E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Relapsed/refractory PTCL KIR3DL2-positive patients after at least one previous line of systemic based regimen of chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
Relapsed/refractory patients with peripheral T-cell lymphoma |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042980 |
E.1.2 | Term | T-cell lymphoma refractory |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042979 |
E.1.2 | Term | T-cell lymphoma recurrent |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the median modified progression-free survival (mPFS) of Lacutamab in patients treated with Gemcitabine-oxaliplatin (GemOx) at relapse followed by a Lacutamab maintenance, in relapsed/refractory (R/R) patients with KIR3DL2 positive PTCL-NOS, PTCL-T Follicular Helper (TFH) (including AITL, Follicular T-cell lymphoma, Nodal peripheral T-cell lymphoma with TFH phenotype), ALCL, ATL, HSTL, enteropathy-associated Tcell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), NK T-cell lymphoma (NKT) and aggressive NK-cell leukemia (ANKL).
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E.2.2 | Secondary objectives of the trial |
- To characterize the safety and tolerability of Lacutamab (on both arms) - To evaluate overall survival (OS) - To evaluated mPFS with PD and relapse evaluated according to Lugano 2014 criteria (PET-based) - To evaluate other clinical activity endpoints: 1. complete response (CR) rate and overall response rate (ORR) according to Lugano 2014 criteria (CTscan) 2. CR rate and ORR according to Lugano 2014 criteria (PET scan) during induction 3. response rate assessed by Deauville criteria 4. duration of response (DOR), calculated as time from first CR or PR according to Lugano 2014 criteria (CT-based) until one of the following events occurs, whichever comes first: -To characterize the Pharmacokinetics of lacutamab with GemOx (for experimental arm only) - To evaluate the immunogenicity (Anti-Drug Antibodies (ADA)) of lacutamab with GemOx (for experimental arm only) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. KIR3DL2-positive with at least 1% of tumour cells positivity, before randomization, based on central evaluation by IHC 2. Patients with histologically documented PTCL 3. Relapsed/refractory PTCL after at least one previous line of systemic based regimen of chemotherapy (no mandatory latency after the previous treatment) 4. With a maximum of 2 prior lines of systemic therapies, including autologous stem cell transplantation 5. Bi-dimensionally measurable disease defined by at least one single node or tumor lesion ≥ 1.5 cm assessed by CT scan 6. Signed written screening informed consent prior to KIR3DL2 screening 7. Signed written study informed consent prior to randomization 8. Aged 18 years or more with no upper age limit, at randomization 9. ECOG performance status 0 to 3 prior to prephase treatment (if applicable), and 0 to 2 prior randomization 10. Minimum life expectancy of 3 months 11. 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 12. FCBP must have a negative serum or urinary pregnancy test within 28 days prior C1D1 13. 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 |
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E.4 | Principal 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, vepeside (VP16), cyclophosphamide, vincristine and prednisone ≤ 1mg/kg/day (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. Positive test results for HIV and HCV 7. Known active hepatitis B (positive Ag HBs) 8. Central nervous system or meningeal involvement by lymphoma 9. Any of the following laboratory abnormalities prior randomization: o Absolute neutrophil count (ANC) < 1 G/L, unless neutropenia is related to PTCL o Platelet count < 75 G/L, unless thrombopenia is related to PTCL o Alkaline Phosphatases > 2.5 x upper limit of normal (ULN) o Serum SGOT/AST or SGPT/ALT > 2.5 x ULN o Bilirubin > 1.5 x ULN, unless SGOT/AST and SGPT/ALT > 2.5 x ULN or bilirubin elevated due to PTCL or hemolysis o Calculated creatinine clearance (MDRD or Cockroft) < 40 mL/min 10. Any significant cardiovascular impairment: 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 11. 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 12. 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 13. Major surgery within 4 weeks before randomization 14. Pregnant or lactating females
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E.5 End points |
E.5.1 | Primary end point(s) |
median modified progression-free survival (mPFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
6.5 months after the randomization of the last patient or at the latest when median modified PFS has been reached in the experimental arm. |
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E.5.2 | Secondary end point(s) |
- safety and tolerability of Lacutamab - overall survival (OS) - mPFS to Lugano 2014 criteria (PET-based) - complete response (CR) rate - overall response rate (ORR) according to Lugano 2014 criteria (CTscan) - CR rate and ORR according to Lugano 2014 criteria (PET scan) during induction - response rate assessed by Deauville criteria - duration of response (DOR) - Pharmacokinetics of lacutamab with GemOx - immunogenicity (Anti-Drug Antibodies (ADA)) of lacutamab with GemOx |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
- safety and tolerability of Lacutamab = 28 days after the end of treatment - overall survival (OS) = end of study - mPFS to Lugano 2014 criteria (PET-based) = 6.5 months after the randomization of the last patient - complete response (CR) rate = 3 cycles and end of induction - overall response rate (ORR) = 3 cycles and end of induction - response rate assessed = 3 cycles and end of induction - duration of response (DOR) = end of study - Pharmacokinetics and immunogenicity lacutamab with GemOx : C1, C2, C3, C7, C9, C15, end of treatment, M3 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 31 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of study will occur when all patients have been followed-up for survival for at least 6 months after their End of treatment/observation evaluation, have died, have withdrawn their consent, or are lost to follow up (whatever the event that occurs first). |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 6 |