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JOURNAL ONKOLOGIE – STUDIE

Study of Lacutamab in Peripheral T-cell Lymphoma

Rekrutierend

NCT-Nummer:
NCT04984837

Studienbeginn:
Oktober 2021

Letztes Update:
05.12.2023

Wirkstoff:
Lacutamab, Gemcitabine, Oxaliplatine

Indikation (Clinical Trials):
Lymphoma, Lymphoma, T-Cell, Lymphoma, T-Cell, Peripheral, Recurrence

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
The Lymphoma Academic Research Organisation

Collaborator:
Innate Pharma

Studienleiter

Morgane Cheminant
Study Chair
Lymphoma Study Association

Kontakt

Studienlocations
(3 von 64)

Charite Universitat Smedizin Berlin
Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Universitatsklinikum Halle (Saale)
Halle
(Sachsen-Anhalt)
GermanyRekrutierend» Google-Maps
UNIVERSITAT LEIPZIG - Klinik fur Hamatologie, Zelltherapie und Hamostaseo
Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps
UNIVERSITATSKLINIKUM REGENSBURG - Klinik für Innere Medizin III
Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps
Cliniques Universitaires de Bruxelles - Hôpital Erasme
Bruxelles
BelgiumSchwebend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief Summary:

This is an open-label multicenter randomized non comparative phase II study to evaluate the

safety and efficacy of the monoclonal anti-KIR3DL2 antibody Lacutamab in patients with

Refractory/Relapsing (R/R) KIR3DL2 positive Peripheral T Cell Lymphoma (PTCL) : Not Other

Specified (NOS), PTCL-TFH (including Angioimmunoblastic T-cell Lymphoma (AITL), Follicular

T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype), Anaplastic large cell

lymphoma (ALCL), Adult T-cell leukemia/lymphoma (ATL), Hepatosplenic T-cell lymphoma (HSTL),

Enteropathy-associated T-cell lymphoma (EATL), Monomorphic epitheliotropic intestinal T cell

lymphoma (MEITL), NK-T cell lymphoma (NKT) and Aggressive NK-cell leukemia (ANKL).

The design is non comparative meaning that non comparison between arms will be performed as

the control arm will ensure that the assumptions used for sample size calculation are

verified. For that reason, randomization is unbalanced in favor of the experimental arm

(2:1).

Ein-/Ausschlusskriterien

Inclusion Criteria:

- 1. KIR3DL2-positive with at least 1% of tumour cells positivity, before randomization,

based on central evaluation by immunohistochemistry (IHC) 2. Patients with

histologically documented PTCL:

- Biopsy-proven treated PTCL defined by the WHO 2016 criteria (the biopsy at

relapse is recommended but not mandatory):

- PTCL-NOS

- PTCL-TFH (AITL, Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma

with TFH phenotype)

- ALCL

- ATL: acute- or lymphoma-type

- HSTL

- EATL

- MEITL

- NKT

- ANKL 3. For patients with ALCL: previously treated with brentuximab vedotin

4. Relapsed/refractory PTCL after at least one previous line of systemic

based regimen of chemotherapy (no mandatory latency after the previous

treatment) 5. With a maximum of 2 prior lines of systemic therapies,

including autologous stem cell transplantation (ASCT is authorized in first

and second line and is not counted as a unique line, even if associated to a

systemic therapy) 6. Bi-dimensionally measurable disease defined by at least

one single node or tumor lesion ≥ 1.5 cm assessed by CT scan 7. Signed

written screening informed consent prior to KIR3DL2 screening 8. Signed

written study informed consent prior to randomization 9. Aged 18 years or

more with no upper age limit, at randomization 10. Eastern Cooperative

Oncology Group (ECOG) performance status 0 to 3 prior to prephase treatment

(if applicable), and 0 to 2 prior randomization 11. Minimum life expectancy

of 3 months 12. Females of childbearing potential (FCBP) must agree to use

highly effective contraceptive method* from C1D1, during the entire study

period, during dose interruptions, and for 9 months after the last study

treatments 13. FCBP must have a negative serum or urinary pregnancy test

within 28 days prior C1D1 14. Male patients and their partner (FCBP) must

agree to use two reliable forms of contraception (condom for males and

hormonal method for partners) from C1D1, during the entire study period,

during dose interruptions, and for 9 months after the last study treatments

Exclusion Criteria:

- 1. Patients with active COVID-19 infection (last positive PCR < 2 weeks before

randomization) 2. Patients taking immunotherapy or chemotherapy, except short-term

corticosteroids in monotherapy at a cumulated dose equivalent of prednisone ≤

1mg/kg/day, during 7 consecutive days, within 3 weeks prior to first administration of

study drug (C1D1); or prephase treatment given at investigator's discretion before

randomization and for maximum 3 weeks (glucocorticosteroids, vepesid (VP16),

cyclophosphamide, vincristine and prednisone (COP)) 3. Previous treatment by

Gemcitabine or Oxaliplatin 4. Use of any experimental anti-cancer drug therapy within

6 weeks before randomization 5. Contraindication to any drug contained in the study

treatment regimen 6. Previous allogenic hematopoietic cell transplantation 7. Positive

test results for HIV and Hepatitis C Virus (HCV) (Patients who are positive for HCV

antibody must be negative for HCV by PCR to be eligible for study participation) 8.

Known active hepatitis B (positive Ag HBs) (if latent Hepatitis B Virus (HBV)

(positive anti-HBc), patients have to be treated with Entecavir (Baraclude ®) and HBV

PCR should be performed every month to allow antiviral strategy adaptation) 9. Central

nervous system or meningeal involvement by lymphoma 10. Any of the following

laboratory abnormalities prior randomization:

- Absolute neutrophil count (ANC) < 1 G/L, unless neutropenia is related to PTCL

- Platelet count < 75 G/L, unless thrombopenia is related to PTCL

- Alkaline Phosphatases > 2.5 x upper limit of normal (ULN)

- Serum Glutamoyl-oxaloacetate Transferase (SGOT) /Alanine aminotransferase (AST)

or Serum Glutamate Pyruvate Transaminase (SGPT)/Alanine aminotransferase (ALT) >

2.5 x ULN

- Bilirubin > 1.5 x ULN, unless SGOT/AST and SGPT/ALT > 2.5 x ULN or bilirubin

elevated due to PTCL or hemolysis

- Calculated creatinine clearance (MDRD or Cockcroft) < 40 mL/min 11. Any

significant cardiovascular impairment: New York Heart Association (NYHA) Class

III or IV cardiac disease, uncontrolled high blood pressure, unstable angina,

myocardial infarction or stroke within the last 6 months from randomization, and

cardiac arrhythmia within the last 3 months from randomization 12. Uncontrolled

clinically significant intercurrent illness including, but not limited to,

diabetes, ongoing active infections. Patients receiving antibiotics for

infections that are under control may be included in the study 13. Concurrent

malignancy or prior history of malignancies other than lymphoma unless the

subject has been free of disease for ≥ 2 years, except early stage cutaneous

squamous or basal cell carcinoma, localized prostate cancer, or cervical

intraepithelial neoplasia 14. Major surgery within 4 weeks before randomization

15. Pregnant or lactating females

Studien-Rationale

Primary outcome:

1. median modified progression-free survival (mPFS) - CT-based (Time Frame - 5,5 years.):
time from randomization until one of the following events occurs, whichever comes first: Disease progression (PD) Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)) Relapse after achievement of CR Death due to any cause. PD and relapse will be evaluated according to Lugano 2014 criteria (CT-based).



Secondary outcome:

1. median modified progression-free survival (mPFS) - PET-based (Time Frame - 5,5 years.)

2. Number of Adverse Events (Time Frame - 5,5 years.)

3. overall survival (OS) (Time Frame - 5,5 years.)

4. complete response rate (CRR) Lugano 2014 criteria (CT-based) (Time Frame - 5,5 years.)

5. complete response rate (CRR) Lugano 2014 criteria (PET-based) (Time Frame - 5,5 years.)

6. overall response rate (ORR) Lugano 2014 criteria (CT-based) (Time Frame - 5,5 years.)

7. overall response rate (ORR) Lugano 2014 criteria (PET-based) (Time Frame - 5,5 years.)

8. response rate assessed by Deauville criteria (Time Frame - 5,5 years.)

9. duration of response (DOR), (Time Frame - 5,5 years.):
Disease progression (PD) Administration of any additional unplanned anti-lymphoma treatment (except allogeneic or autologous hematopoietic cell transplantations (HCT)) Relapse after achievement of CR Death due to any cause

10. rate of patients proceeding to allogenic stem cell transplantation (Time Frame - 5,5 years.)

11. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 1 month (1 cycle))

12. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 1 month (1 cycle))

13. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 2 months (2 cycles))

14. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 2 months (2 cycles))

15. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 3 months (3 cycles))

16. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 3 months (3 cycles))

17. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 7 months (7 cycles))

18. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 7 months (7 cycles))

19. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 9 months (9 cycles))

20. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 9 months (9 cycles))

21. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 15 months (15 cycles))

22. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 15 months (15 cycles))

23. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 26 months (26 cycles))

24. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 26 months (26 cycles))

25. Pharmacokinetics of lacutamab with GemOx : Maximal Concentration of lacutamab (Cmax) (Time Frame - 29 months (29 cycles))

26. Pharmacokinetics of lacutamab with GemOx : Trough Concentration of lacutamab (Ctrough) (Time Frame - 29 months (29 cycles))

27. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 1 month (1 cycle))

28. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 2 months (2 cycles))

29. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 3 months (3 cycles))

30. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 7 months (7 cycles))

31. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 9 months (9 cycles))

32. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 15 months (15 cycles))

33. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 26 months)

34. Immunogenicity : concentration of Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (Time Frame - 29 months)

Studien-Arme

  • Experimental: Lacutamab
    Lacutamab 750 mg/IV + GEmOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase Lacutamab 750 mg/IV for a maximum of 20 additional cycles of 4 weeks during the maintenance phase
  • Active Comparator: Standard of care
    GemOx (1000 mg/m² / 100 mg/m²) 6 cycles of 3 weeks (4,5 months) during the induction phase

Geprüfte Regime

  • Lacutamab:
    750 mg/IV
  • Gemcitabine:
    1000 mg/m²
  • Oxaliplatine:
    100 mg/m²

Quelle: ClinicalTrials.gov


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