Transplantation After Complete Response In Patients With T-cell Lymphoma

Not Applicable

Recruiting

• Conditions: Peripheral T Cell Lymphoma
• Interventions: Procedure: Chemotherapy + follow up; Procedure: Chemotherapy + ASCT + follow up

• Registration Number: NCT05444712
• Lead Sponsor: Hospices Civils de Lyon

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.

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2022-06-08
• Study First Submitted QC: 2022-06-29
• Study First Posted: 2022-07-06
• Study Start: 2022-08-01
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-26
• Last Update Posted: 2023-09-28
• Primary Completion: 2028-04-01
• Study Completion: 2028-04-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 204

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

Read More

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)

9. 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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy	Chemotherapy + follow up	The chemotherapy is one of the following regimen administrated every 3 weeks for 6 cycles according to local investigator's choice based on usual practices and European Medical Agency (EMA) approval : * "Cyclophosphamide, doxorubicin, Vincristine and prednisone": (CHOP) * "Cyclophosphamide, doxorubicin, vincristine, etoposide and prednisone": (CHOEP) * "Brentuximab vedotin, cyclophosphamide, doxorubicin, prednisone": (BV-CHP) for ALCL lymphoma only (based on EMA approval)
Chemotherapy + ASCT	Chemotherapy + ASCT + follow up	Chemotherapy administrated every 3 weeks for 6 cycles according to local investigator's choice based on usual practices: Patients with ASCT strategy in Complete Response after 6 cycles will receive a High Dose Therapy (HDT) composed of BCNU, etoposide, cytarabine and melphalan (BEAM) as conditioning regimen before transplantation. That consolidation phase will lasts between 2 to 3 months

Primary Outcome Measures

Name	Time	Method
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	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	progression-free survival defined time from the date of randomization to the date of first documentation of relapse or progressive disease, death due to any cause, or receipt of subsequent systemic chemotherapy to treat residual or progressive peripheral T-cell lymphoma as determined by the investigator, whichever came first.

Secondary Outcome Measures

Name	Time	Method
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of duration of Response (DoR)	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	Duration of response will be measured from the time of attainment of CMR or PMR to the date of first documented disease progression, relapse (based on investigator disease assessment), death from any cause or receipt of subsequent systemic chemotherapy to treat residual or progressive peripheral T-cell lymphoma as determined by the investigator, whichever came first.
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of time to next Treatment (TTNT)	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	TTNT will be measured from the date of randomization to the date of first documented administration of new anti-lymphoma treatment.
To Evaluate PET-CT Omics	at patient enrollment	PET-Omics
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	After four cycles of chemotherapy (each cycle is 3weeks)	Predictive value of an early PET_CT after 4 cycles of chemotherapy on treatment response according to the IWC Lugano 2014
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of budget Impact Analysis	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	budget impact analysis to assess the potential annual economic impact of the new management recommendation (with or without ASCL) for the French Public Health Insurance System across a 3-year time period.
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of Overall response rate (ORR) and Complete Response Rate (CRR)	At the end of ASCT (8-12 weeks after post-induction evaluation)	Overall Response Rate is defined as the proportion of subjects achieving best overall response of partial metabolic response (PMR) or complete metabolic response (CMR) at the end of ASCT (8-12 weeks after PIE). Assessment of response will be determined by investigator and based on Lugano Response Criteria 2014 (PET-CT-Based Response for FDG-avid lymphomas or CT-Based Response if not).
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of quality of Life	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	The EuroQol 5 Dimensions questionnaire (EQ5D-5L) will be administered at baseline and every three months during follow-up visit.
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of cost-Effectiveness Analysis	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	Will be expressed as the extra cost per a quality adjusted life year. To assess the mean cost per patient of each group, the number of resources consumed and the amounts refunded will be extracted from the French National Health Insurance Information System. The number of QALYs in each group of the trial will be assessed with survival time and the validated EuroQol 5 Dimensions questionnaire (EQ5D-5L).
Adjusted comparison of chemotherapy regimens (CHOP vs CHOEP) in non-sALCL in terms of Overall Response Rate (ORR)	at the end of induction (between 3 and 5 weeks after the last drug administration)	Overall Response Rate is defined as the proportion of subjects achieving best overall response of partial metabolic response (PMR) at the end of induction. Assessment of response will be determined by investigator and based on Lugano Response Criteria 2014 (PET-CT-Based Response for FDG-avid lymphomas or CT-Based Response if not).
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of Overall survival (OS)	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	Overall survival will be measured from the date of randomization to the date of death from any cause
Adjusted comparison of chemotherapy regimens (CHOP vs CHOEP) in non-sALCL in terms of Complete Response rate (CRR)	at the end of induction (between 3 and 5 weeks after the last drug administration)	complete metabolic response is defined as the proportion of subjects achieving complete metabolic response (CMR) at the end of induction. Assessment of response will be determined by investigator and based on Lugano Response Criteria 2014 (PET-CT-Based Response for FDG-avid lymphomas or CT-Based Response if not).
To evaluate the predictive value of total metabolic tumor volume (TMTV) on PET-CT	at patient enrollment	Predictive value of TMTV on PET-CT

Trial Locations

Locations (48)

Ch de Dunkerque; 🇫🇷 Dunkerque, France

Centre Leon Berard; 🇫🇷 Lyon, France

Ch de Roubaix - Hopital Victor Provo; 🇫🇷 Roubaix, France

Centre Henri Becquerel; 🇫🇷 Rouen, France

Chu de La Reunion - Hopital Felix Guyon; 🇫🇷 Saint-Denis, France

Chu de Montpellier; 🇫🇷 Montpellier, France

Chu D'Angers; 🇫🇷 Angers, France

Ch Victor Dupouy; 🇫🇷 Argenteuil, France

Chu D'Amiens - Hopital Sud; 🇫🇷 Amiens, France

Ch D'Avignon - Hopital Henri Duffaut; 🇫🇷 Avignon, France

Service d'Onco-radiolothérapie, Polyclinique Bordeaux Nord Aquitaine; 🇫🇷 Bordeaux, France

Ch de La Cote Basque; 🇫🇷 Bayonne, France

Ch Metropole Savoie - Site Chambery; 🇫🇷 Chambéry, France

Ch Alpes Leman; 🇫🇷 Contamine sur Arve, France

Hopital Henri Mondor; 🇫🇷 Creteil, France

Chu Estaing; 🇫🇷 Clermont-Ferrand, France

René Olivier Casasnovas; 🇫🇷 Dijon, France

Chd de Vendee; 🇫🇷 La Roche-sur-Yon, France

CHU Francois MITTERRAND; 🇫🇷 Dijon, France

Ch de Versailles - Hopital Andre Mignot; 🇫🇷 Le Chesnay, France

CHU du Mans; 🇫🇷 Le Mans, France

Service Oncologie médicale, HOPITAL SAINT VINCENT-DE-PAUL; 🇫🇷 Lille, France

Service Hématologie Clinique et Thérapie Cellulaire, CHU DE LIMOGES - HOPITAL DUPUYTREN,; 🇫🇷 Limoges, France

Centre Antoine Lacassagne; 🇫🇷 Nice, France

Chu de Nantes; 🇫🇷 Nantes, France

Chu de Nimes - Hopital Caremeau; 🇫🇷 Nîmes, France

Hopital Cochin; 🇫🇷 Paris, France

Chr Orleans; 🇫🇷 Orléans, France

Hopital de La Pitie Salpetriere; 🇫🇷 Paris, France

Hopital Necker; 🇫🇷 Paris, France

Ch de Perpignan; 🇫🇷 Perpignan, France

Chu de Bordeaux - Hopital Haut-Leveque; 🇫🇷 Pessac, France

Hopital Saint Antoine; 🇫🇷 Paris, France

Ch Annecy Genevois; 🇫🇷 Pringy, France

Ch Perigueux; 🇫🇷 Périgueux, France

Chu Lyon-Sud; 🇫🇷 Pierre Benite, France

Chu Pontchaillou_Rennes; 🇫🇷 Rennes, France

Chu de La Reunion - Ghsr; 🇫🇷 Saint-Pierre, France

Institut Cancerologie & Hematologie St-Etienne; 🇫🇷 Saint-Priest-en-Jarez, France

Service Hématologie, Institut Curie - Hôpital René HUGUENIN; 🇫🇷 Saint-Cloud, France

Ch de Saint-Quentin; 🇫🇷 Saint-Quentin, France

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, France

Institut Universitaire du Cancer; 🇫🇷 Toulouse, France

Chu Bretonneau; 🇫🇷 Tours, France

Ch de Valenciennes - Hopital Jean Bernard; 🇫🇷 Valenciennes, France

Ch de Valence; 🇫🇷 Valence, France

Chu Brabois; 🇫🇷 Vandœuvre-lès-Nancy, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France