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) and Peripheral T Cell Lympomas (PTCL).CTCL subtypes under investigation: relapsed/refractory Sézary Syndrome (SS), stage IB to IV Mycosis Fungoides (MF).Relapsed/refractory PTCL subtypes under investigation: PTCL-Not Otherwise Specified (PTCL-NOS), AngioImmunoblastic T-cell Lymphoma(AITL), Anaplastic Large Cell Lymphoma (ALCL).
MedDRA version: 20.0Level: HLTClassification code 10034622Term: Peripheral T-cell lymphomas NECSystem Organ Class: 100000004851
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-ES

Lead Sponsor: Innate Pharma SA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 250

Inclusion Criteria

Cohort 1:
1.Patients with relapsed/refractory SS who have received at least 2 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 1 skin biopsy at screening.
Cohorts 2 and 3:
5.Patients with stage IB to IV MF;
6.KIR3DL2 expression (Cohort 2) or non-expression (Cohort 3) in at least 1 skin lesion;
7.Patients should have received at least 2 prior systemic therapies that may include biological agents;
8.Feasibility of obtaining at least 1 skin biopsy at screening;
9.Adequate baseline laboratory data: Hematology: CD4+ T-cells =200/µL.
Cohorts 4 and 5:
10.Patients with relapsed/refractory PTCL of the following subtypes: PTCL-NOS, angioimmunoblastic T-cell lymphoma (AITL), or anaplastic large cell lymphoma (ALCL);
11.KIR3DL2 expression (Cohort 4) or non-expression (Cohort 5) based on 1 involved lymph node;
12.Patients should have received at least 1 prior systemic therapy including an anthracycline-based chemotherapy. Patients who are not eligible for treatment with anthracycline based therapy are eligible for inclusion provided that they were treated with at least one prior systemic therapy;
13.Presence of at least 1 target lesion on PET/CT scan at screening;
14.Feasibility of obtaining 1 lymph node biopsy at screening.
All cohorts:
15.Male or Female, at least 18 years of age;
16.ECOG performance status =2;
17.The patient must have a minimum wash-out period of 4 weeks between the last dose of prior systemic therapy (8 weeks for biological agents) and the first dose of IPH4102
18.Patients should have recovered from all adverse events related to prior therapy to = grade 1;
19.Adequate baseline laboratory data
20.Women of childbearing potential (WOCBP) must have a negative serum beta-HCG pregnancy test result within seven days from start of treatment;
21.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.
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 125
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 125

Exclusion Criteria

Cohorts 1 to 3:
1.Patients with evidence of large cell transformation (LCT) based on central histologic evaluation.
Cohorts 4 and 5:
2.Prior administration of gemcitabine and/or oxaliplatin;
3.Presence of grade 2 neurotoxicity or higher.
All Cohorts:
4.Known central nervous system (CNS) lymphoma;
5.Prior administration of IPH4102;
6.Concomitant administration of radiotherapy or systemic anti-cancer therapy including but not restricted to: chemotherapy, biological agents or immunotherapy;
7.Autologous stem cell transplantation less than 3 months prior to enrollment;
8.Prior allogenic transplantation;
9.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;
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.Patients who are known to be HIV-positive;
14.Patients with a history of other malignancies during the past 5 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 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 known active autoimmune disease;
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 alone (Cohorts 1-3) or in combination with GEMOX chemotherapy (Cohorts 4 and 5) in patients with advanced T-cell lymphoma.;Secondary Objective: -To characterize the safety and tolerability of IPH4102 alone (Cohorts 1-3) or in combination with GEMOX chemotherapy (Cohorts 4 and 5);<br>-To further characterize the clinical activity of IPH4102 alone or in combination with GEMOX chemotherapy;<br>-To evaluate the pharmacokinetics (PK) and immunogenicity of IPH4102 alone or in combination with GEMOX chemotherapy.;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.

Related Trials