Clinical trial NCT02520908: Benefit of Allogeneic Haematopoietic Stem Cells in Cutaneous T-cell Lymphomas Epidermotropic With Advanced Stage and Poor Prognosis
Official title: 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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Epidermotropic T-cell Lymphomas
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-08-13
Enrollment: 98
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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).


Eligibility criteria: 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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 3 year
Secondary outcomes:
measure: overall survival (OS)
timeFrame: 3 year
measure: Neutrophils Engraftment
timeFrame: 180 days
measure: Acute and chronic graft-versus-host disease (GVHD)
timeFrame: 180 days
measure: Cumulative incidence of relapse
timeFrame: 3 years
measure: Treatment-related mortality (TRM)
timeFrame: 12 months
measure: Quality of life (QoL)
timeFrame: 3 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Saint Louis hospital
Study officials:
References:
citation: de Masson A, Beylot-Barry M, Ram-Wolff C, Mear JB, Dalle S, d'Incan M, Ingen-Housz-Oro S, Orvain C, Abraham J, Dereure O, Charbonnier A, Cornillon J, Longvert C, Barete S, Boulinguez S, Wierzbicka-Hainaut E, Aubin F, Rubio MT, Bernard M, Schmidt-Tanguy A, Houot R, Pham-Ledard A, Michonneau D, Brice P, Labussiere-Wallet H, Bouaziz JD, Grange F, Moins-Teisserenc H, Jondeau K, Michel L, Mourah S, Battistella M, Daguindau E, Loschi M, Picard A, Franck N, Maillard N, Huynh A, Nguyen S, Marcais A, Chaby G, Ceballos P, Le Corre Y, Maury S, Bay JO, Adamski H, Bachy E, Forcade E, Socie G, Bagot M, Chevret S, Peffault de Latour R; CUTALLO Investigators; Groupe Francais d'Etude des Lymphomes Cutanes; Societe Francaise de Greffe de Moelle et Therapie Cellulaire. Allogeneic transplantation in advanced cutaneous T-cell lymphomas (CUTALLO): a propensity score matched controlled prospective study. Lancet. 2023 Jun 10;401(10392):1941-1950. doi: 10.1016/S0140-6736(23)00329-X. Epub 2023 Apr 24.