IPH4102 Alone or in Combination With Chemotherapy in Patients With Advanced T Cell Lymphoma

Lymphoma, T-Cell, Cutaneous Clinical Trial

— TELLOMAK  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03902184
• Other study ID #: IPH4102-201
• Secondary ID: 2018-003969-33
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 22, 2019
• Est. completion date: October 31, 2024

Study information

• Verified date: July 2023
• Source: Innate Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 170
• Est. completion date: October 31, 2024
• Est. primary completion date: October 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Cutaneous
• Lymphoma, T-Cell, Peripheral
• Mycoses
• Mycosis Fungoides
• Mycosis Fungoides/Sezary Syndrome
• Sezary Syndrome

Intervention

Biological:
• IPH4102
Patients will receive a flat dose of 750mg

Locations

Country	Name	City	State
Austria	Universitätsklinik für Dermatologie Medizinische Universität Graz	Graz
Austria	Medizinische Universitaet Wien	Wien
Belgium	Institut Jules Bordet	Brussel
Belgium	UZ Leuven - campus Gasthuisberg	Leuven
Belgium	Centre Hospitalier Universitaire (CHU) de Liege	Liège
France	CHU de Bordeaux Saint André	Bordeaux
France	CHRU de Tours, Hôpital Trousseau	Chambray-lès-Tours
France	CHU Henri Mondor	Créteil
France	CHRU de Lille - Hopital Claude Huriez	Lille
France	Centre Hospitalier Lyon-Sud	Lyon
France	Institut Paoli-Calmettes	Marseille
France	CHRU de Montpellier - Hopital Saint Eloi	Montpellier
France	Hôpital Saint-Louis	Paris
France	Hôpital Charles Nicolle-CHU de Rouen Clinique Dermatologie	Rouen
France	IUCT Oncopôle	Toulouse
Germany	Charite - Universitaetsmedizin Berlin	Berlin
Germany	Ruhr-University Bochum	Bochum
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitaetsklinikum Halle (Saale)	Halle
Germany	Universitaetsklinikum Schleswig-Holstein Campus Kiel	Kiel
Germany	Universitaetsmedizin Mannheim GmbH	Mannheim,
Germany	Johannes Wesling Klinikum Minden	Minden
Germany	Universitaetsklinikum Muenster	Muenster
Italy	Institute of Hematology "Seràgnoli", Univeristy of Bologna	Bologna
Italy	ASST degli Spedali Civili di Brescia	Brescia
Italy	Istituto Dermopatico dell'Immacolata (IDI-IRCCS)	Roma
Italy	Universita di Torino, Ospedale le Molinette	Turin
Poland	Uniwersyteckie Centrum Kliniczne, Klinika Dermatologii, Wenerologii i Alergologii ul. Smoluchowskiego 17	Gdansk
Poland	CET Centrum Medyczne Pratia Poznan ul. Poznanska 14	Skorzewo
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Klinika Nowotworow Ukladu Chlonnego	Warsaw
Spain	Hospital Clinic Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Consorci Hospital General Universitari de Valencia Servicio de Dermatología	Valencia
Spain	Hospital Universitari i Politecnic La Fe	Valencia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Northwestern University The Feinberg School of Medicine	Chicago	Illinois
United States	Inova Health Care Services	Fairfax	Virginia
United States	Universal Dermatology, PLLC68	Fairport	New York
United States	MD Anderson Cancer Center	Houston	Texas
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	University of California, Los Angeles (UCLA) - Medical Center	Los Angeles	California
United States	Columbia University Department of Dermatology	New York	New York
United States	Irvine Medical Center	Orange	California
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh School of Medicine	Pittsburgh	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Stanford University	Stanford	California
United States	Moffitt Cancer Center	Tampa	Florida
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Innate Pharma

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  France,  Germany,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective Response Rate (ORR)	Using the Olsen (2011, JCO) criteria (All cohorts)	From the first dose until study completion, an expected average of 2 years
Secondary	Incidence of Treatment-Emergent Adverse Events (Safety and tolerability) (All cohorts)	patients with treatment-related adverse events as assessed by CTCAE v5.0	From first dose until study completion, an expected average of 2 years
Secondary	Quality of life (QoL) (All cohorts)	Using the Skindex29 questionnaire to assesse the effects of skin disease on quality of life in three domains: Symptoms, Emotions, and Functioning	Through study completion, an expected average of 2 years
Secondary	pruritus (All cohorts)	Using Visual Analog Scale (VAS) for prutitus assessment: From 0 = No pruritus to 10 = Pruritus as bad as it could possibly be	Through study completion, an expected average of 2 years
Secondary	ORR using blinded central review (Cohort 1)	Using the Olsen (2011, JCO) criteria	From the first dose until study completion, an expected average of 2 years
Secondary	Progression free survival (PFS) (All cohorts)		From the first dose until study completion, an expected average of 2 years
Secondary	Overall survival (OS) (All cohorts)		From the first dose until study completion, an expected average of 2 years
Secondary	PK parameters : Maximum Plasma Concentration of IPH4102 alone (All cohorts)	Maximum Plasma Concentration (Cmax) (W1, W5)	From the first dose until study completion, an expected average of 2 years
Secondary	PK parameters :Trough Concentration of IPH4102 alone (All cohorts)	Trough Concentration (Ctrough) every 8 or 12 weeks	From the first dose until study completion, an expected average of 2 years
Secondary	Immunogenicity of IPH4102 alone (All cohorts)	A serum sample will be collected at the specified time points for evaluation of anti-drug antibodies (ADA).	From the first dose until study completion, an expected average of 2 years
Secondary	Duration of Response (DOR)		From the first dose until study completion, an expected average of 2 years