Transplantation After Complete Response In Patients With T-cell Lymphoma
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Peripheral T Cell Lymphoma
- Sponsor
- Hospices Civils de Lyon
- Enrollment
- 204
- Locations
- 48
- Primary Endpoint
- 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
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
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 0)
- •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
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
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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)
- 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)
- To Evaluate PET-CT 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(After four cycles of chemotherapy (each cycle is 3weeks))
- 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)
- 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))
- 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)
- 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)
- 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))
- 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)
- 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))
- To evaluate the predictive value of total metabolic tumor volume (TMTV) on PET-CT(at patient enrollment)