Benefit of Allogeneic Haematopoietic Stem Cells in Cutaneous T-cell Lymphomas Epidermotropic With Advanced Stage and Poor Prognosis

Active, not recruiting

• Conditions: Epidermotropic T-cell Lymphomas
• Interventions: Other: Standard Care; Procedure: HSCT

• Registration Number: NCT02520908
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Epidermotropic T-cell lymphomas (ETCL), i.e. mycosis fungoides (MF) and its leukemic variant, Sézary syndrome, are the most frequent subtypes of cutaneous T-cell lymphomas. MF typically runs an indolent course in its early stages. By contrast, advanced-stage ETCLs share a very bad prognosis: Patients usually show early relapses after chemotherapy, prolonged complete remissions exceptionally occur and quality of life is severely affected. Several publications have reported durable responses following allogeneic hematopoietic stem cell transplantation (HSCT) in advanced-stage ETCLs. This study aims to investigate the role of allogeneic HSCT in treating advanced-stage ETCLs. An observational, prospective, multicenter, controlled study will compare the outcomes of patients who receive reduced-intensity conditioned allogeneic HSCT from a sibling or 10/10 HLA-matched unrelated donor to those of patients who receive standard of care in patients with advanced-stage ETCL with poor prognostic features, will be performed. Patients are included at the time of donor search irrespective of the results, and compared on a donor versus no donor basis. It is an observational study since no intervention is made except the comparison of outcomes of groups that receive usual care (HSCT if donor available, or not).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-07-27
• Study First Submitted QC: 2015-08-07
• Study First Posted: 2015-08-13
• Study Start: 2016-09-23
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-29
• Last Update Posted: 2024-05-01
• Primary Completion: 2024-11-19
• Study Completion: 2024-11-19

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

• Age ≥ 18 and ≤ 65 years
• Histopathologically confirmed diagnosis of International Society for Cutaneous Lymphomas (ISCL) / European Organisation for Research and Treatment of Cancer (EORTC) stage IIB, III, IVA or IVB ETCL
• Complete or partial response of the lymphoma (as defined by the international ISCL-EORTC criteria at the time of inclusion
• Written informed consent given by the patient
• Contraception in women of childbearing age
• Hematopoietic stem cell donor search underway

And at least one of the three following criteria:

• Refractoriness or early relapse (i.e. within one year) after at least one line of systemic chemotherapy (not including skin-directed therapies, methotrexate, interferon-alpha, and oral retinoids)
• Early histological large-cell transformation, i.e. within two years following ETCL diagnosis
• Histologically proven nodal (ISCL / EORTC N3) or extra-cutaneous visceral involvement by the lymphoma

Exclusion Criteria

• Prior allogeneic HSCT
• Other progressive neoplastic disease
• Progressive psychotic disease
• Left ventricular ejection fraction < 50% (as determined by trans-thoracic echocardiography)
• Pulmonary disease with FEV1, FVC or DLCO <30% of expected corrected for hemoglobin.
• Creatinine clearance <50 ml/min or requiring dialysis
• Transaminases or bilirubin >two-fold the normal value in the absence of liver involvement by the lymphoma
• Pregnant or breastfeeding woman
• Patient with no health coverage
• Patient under guardianship or curatorship
• HTLV-1 lymphoma

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Standard care	Standard Care	Patients with no available sibling or 10/10 HLA-matched unrelated donor who therefore do not receive allogeneic HSCT but receive best standard of care treatment, will be included in the study, as the control group
HSCT	HSCT	Patients with an available sibling or 10/10 HLA-matched unrelated donor who undergo reduced-intensity conditioned allogeneic hematopoietic stem cell transplantation (HSCT), will be included in the study. The reduced-intensity conditioning usually includes Fludarabine 90 mg/m2 IV and Melphalan 140 mg/m2 IV. As usual care, patients will receive peripheral blood stem cells from their sibling donor if available, otherwise from their 10/10 HLA-matched unrelated donor

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	3 year

Secondary Outcome Measures

Name	Time	Method
Treatment-related mortality (TRM)	12 months
overall survival (OS)	3 year
Neutrophils Engraftment	180 days	Neutrophils \> 1,000 Giga/L
Acute and chronic graft-versus-host disease (GVHD)	180 days
Cumulative incidence of relapse	3 years
Quality of life (QoL)	3 years

Trial Locations

Locations (1)

Saint Louis hospital; 🇫🇷 Paris, France