Study of IPH4102 alone or in combination with chemotherapy in patients with Advanced T-cell Lymphoma.

Phase 1

Conditions: 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).
MedDRA version: 20.0Level: HLTClassification code 10002450Term: Angioimmunoblastic T-cell lymphomasSystem Organ Class: 100000004851
MedDRA version: 20.0Level: HLTClassification code 10002235Term: Anaplastic large cell lymphomas T- and null-cell typesSystem Organ Class: 100000004851
MedDRA version: 20.0Level: HLTClassification code 10028484Term: Mycoses fungoidesSystem Organ Class: 100000004851
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2018-003969-33-GB

Lead Sponsor: Innate Pharma SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 150

Inclusion Criteria

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.
Cohorts 2 and 3:
5. Relapsed and/or refractory stage IB, IIA, IIB, III, IV MF;
6. KIR3DL2 expression (Cohort 2) or non-expression (Cohort 3) in at least one skin lesion based on central evaluation by IHC;
7. Patients should have received at least two prior systemic therapies that may include monoclonal antibodies or antibody-drug conjugates;
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, except for mogamulizumab, a wash-out period of at least 8 weeks is required;
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,
-Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =2.5 X ULN.

14. Women of childbearing potential (WOCBP): Premenauposal 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. Adequate methods are described in Appendix 11;
16. Signed informed consent form prior to any protocol-specific procedures

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 75
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 75

Exclusion Criteria

1. Patients with evidence of large cell transformation (LCT) based on central histologic evaluation at screening;
2. Concomitant corticosteroid use, systemic or topical. However, stable dosage of topical steroids (maximum strength Class III according to World Health Organization (WHO) Classification of Topical Corticosteroids) and/or systemic steroids (=10 mg prednisone equivalent/day) are allowed, if patient has been on a stable dose for at least 4 weeks prior to treatment start. Inhaled steroids are allowed provided the presence of a concomitant medical condition that justifies the use;
3. Receipt of live vaccines within 4 weeks prior to treatment;
4. Central nervous system (CNS) lymphoma involvement;
5. Prior administration of IPH4102;
6. Concurrent enrollment in another clinical trial, unless it is an observational (non -
interventional) clinical study or the follow-up period of an interventional study.
7. Concomitant administration of radiotherapy or systemic anti-cancer therapy including but not restricted to: chemotherapy, biological agents, extracorporeal photopheresis (ECP) or immunotherapy;
8. Autologous stem cell transplantation less than 3 months prior to enrollment;
9. Prior allogenic transplantation;
10. Patients who have undergone major surgery = 4 weeks prior to study entry;
11. Patients with known NCI CTCAE grade 3 or higher active systemic or cutaneous viral, bacterial, or fungal infection;
12. Patients who have active Hepatitis B or C virus infection;
13. Known or tested positive for human immunodeficiency virus (HIV);
14. 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;
15. Pregnant or breastfeeding women;
16. Patients with congestive heart failure, Class III or IV, by New York Heart Association (NYHA) criteria;
17. Patients with autoimmune disease on systemic immunosuppressive treatment;
18. 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;
19. Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the clinical activity of IPH4102 (Cohorts 1-3) as a monotherapy in patients with advanced T-cell lymphoma.;Secondary Objective: To evaluate the objective response rate (ORR) of IPH4102 in patients with advanced T-cell lymphoma.;Primary end point(s): Objective Response Rate (ORR);Timepoint(s) of evaluation of this end point: ORR: until End of treatment (EOT) and during Follow-Up (FU) if applicable as per Protocol.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Quality of life (QoL) (Cohorts 1-3), ORR using blinded central review (Cohort 1), duration of response (DOR), ORR lasting at least 4 months (ORR4) (Cohorts 1-3), progression free survival (PFS), overall survival (OS), minimal residual disease (MRD).;Timepoint(s) of evaluation of this end point: Until EOT and during FU if applicable.<br>

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