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

Civil Hospices of Lyon

Status: Enrolling

Conditions: Peripheral T Cell Lymphoma

Treatments: Procedure: Chemotherapy + ASCT + follow up; Procedure: Chemotherapy + follow up

Study type: Interventional

Funder types: Other

Identifiers

NCT05444712

69HCL21_1095

Details and patient eligibility

About

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.

Enrollment: 204 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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)

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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204 participants in 2 patient groups

Chemotherapy

Active Comparator group

Description:

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)

Treatment:

Procedure: Chemotherapy + follow up

Chemotherapy + ASCT

Active Comparator group

Description:

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

Treatment:

Procedure: Chemotherapy + ASCT + follow up