organ Class | 100000004851 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10028484 |
E.1.2 | Term | Mycoses fungoides |
E.1.2 | System Organ Class | 100000004851 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the clinical activity of IPH4102 (Cohorts 1-3) as a monotherapy in patients with advanced T-cell lymphoma. |
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E.2.2 | Secondary objectives of the trial |
-To evaluate the objective response rate (ORR) of IPH4102 in patients with advanced T-cell lymphoma. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- SS patients (Cohort 1): 1. Relapsed and/or refractory stage IVA, IVB SS who have received at least two prior systemic therapies; 2. Prior treatment with mogamulizumab; 3. Patients should have blood stage B2 at screening based on central evaluation by flow cytometry; 4. Feasibility of obtaining at least one skin biopsy at screening;
- MF patients (Cohorts 2 and All comers): 5. Relapsed and/or refractory stage IB, IIA, IIB, III, IV MF; 6. Only for Cohort 2: KIR3DL2 expression in at least one skin lesion based on central evaluation by IHC; 7. Patients should have received at least two prior systemic therapies; 8. Feasibility of obtaining at least one skin biopsy at screening;
- Additional inclusion criteria applicable to all cohorts: 9. Male or Female, at least 18 years of age; 10. ECOG performance status ≤2; 11. The patient must have a minimum wash-out period of 3 weeks between the last dose of prior systemic therapy and the first dose of IPH4102, 12. Patients should have recovered from all non-hematological adverse events related to prior therapy to ≤ grade 1 except for alopecia; 13. Adequate baseline laboratory data: Hematology: - Hemoglobin >9 g/dL, - Absolute neutrophil count (ANC) ≥1,500/µL, - Platelets ≥100,000/µL, Biochemistry: - 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, - Creatinine clearance ≥ 30 mL/min, calculated with the Cockcroft & Gault formula, -Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤2.5 X ULN. 14. Women of childbearing potential (WOCBP): Premenopausal females who had at least one menstrual cycle in the past 12 months and capable to become pregnant. They must have a negative serum beta-HCG pregnancy test result within seven days from start of treatment; 15. Women of childbearing potential and all men (and their female partners of childbearing potential) who are sexually active must agree to use adequate method of contraception at study entry, during treatment and for at least 9 months (270 days) following the last dose of study drug. 16. Signed informed consent form prior to any protocol-specific procedures.
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E.4 | Principal exclusion criteria |
1. Patients with evidence of large cell transformation (LCT) based on central histologic evaluation at screening; 2. Receipt of live vaccines within 4 weeks prior the treatment; 3. Central nervous system (CNS) lymphoma involvement; 4. Prior administration of IPH4102; 5. Concurrent enrollment in another clinical trial, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study; 6. Autologous stem cell transplantation less than 3 months prior to enrollment; 7. Prior allogenic transplantation; 8. Patients who have undergone major surgery ≤ 4 weeks prior to study entry; 9. Patients with known NCI CTCAE grade 3 or higher active systemic or cutaneous viral, bacterial, or fungal infection; 10. Patients who have active Hepatitis B virus infection determined as HBsAg positive and/or Hepatitis C virus infection determined as detection of HCV RNA in serum or plasma by a sensitive quantitative molecular method; 11. Known or tested positive for human immunodeficiency virus (HIV); 12. Patients with a history of other malignancies during the past five years apart from the disease subject of this study. The following are exempt from the five-year limit: non-melanoma skin cancer, lymphomatoid papulosis, resected thyroid cancer, biopsy-proven cervical intraepithelial neoplasia, Ductal carcinoma in situ (DCIS) or cervical carcinoma in situ; 13. Pregnant or breastfeeding women; 14. Known clinically significant cardiovascular disease or condition, including: • Class III or IV cardiovascular disease according to the New York Heart Association (NYHA) Functional Classification; • Any uncontrolled arrhythmia (per the investigator's discretion); • Uncontrolled hypertension (per the investigator's discretion). 15. Patients with autoimmune disease on systemic immunosuppressive treatment; 16. Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment and/or comply with study protocol; 17. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document.
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E.5 End points |
E.5.1 | Primary end point(s) |
Objective Response Rate (ORR) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
ORR: until End of treatment (EOT) and during Follow-Up (FU) if applicable as per Protocol. |
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E.5.2 | Secondary end point(s) |
To characterize the safety and tolerability of IPH4102; To assess Quality of life (QoL); To evaluate other clinical activity endpoints: ORR using blinded central review (Cohort 1 only), duration of response (DOR), progression free survival (PFS) and overall survival (OS); To evaluate the pharmacokinetics (PK) and immunogenicity of IPH4102. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Until EOT and during FU if applicable.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
United States |
Austria |
Belgium |
France |
Germany |
Italy |
Poland |
Spain |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |