TRANSCRIPT: Transplantation After Complete Response In Patients With T-cell Lymphoma

Sponsor

Hospices Civils de Lyon (Other)

Overall Status

Recruiting

CT.gov ID

NCT05444712

Collaborator

(none)

204

Enrollment

Locations

Arms

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral T Cell Lymphoma	Procedure: Chemotherapy + follow up Procedure: Chemotherapy + ASCT + follow up	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

204 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Health Services Research

Official Title:

Transplantation After Complete Response In Patients With T-cell Lymphoma

Actual Study Start Date :

Aug 1, 2022

Anticipated Primary Completion Date :

Apr 1, 2028

Anticipated Study Completion Date :

Apr 1, 2028

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Chemotherapy 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)	Procedure: Chemotherapy + follow up Chemotherapy administrated every 3 weeks for 6 cycles according to local investigator's choice based on usual practices. An intermediate evaluation will be performed after four cycles by PET-CT (or CT-Scan for non-avid PTCL) A post-induction evaluation by PET-CT or CT-Scan will be done between 3 and 5 weeks after the last chemotherapy drug administration for all patients A last evaluation by PET-CT or CT-Scan will be done between 08 and 12 weeks after the post-induction for all patients
Active Comparator: Chemotherapy + ASCT 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	Procedure: Chemotherapy + ASCT + follow up Chemotherapy administrated every 3 weeks for 6 cycles according to local investigator's choice based on usual practices. An intermediate evaluation will be performed after four cycles by PET-CT (or CT-Scan for non-avid PTCL) The fifth or sixth cycles should be used as stem-cell mobilizing chemotherapy for patients with ASCT strategy A post-induction evaluation by PET-CT or CT-Scan will be done between 3 and 5 weeks after the last chemotherapy drug administration for all patients Patients with in Complete Response after 6 cycles will receive a High Dose Therapy as conditioning regimen before transplantation A last evaluation by PET-CT or CT-Scan will be done between 08 and 12 weeks after the post-induction for all patients

Arm

Intervention/Treatment

Active Comparator: Chemotherapy

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)

Procedure: Chemotherapy + follow up

Chemotherapy administrated every 3 weeks for 6 cycles according to local investigator's choice based on usual practices. An intermediate evaluation will be performed after four cycles by PET-CT (or CT-Scan for non-avid PTCL) A post-induction evaluation by PET-CT or CT-Scan will be done between 3 and 5 weeks after the last chemotherapy drug administration for all patients A last evaluation by PET-CT or CT-Scan will be done between 08 and 12 weeks after the post-induction for all patients

Active Comparator: Chemotherapy + ASCT

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

Procedure: Chemotherapy + ASCT + follow up

Chemotherapy administrated every 3 weeks for 6 cycles according to local investigator's choice based on usual practices. An intermediate evaluation will be performed after four cycles by PET-CT (or CT-Scan for non-avid PTCL) The fifth or sixth cycles should be used as stem-cell mobilizing chemotherapy for patients with ASCT strategy A post-induction evaluation by PET-CT or CT-Scan will be done between 3 and 5 weeks after the last chemotherapy drug administration for all patients Patients with in Complete Response after 6 cycles will receive a High Dose Therapy as conditioning regimen before transplantation A last evaluation by PET-CT or CT-Scan will be done between 08 and 12 weeks after the post-induction for all patients

Outcome Measures

Primary Outcome Measures

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

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
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 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.
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).
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.
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).
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patient ≥ 18 years and < 70 years of age at the time of signing the informed consent form (ICF)
Patient fit enough to receive autologous stem cell transplant as a consolidation strategy as assessed by the local investigator
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

Ann Arbor staging (I-IV) except stage I with normal LDH and PS<2 (i.e. stage I aaIPI

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)
FFPE Diagnostic tissue block should be available for central pathology review and ancillary molecular analyses
Participant with Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2
Estimated minimum life expectancy of 3 months
Patient who understood and voluntarily signed and dated an informed consent prior to any study-specific assessments/procedures being conducted
Able to adhere to the study visit schedule and other protocol requirements
Patient covered by any social security system (France)
Patient who understands and speaks one of the country official languages
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
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:

Known central nervous system or meningeal involvement by lymphoma
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.
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

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:
Basal or squamous cell carcinoma of the skin
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b) using the tumor, nodes, metastasis clinical staging system
Vaccinated with live, attenuated vaccines within 6 months of enrollment
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).
A corticosteroids therapy > 1mg/kg lasting more than 14 days prior to Cycle 1 Day 1
Positive serology for Human Immunodeficiency Virus (HIV) and Human T-Lymphotrophic Virus (HTLV1)
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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Chu D'Amiens - Hopital Sud	Amiens	France	80054
2	Chu D'Angers	Angers	France	49933
3	Ch Victor Dupouy	Argenteuil	France
4	Ch D'Avignon - Hopital Henri Duffaut	Avignon	France	84000
5	Ch de La Cote Basque	Bayonne	France	64109
6	Service d'Onco-radiolothérapie, Polyclinique Bordeaux Nord Aquitaine	Bordeaux	France	33300
7	Ch Metropole Savoie - Site Chambery	Chambéry	France	73000
8	Chu Estaing	Clermont-Ferrand	France
9	Ch Alpes Leman	Contamine sur Arve	France
10	Hopital Henri Mondor	Creteil	France	94010
11	René Olivier Casasnovas	Dijon	France	21000
12	CHU Francois MITTERRAND	Dijon	France
13	Ch de Dunkerque	Dunkerque	France
14	Chd de Vendee	La Roche-sur-Yon	France
15	Ch de Versailles - Hopital Andre Mignot	Le Chesnay	France
16	CHU du Mans	Le Mans	France
17	Service Oncologie médicale, HOPITAL SAINT VINCENT-DE-PAUL	Lille	France	59020
18	Service Hématologie Clinique et Thérapie Cellulaire, CHU DE LIMOGES - HOPITAL DUPUYTREN,	Limoges	France	87042
19	Centre Leon Berard	Lyon	France	69373
20	Chu de Montpellier	Montpellier	France
21	Chu de Nantes	Nantes	France
22	Centre Antoine Lacassagne	Nice	France	06189
23	Chu de Nimes - Hopital Caremeau	Nîmes	France
24	Chr Orleans	Orléans	France
25	Hopital Cochin	Paris	France	75014
26	Hopital de La Pitie Salpetriere	Paris	France	75651
27	Hopital Necker	Paris	France	75743
28	Hopital Saint Antoine	Paris	France
29	Ch de Perpignan	Perpignan	France
30	Chu de Bordeaux - Hopital Haut-Leveque	Pessac	France
31	Chu Lyon-Sud	Pierre Benite	France	69495
32	Ch Annecy Genevois	Pringy	France
33	Ch Perigueux	Périgueux	France
34	Chu Pontchaillou_Rennes	Rennes	France	35033
35	Ch de Roubaix - Hopital Victor Provo	Roubaix	France
36	Centre Henri Becquerel	Rouen	France	76038
37	Service Hématologie, Institut Curie - Hôpital René HUGUENIN	Saint-Cloud	France	92210
38	Chu de La Reunion - Hopital Felix Guyon	Saint-Denis	France
39	Chu de La Reunion - Ghsr	Saint-Pierre	France
40	Institut Cancerologie & Hematologie St-Etienne	Saint-Priest-en-Jarez	France	42270
41	Ch de Saint-Quentin	Saint-Quentin	France
42	Hôpitaux Universitaires de Strasbourg	Strasbourg	France
43	Institut Universitaire du Cancer	Toulouse	France
44	Chu Bretonneau	Tours	France
45	Ch de Valence	Valence	France
46	Ch de Valenciennes - Hopital Jean Bernard	Valenciennes	France
47	Chu Brabois	Vandœuvre-lès-Nancy	France	54511
48	Institut Gustave Roussy	Villejuif	France	94805