Clinical trial NCT03902184: IPH4102 Alone or in Combination With Chemotherapy in Patients With Advanced T Cell Lymphoma
Official title: TELLOMAK: T-cell Lymphoma Anti-KIR3DL2 Therapy. An Open Label, Multicohort, Multi-center Phase II Study Evaluating the Efficacy and Safety of IPH4102/Lacutamab Alone or in Combination With Chemotherapy in Patients With Advanced T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Mycosis Fungoides/Sezary Syndrome
Lead sponsor: Innate Pharma
Sponsor class: INDUSTRY
First posted: 2019-04-03
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open label, multi-cohort, and multi-center phase II study, which evaluates the clinical activity and safety of IPH4102 in Sezary Syndrome and Mycosis fungoides as single agent.


Eligibility criteria: 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 expressing 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

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 to 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 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.

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: From the first dose until study completion, an expected average of 2 years
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) (All cohorts)
timeFrame: From first dose until study completion, an expected average of 2 years
measure: Quality of life (QoL) (All cohorts)
timeFrame: Through study completion, an expected average of 2 years
measure: pruritus (All cohorts)
timeFrame: Through study completion, an expected average of 2 years
measure: ORR using blinded central review (Cohort 1)
timeFrame: From the first dose until study completion, an expected average of 2 years
measure: Progression free survival (PFS) (All cohorts)
timeFrame: From the first dose until study completion, an expected average of 2 years
measure: Overall survival (OS) (All cohorts)
timeFrame: From the first dose until study completion, an expected average of 2 years
measure: PK parameters : Maximum Plasma Concentration of IPH4102 alone (All cohorts)
timeFrame: From the first dose until study completion, an expected average of 2 years
measure: PK parameters :Trough Concentration of IPH4102 alone (All cohorts)
timeFrame: From the first dose until study completion, an expected average of 2 years
measure: Immunogenicity of IPH4102 alone (All cohorts)
timeFrame: From the first dose until study completion, an expected average of 2 years
measure: Duration of Response (DOR)
timeFrame: From the first dose until study completion, an expected average of 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: University of California, Los Angeles (UCLA) - Medical Center
state: California
city: Orange
country: United States
facility: Irvine Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Chicago
country: United States
facility: Northwestern University The Feinberg School of Medicine
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Fairport
country: United States
facility: Universal Dermatology, PLLC68
state: New York
city: New York
country: United States
facility: Columbia University Department of Dermatology
state: New York
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh School of Medicine
state: Pennsylvania
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Fairfax
country: United States
facility: Inova Health Care Services
state: Virginia
city: Graz
country: Austria
facility: Universitätsklinik für Dermatologie Medizinische Universität Graz
city: Wien
country: Austria
facility: Medizinische Universitaet Wien
city: Brussel
country: Belgium
facility: Institut Jules Bordet
city: Leuven
country: Belgium
facility: UZ Leuven - campus Gasthuisberg
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire (CHU) de Liege
city: Bordeaux
country: France
facility: CHU de Bordeaux Saint André
city: Chambray-lès-Tours
country: France
facility: CHRU de Tours, Hôpital Trousseau
city: Créteil
country: France
facility: CHU Henri Mondor
city: Lille
country: France
facility: CHRU de Lille - Hopital Claude Huriez
city: Lyon
country: France
facility: Centre Hospitalier Lyon-Sud
city: Marseille
country: France
facility: Institut Paoli-Calmettes
city: Montpellier
country: France
facility: CHRU de Montpellier - Hopital Saint Eloi
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Rouen
country: France
facility: Hôpital Charles Nicolle-CHU de Rouen Clinique Dermatologie
city: Toulouse
country: France
facility: IUCT Oncopôle
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin
city: Bochum
country: Germany
facility: Ruhr-University Bochum
city: Frankfurt
country: Germany
facility: Universitätsklinikum Frankfurt
city: Halle
country: Germany
facility: Universitaetsklinikum Halle (Saale)
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig-Holstein Campus Kiel
city: Mannheim,
country: Germany
facility: Universitaetsmedizin Mannheim GmbH
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden
city: Muenster
country: Germany
facility: Universitaetsklinikum Muenster
city: Bologna
country: Italy
facility: Institute of Hematology "Seràgnoli", Univeristy of Bologna
city: Brescia
country: Italy
facility: ASST degli Spedali Civili di Brescia
city: Roma
country: Italy
facility: Istituto Dermopatico dell'Immacolata (IDI-IRCCS)
city: Turin
country: Italy
facility: Universita di Torino, Ospedale le Molinette
city: Gdańsk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, Klinika Dermatologii, Wenerologii i Alergologii ul. Smoluchowskiego 17
city: Skorzewo
country: Poland
facility: CET Centrum Medyczne Pratia Poznan ul. Poznanska 14
city: Warsaw
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Ukladu Chlonnego
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
city: Valencia
country: Spain
facility: Consorci Hospital General Universitari de Valencia Servicio de Dermatología
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
References: