Clinical trial NCT05444712: Transplantation After Complete Response In Patients With T-cell Lymphoma
Official title: Transplantation After Complete Response In Patients With T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Peripheral T Cell Lymphoma
Keywords: peripheral T-cell Lymphoma
autologous stem cell transplantation
chemotherapy
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2022-07-06
Enrollment: 204
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Peripheral T-cell lymphoma (PTCL) encompasses a broad range of post-thymic (i.e., mature) sub-entities as defined by the 2017 WHO classification. The most common entities are angioimmunoblastic T-cell lymphoma (AITL) and other Tfh-phenotype PTCL or PTCL not otherwise specified (NOS), each representing approximately 20 to 25% of mature T- and NK/T-cell lymphomas. Compared to their B-cell counterparts, most PTCL confer dismal prognosis. In fact, except for anaplastic lymphoma kinase (ALK)-positive systemic anaplastic large cell lymphoma (sALCL), 10-year overall survival for patients with PTCL barely exceeds 30%. Given the infrequency and the heterogeneity of these malignancies, no real consensus on first-line treatment has been established for most PTCL.

The place of autologous stem cell transplantation (ASCT) as a consolidation procedure for patients with PTCL achieving a complete metabolic response after induction is still highly debated. ESMO recommendations and recent guidelines from a committee of the American Society for Blood and Marrow Transplantation currently propose ASCT as first-line therapy for transplant-eligible patients for all patients reaching at least a partial response (PR) after induction. NCCN guidelines (version 2.2017) recommend ASCT or observation in case of metabolic CR but salvage regimen in case of residual disease after induction.


Eligibility criteria: Inclusion Criteria:

1. Patient ≥ 18 years and \< 70 years of age at the time of signing the informed consent form (ICF)
2. Patient fit enough to receive autologous stem cell transplant as a consolidation strategy as assessed by the local investigator
3. Hemoglobin level \> 8g/dL (transfusion allowed); Neutrophil count \>0.5 G/L; Platelets count \> 50 G/L (transfusion allowed) Patient with histologically proven "nodal-type peripheral T-cell lymphoma (PTCL)" (latest WHO classification), not previously treated; as defined by the WHO classification, the following subtypes may be included,

   * PTCL, not otherwise specified
   * Follicular helper T-cell lymphomas: Angioimmunoblastic T-cell lymphoma and nodal PTCL with TFH phenotype and follicular T-cell lymphoma
   * Anaplastic large cell lymphoma, ALK-negative
4. Ann Arbor staging (I-IV) except stage I with normal LDH and PS\<2 (i.e. stage I aaIPI 0)
5. Participant with a measurable disease by the Lugano criteria (i.e., longest diameter of a nodal site \> 1.5 cm and/or longest diameter of an extranodal site \> 1.0 cm and/or a hypermetabolic lesion)
6. FFPE Diagnostic tissue block should be available for central pathology review and ancillary molecular analyses
7. Participant with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
8. Estimated minimum life expectancy of 3 months
9. Patient who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted
10. Able to adhere to the study visit schedule and other protocol requirements
11. Patient covered by any social security system (France)
12. Patient who understands and speaks one of the country official languages
13. Males with partners of childbearing potential must agree to use effective birth control methods during the study as informed by the investigator in accordance with SmPC of each drugs administrated
14. Females of childbearing potential must agree to use effective birth control methods for at least 28 days before starting treatment; while participating in the study; during treatment interruptions and necessary period after the study as informed by the investigator in accordance with SmPC of each drugs administrated

Exclusion Criteria:

1. Known central nervous system or meningeal involvement by lymphoma
2. Impaired renal function (calculated MDRD or Cockcroft-Gault Creatinine Clearance \< 30 ml/min) or impaired liver function tests (serum total bilirubin level \> 2.0 mg/dl \[34 µmol/L\] (except in case of Gilbert's Syndrome, or documented liver or pancreatic involvement by lymphoma), serum transaminases (AST or ALT) \> 3 upper normal limit unless they are related to the lymphoma.
3. The following types of T-cell lymphomas:

   * Adult T-cell lymphoma/leukemia (HTLV-1 related T-cell lymphoma)
   * Extranodal T-cell/NK-cell lymphoma, nasal type
   * Anaplastic large cell lymphoma, ALK-positive type
   * Cutaneous T cell lymphoma (mycosis fungoides, Sézary syndrome)
   * Primary cutaneous CD30+ T-cell lymphoproliferative disorder
   * Primary cutaneous anaplastic T-cell lymphoma
   * Enteropathy-associated T-cell lymphoma
   * Hepatosplenic T-cell lymphoma
   * Subcutaneous panniculitis-like T-cell lymphoma
   * Primary cutaneous gamma-delta T-cell lymphoma
   * Primary cutaneous CD8+ aggressive epidermotropic lymphoma
   * Primary cutaneous CD4+ small/medium T-cell lymphoma
4. Active malignancy other than the one treated in this research. Prior history of malignancies unless the patient has been free of the disease for ≥ 2 years. However, patients with the following history are allowed:

   1. Basal or squamous cell carcinoma of the skin
   2. Carcinoma in situ of the cervix
   3. Carcinoma in situ of the breast
   4. Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis clinical staging system
5. Vaccinated with live, attenuated vaccines within 6 months of enrollment
6. Use of any standard or experimental anti-cancer drug therapy before the start of treatment except COP (cyclophosphamide, vincristine, prednisone) in case of (or high risk of tumor lysis syndrome) or etoposide for a maximum of 3 doses (at a maximum dose of 150mg/m2) for HLH (Hemophagocytic Lymphohistiocytosis).
7. A corticosteroids therapy \> 1mg/kg lasting more than 14 days prior to Cycle 1 Day 1
8. Positive serology for Human Immunodeficiency Virus (HIV) and Human T-Lymphotrophic Virus (HTLV1)

15. Active Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) infections defined as:

* HBV :
* HBs Ag positive
* HBs Ag negative, anti-HBs antibody positive and anti-HBc antibody positive with detectable viral DNA
* HCV :

Anti-VHC antibody positive with detectable viral RNA 9. Pregnant, planning to become pregnant or lactating WOCBP 10. Any significant medical conditions, laboratory abnormality or psychiatric illness likely to interfere with the participation in this clinical study (according to the investigator's decision) 11. Person deprived of his/her liberty by a judicial or administrative decision 12. Person hospitalized without consent 13. Adult person under legal protection

Primary outcomes:
measure: to assess if ASCT is associated with a significant prolongation of progression-free survival (PFS) for patient with peripheral T-cell lymphoma (PTCL) reaching a complete response (CR) according to the response critter
timeFrame: When the last randomized patient has reached two years of follow-up or when 154 events (progression/relapse/new anti-lymphoma treatment/death) occured whichever comes first
Secondary outcomes:
measure: Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of Overall survival (OS)
timeFrame: When the last randomized patient has reached two years of follow-up or when 154 events (progression/relapse/new anti-lymphoma treatment/death) occured whichever comes first
measure: Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of Overall response rate (ORR) and Complete Response Rate (CRR)
timeFrame: At the end of ASCT (8-12 weeks after post-induction evaluation)
measure: Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of duration of Response (DoR)
timeFrame: When the last randomized patient has reached two years of follow-up or when 154 events (progression/relapse/new anti-lymphoma treatment/death) occured whichever comes first
measure: Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of time to next Treatment (TTNT)
timeFrame: When the last randomized patient has reached two years of follow-up or when 154 events (progression/relapse/new anti-lymphoma treatment/death) occured whichever comes first
measure: Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of quality of Life
timeFrame: When the last randomized patient has reached two years of follow-up or when 154 events (progression/relapse/new anti-lymphoma treatment/death) occured whichever comes first
measure: Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of cost-Effectiveness Analysis
timeFrame: When the last randomized patient has reached two years of follow-up or when 154 events (progression/relapse/new anti-lymphoma treatment/death) occured whichever comes first
measure: Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of budget Impact Analysis
timeFrame: When the last randomized patient has reached two years of follow-up or when 154 events (progression/relapse/new anti-lymphoma treatment/death) occured whichever comes first
measure: Adjusted comparison of chemotherapy regimens (CHOP vs CHOEP) in non-sALCL in terms of Overall Response Rate (ORR)
timeFrame: at the end of induction (between 3 and 5 weeks after the last drug administration)
measure: Adjusted comparison of chemotherapy regimens (CHOP vs CHOEP) in non-sALCL in terms of Complete Response rate (CRR)
timeFrame: at the end of induction (between 3 and 5 weeks after the last drug administration)
measure: To evaluate the predictive value of total metabolic tumor volume (TMTV) on PET-CT
timeFrame: at patient enrollment
measure: To Evaluate PET-CT Omics
timeFrame: at patient enrollment
measure: The assessment of the early PET-CT predictive value after four cycles of chemotherapy on treatment response according to the IWC (International Workshop Criteria) Lugano 2014
timeFrame: After four cycles of chemotherapy (each cycle is 3weeks)
Other outcomes:
Locations:
city: Amiens
country: France
facility: Chu D'Amiens - Hopital Sud
city: Angers
country: France
facility: Chu D'Angers
city: Argenteuil
country: France
facility: Ch Victor Dupouy
city: Avignon
country: France
facility: Ch D'Avignon - Hopital Henri Duffaut
city: Bayonne
country: France
facility: Ch de La Cote Basque
city: Bordeaux
country: France
facility: Service d'Onco-radiolothérapie, Polyclinique Bordeaux Nord Aquitaine
city: Chambéry
country: France
facility: Ch Metropole Savoie - Site Chambery
city: Clermont-Ferrand
country: France
facility: Chu Estaing
city: Contamine sur Arve
country: France
facility: Ch Alpes Leman
city: Creteil
country: France
facility: Hopital Henri Mondor
city: Dijon
country: France
facility: René Olivier Casasnovas
city: Dijon
country: France
facility: CHU Francois MITTERRAND
city: Dunkerque
country: France
facility: Ch de Dunkerque
city: La Roche-sur-Yon
country: France
facility: Chd de Vendee
city: Le Chesnay
country: France
facility: Ch de Versailles - Hopital Andre Mignot
city: Le Mans
country: France
facility: CHU du Mans
city: Lille
country: France
facility: Service Oncologie médicale, HOPITAL SAINT VINCENT-DE-PAUL
city: Limoges
country: France
facility: Service Hématologie Clinique et Thérapie Cellulaire, CHU DE LIMOGES - HOPITAL DUPUYTREN,
city: Lyon
country: France
facility: Centre Leon Berard
city: Montpellier
country: France
facility: Chu de Montpellier
city: Nantes
country: France
facility: Chu de Nantes
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Nîmes
country: France
facility: Chu de Nimes - Hopital Caremeau
city: Orléans
country: France
facility: Chr Orleans
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital de La Pitie Salpetriere
city: Paris
country: France
facility: Hopital Necker
city: Paris
country: France
facility: Hopital Saint Antoine
city: Perpignan
country: France
facility: Ch de Perpignan
city: Pessac
country: France
facility: Chu de Bordeaux - Hopital Haut-Leveque
city: Pierre Benite
country: France
facility: Chu Lyon-Sud
city: Pringy
country: France
facility: Ch Annecy Genevois
city: Périgueux
country: France
facility: Ch Perigueux
city: Rennes
country: France
facility: Chu Pontchaillou_Rennes
city: Roubaix
country: France
facility: Ch de Roubaix - Hopital Victor Provo
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint-Cloud
country: France
facility: Service Hématologie, Institut Curie - Hôpital René HUGUENIN
city: Saint-Denis
country: France
facility: Chu de La Reunion - Hopital Felix Guyon
city: Saint-Pierre
country: France
facility: Chu de La Reunion - Ghsr
city: Saint-Priest-en-Jarez
country: France
facility: Institut Cancerologie & Hematologie St-Etienne
city: Saint-Quentin
country: France
facility: Ch de Saint-Quentin
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
city: Toulouse
country: France
facility: Institut Universitaire du Cancer
city: Tours
country: France
facility: Chu Bretonneau
city: Valence
country: France
facility: Ch de Valence
city: Valenciennes
country: France
facility: Ch de Valenciennes - Hopital Jean Bernard
city: Vandœuvre-lès-Nancy
country: France
facility: Chu Brabois
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: HCL
name: Emmanuel BACHY, Pr
role: PRINCIPAL_INVESTIGATOR
References: