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

September 26, 2023 updated by: Hospices Civils de Lyon

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

204

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Amiens, France, 80054
        • Not yet recruiting
        • Chu D'Amiens - Hopital Sud
        • Principal Investigator:
          • Caroline DELETTE
        • Contact:
      • Angers, France, 49933
      • Argenteuil, France
      • Avignon, France, 84000
        • Not yet recruiting
        • CH d'Avignon - Hopital Henri Duffaut
        • Contact:
        • Principal Investigator:
          • Hacène ZERAZHI, MD
      • Bayonne, France, 64109
        • Not yet recruiting
        • CH de la Côte Basque
        • Contact:
        • Principal Investigator:
          • Sophie BERNARD
      • Bordeaux, France, 33300
        • Not yet recruiting
        • Service d'Onco-radiolothérapie, Polyclinique Bordeaux Nord Aquitaine
        • Contact:
        • Principal Investigator:
          • Olivier FITOUSSI
      • Chambéry, France, 73000
      • Clermont-Ferrand, France
      • Contamine sur Arve, France
        • Not yet recruiting
        • CH Alpes Léman
        • Contact:
        • Principal Investigator:
          • Blandine BOUTIN
      • Creteil, France, 94010
        • Not yet recruiting
        • Hopital Henri Mondor
        • Contact:
          • François LEMONNIER, MD
        • Principal Investigator:
          • François LEMONNIER
      • Dijon, France, 21000
        • Not yet recruiting
        • René Olivier Casasnovas
        • Principal Investigator:
          • Franck Morschhauser
        • Contact:
      • Dijon, France
        • Not yet recruiting
        • CHU Francois Mitterrand
        • Contact:
        • Principal Investigator:
          • René-Olivier Casasnovas, MD
      • Dunkerque, France
      • La Roche-sur-Yon, France
        • Not yet recruiting
        • CHD de Vendée
        • Contact:
        • Principal Investigator:
          • Stéphane VIGOUROUX
      • Le Chesnay, France
        • Not yet recruiting
        • CH de Versailles - Hôpital André Mignot
        • Contact:
        • Principal Investigator:
          • Milena KOHN
      • Le Mans, France
        • Not yet recruiting
        • CHU du Mans
        • Contact:
        • Principal Investigator:
          • Kamel Laribi
      • Lille, France, 59020
        • Not yet recruiting
        • Service Oncologie médicale, HOPITAL SAINT VINCENT-DE-PAUL
        • Contact:
        • Principal Investigator:
          • Sandy AMORIM
      • Limoges, France, 87042
        • Not yet recruiting
        • Service Hématologie Clinique et Thérapie Cellulaire, CHU DE LIMOGES - HOPITAL DUPUYTREN,
        • Contact:
        • Principal Investigator:
          • Julie Abraham
      • Lyon, France, 69373
      • Montpellier, France
        • Not yet recruiting
        • CHU de Montpellier
        • Contact:
        • Principal Investigator:
          • Charles HERBAUX
      • Nantes, France
      • Nice, France, 06189
      • Nîmes, France
        • Not yet recruiting
        • CHU de Nîmes - Hôpital Caremeau
        • Contact:
        • Principal Investigator:
          • Agathe WAULTIER - RASCALOU
      • Orléans, France
      • Paris, France, 75014
        • Not yet recruiting
        • Hopital Cochin
        • Contact:
        • Principal Investigator:
          • Bénédicte DEAU-FISCHER
      • Paris, France
        • Not yet recruiting
        • Hôpital Saint Antoine
        • Contact:
        • Principal Investigator:
          • Mohamad MOHTY
      • Paris, France, 75651
        • Not yet recruiting
        • Hopital de la Pitie Salpetriere
        • Contact:
        • Principal Investigator:
          • Sylvain CHOQUET
      • Paris, France, 75743
        • Not yet recruiting
        • Hopital Necker
        • Principal Investigator:
          • Ambroise Marcais
        • Contact:
      • Perpignan, France
      • Pessac, France
        • Not yet recruiting
        • CHU de Bordeaux - Hôpital Haut-Lévêque
        • Principal Investigator:
          • François-Xavier GROS
        • Contact:
      • Pierre Benite, France, 69495
      • Pringy, France
      • Périgueux, France
      • Rennes, France, 35033
        • Not yet recruiting
        • Chu Pontchaillou_Rennes
        • Contact:
        • Principal Investigator:
          • Roch HOUOT
      • Roubaix, France
        • Not yet recruiting
        • Ch de Roubaix - Hopital Victor Provo
        • Contact:
        • Principal Investigator:
          • Julia HIEULLE
      • Rouen, France, 76038
      • Saint-Cloud, France, 92210
        • Not yet recruiting
        • Service Hématologie, Institut Curie - Hôpital René HUGUENIN
        • Contact:
      • Saint-Denis, France
        • Not yet recruiting
        • Chu de La Reunion - Hopital Felix Guyon
        • Contact:
        • Principal Investigator:
          • Marie DE CHARRETTE
      • Saint-Pierre, France
        • Not yet recruiting
        • Chu de La Reunion - Ghsr
        • Contact:
        • Principal Investigator:
          • Hugo LEGENDRE
      • Saint-Priest-en-Jarez, France, 42270
        • Not yet recruiting
        • Institut Cancerologie & Hematologie St-Etienne
        • Contact:
        • Principal Investigator:
          • Jérôme CORNILLON
      • Saint-Quentin, France
        • Not yet recruiting
        • Ch de Saint-Quentin
        • Contact:
        • Principal Investigator:
          • Réda GARIDI
      • Strasbourg, France
        • Not yet recruiting
        • Hôpitaux Universitaires de Strasbourg
        • Principal Investigator:
          • Luc-Matthieu FORNECKER, MD
        • Contact:
      • Toulouse, France
        • Not yet recruiting
        • Institut universitaire du cancer
        • Principal Investigator:
          • Loïc Ysebaert, MD
        • Contact:
      • Tours, France
        • Not yet recruiting
        • CHU Bretonneau
        • Contact:
        • Principal Investigator:
          • Laurianne Drieu La Rochelle
      • Valence, France
      • Valenciennes, France
        • Not yet recruiting
        • Ch de Valenciennes - Hopital Jean Bernard
        • Contact:
        • Principal Investigator:
          • Sabine TRICOT
      • Vandœuvre-lès-Nancy, France, 54511
        • Not yet recruiting
        • CHU Brabois
        • Contact:
        • Principal Investigator:
          • Charline MOULIN
      • Villejuif, France, 94805

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of Overall survival (OS)
Time Frame: 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
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
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of Overall response rate (ORR) and Complete Response Rate (CRR)
Time Frame: 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).
At the end of ASCT (8-12 weeks after post-induction evaluation)
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of duration of Response (DoR)
Time Frame: 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.
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
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of time to next Treatment (TTNT)
Time Frame: 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.
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
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of quality of Life
Time Frame: 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.
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
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of cost-Effectiveness Analysis
Time Frame: 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).
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
Comparison of chemotherapy regimens + ASCT consolidation with chemotherapy regimens alone in terms of budget Impact Analysis
Time Frame: 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.
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
Adjusted comparison of chemotherapy regimens (CHOP vs CHOEP) in non-sALCL in terms of Overall Response Rate (ORR)
Time Frame: 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).
at the end of induction (between 3 and 5 weeks after the last drug administration)
Adjusted comparison of chemotherapy regimens (CHOP vs CHOEP) in non-sALCL in terms of Complete Response rate (CRR)
Time Frame: 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).
at the end of induction (between 3 and 5 weeks after the last drug administration)
To evaluate the predictive value of total metabolic tumor volume (TMTV) on PET-CT
Time Frame: at patient enrollment
Predictive value of TMTV on PET-CT
at patient enrollment
To Evaluate PET-CT Omics
Time Frame: at patient enrollment
PET-Omics
at patient enrollment
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
Time Frame: 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
After four cycles of chemotherapy (each cycle is 3weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Emmanuel BACHY, Pr, HCL

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2022

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

June 8, 2022

First Submitted That Met QC Criteria

June 29, 2022

First Posted (Actual)

July 6, 2022

Study Record Updates

Last Update Posted (Actual)

September 28, 2023

Last Update Submitted That Met QC Criteria

September 26, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 69HCL21_1095

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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