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

Prospective, Controlled, Multicenter Cohort Study Evaluating the Benefit of Allogeneic Haematopoietic Stem Cells in Cutaneous T-cell Lymphomas Epidermotropic With Advanced Stage and Poor Prognosis

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Epidermotropic T-cell Lymphomas
• Intervention / Treatment: Procedure: HSCT; Other: Standard Care

• Study Type: Observational
• Enrollment (Actual): 98

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Saint Louis Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Advanced-stage epidermotropic T-cell lymphomas (ETCL), i.e. mycosis fungoides (MF) and its leukemic variant, Sézary syndrome

Description

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 Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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	Procedure: HSCT; Hematopoietic stem cell transplantation
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	Other: Standard Care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-Free Survival (PFS)	3 year

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2016
• Primary Completion (Anticipated): November 19, 2024
• Study Completion (Anticipated): November 19, 2024

Study Registration Dates

• First Submitted: July 27, 2015
• First Submitted That Met QC Criteria: August 7, 2015
• First Posted (Estimate): August 13, 2015

Study Record Updates

• Last Update Posted (Actual): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 15, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous
• Other Study ID Numbers: NI 14018