Clinical Trials /

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

NCT03902184

Description:

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, and in patients with peripheral T-cell lymphoma in combination with gemcitabine and oxaliplatin chemotherapy (GEMOX)

Related Conditions:
  • Anaplastic Large Cell Lymphoma
  • Angioimmunoblastic T-Cell Lymphoma
  • Mycosis Fungoides
  • Peripheral T-Cell Lymphoma, Not Otherwise Specified
  • Sezary Syndrome
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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 Alone or in Combination With Chemotherapy in Patients With Advanced T-cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: IPH4102-201
  • SECONDARY ID: 2018-003969-33
  • NCT ID: NCT03902184

Conditions

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

Interventions

DrugSynonymsArms
IPH4102Cohort 1: Relapsed/refractory Sezary Syndrome
Gemcitabine + OxaliplatinGEMOXCohort 4: Peripheral T-cell lymphoma, KIR3DL2 expressing

Purpose

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, and in patients with peripheral T-cell lymphoma in combination with gemcitabine and oxaliplatin chemotherapy (GEMOX)

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: Relapsed/refractory Sezary SyndromeExperimentalIPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity.
  • IPH4102
Cohort 2: Stage IB-IV Mycosis Fungoides, KIR3DL2 expressingExperimentalIPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity.
  • IPH4102
Cohort 3: Stage IB-IV Mycosis Fungoides,KIR3DL2 non-expressingExperimentalIPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity.
  • IPH4102
Cohort 4: Peripheral T-cell lymphoma, KIR3DL2 expressingExperimentalIPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity. GEMOX will be administered every 2 weeks for a maximum of 8 cycles
  • IPH4102
  • Gemcitabine + Oxaliplatin
Cohort 5: Peripheral T-cell lymphoma, KIR3DL2 non-expressingExperimentalIPH4102 will be administered every week for 5 weeks then every 2 weeks for 10 administrations then every 4 weeks until disease progression or unacceptable toxicity. GEMOX will be administered every 2 weeks for a maximum of 8 cycles
  • IPH4102
  • Gemcitabine + Oxaliplatin

Eligibility Criteria

        Inclusion Criteria:

        - Cohort 1:

          1. Patients with relapsed/refractory Sezary Syndrome (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 Mycosis fongoïdes (MF);

          6. KIR3DL2 expression (Cohort 2) or non-expression (Cohort 3) by immunohistochemistry
             performed centrally on at least one 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 Peripheral T Cell Lymphoma (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) by immunohistochemistry
             performed centrally on at least one 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.

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:Using the Olsen (2011, JCO) criteria (Cohorts 1-3), or Lugano Criteria (Cohorts 4-5)

Secondary Outcome Measures

Measure:Incidence of Treatment-Emergent Adverse Events (Safety and tolerability)
Time Frame:From first dose until study completion, an expected average of 2 years
Safety Issue:
Description:patients with treatment-related adverse events as assessed by CTCAE v5.0
Measure:Quality of life (QoL) (Cohorts 1-3)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:Using the Skindex29 questionnaire to assesse the effects of skin disease on quality of life in three domains: Symptoms, Emotions, and Functioning
Measure:pruritus (Cohorts 1-3)
Time Frame:Through study completion, an expected average of 2 years
Safety Issue:
Description:Using Visual Analog Scale (VAS) for prutitus assessment: From 0 = No pruritus to 10 = Pruritus as bad as it could possibly be
Measure:ORR using central review (Cohort 1)
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:Using the Olsen (2011, JCO) criteria
Measure:ORR lasting at least 4 months (ORR4) (Cohorts 1-3)
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:Using the Olsen (2011, JCO) criteria
Measure:Progression free survival (PFS) (All cohorts)
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:
Measure:Overall survival (OS) (All cohorts)
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:
Measure:PK parameters : Maximum Plasma Concentration of IPH4102 alone (Cohorts1-3) or in combination with GEMOX (Cohorts 4 and 5);
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:Maximum Plasma Concentration (Cmax) (W1, W5)
Measure:PK parameters :Trough Concentration of IPH4102 alone (Cohorts1-3) or in combination with GEMOX (Cohorts 4 and 5);
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:Trough Concentration (Ctrough) every 8 or 12 weeks
Measure:Immunogenicity of IPH4102 alone (Cohorts1-3) or in combination with GEMOX (Cohorts 4 and 5);
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:A serum sample will be collected at the specified time points for evaluation of anti-drug antibodies (ADA).
Measure:The impact of treatment on minimal residual disease (MRD) (Cohort 1).
Time Frame:From the first dose until study completion, an expected average of 2 years
Safety Issue:
Description:A whole blood sample will be collected at the specified time points for evaluation of MRD

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Innate Pharma

Last Updated

September 30, 2019