Cyclosporine Plus Methotrexate or Alemtuzumab

Phase 2

Terminated

• Conditions: Unrecognized Condition: Mature B or T-cell Neoplasm
• Interventions: Drug: Cyclosporine + METHOTREXATE; Drug: Cyclosporine + CAMPATH-1H

• Registration Number: NCT02701517
• Lead Sponsor: Grupo Español de Linfomas y Transplante Autólogo de Médula Ósea

Brief Summary

The primary aim of the study was to compare the efficacy of the procedure in terms of event-free survival between patients receiving cyclosporine (CsA) plus either alemtuzumab (CAMPATH-1H ) or methotrexate (MTX) after matched related donor allo-reduced intensity conditioning. Secondary aims were: 1. To compare the incidence of infections and transplant-related mortality between the two arms; 2. to compare the incidence of acute and chronic GVHD 3. to evaluate hematologic and immunologic reconstitution and evolution of chimerism and residual disease.

Patients were randomly assigned to received cyclosporine plus alemtuzumab or cyclosporine plus MTX and were stratified according to diagnosis: Chronic lymphocytic leukemia or Low grade- non-Hodgkin's lymphoma.

All patients received the same reduced-intensity conditioning (RIC) scheme based on fludarabine 150mg/m2 (30 mg/m2/day everyday from -8 to -4) plus melphalan 140mg/m2 (70 mg/m2/day everyday from -3 to -2). Regarding the GVHD prophylaxis, patients in group 1 (n=17) received CsA 1 mg/kg intravenously starting on day -7 and 2/mg/Kg from day -1 plus alemtuzumab administered at a dose of 20 mg IV on -8 to -4 whereas in group 2 (n=23) pts received CsA at same doses as group 1 plus MTX given at a dose of 15 mg/m2 intravenously on days 1 and 10 mg/m2 on days 3, 6 and 11, followed by folinic acid rescue (15 mg in +1 and 10 mg in +3, +6 and +11 intravenously every 6 hours for 4 doses starting 24 hours after each dose of MTX).

Acute and chronic GVHD were similarly graded by established criteria \[20, 21\]. In patients receiving alemtuzumab, CsA was suspended by day +130. They also received donor lymphocyte infusion (DLI) at a dose of 1 x 107 cluster of differentiation 3 / kg on day +180 in case of active disease, persistence of minimal residual disease detected by flow cytometry or mixed chimerism and no GVHD. In case mixed chimerism, donor lymphocyte infusion was performed if patient hematopoiesis progressively increased. In patients receiving CsA + MTX, CsA was suspended by day +180. These patients received DLI only in situations specified above.

The statistical analysis has been designed to identify a 20% difference in terms of disease-free survival (based on the increased incidence of relapse in patients receiving T-cell depletion).

Detailed Description

Not available

Study Timeline

• Study Start: 2003-09
• Primary Completion: 2009-11
• Study Completion: 2009-11
• Study First Submitted: 2015-03-12
• Study First Submitted QC: 2016-03-02
• Study First Posted: 2016-03-08
• Status Verified: 2017-12
• Last Update Submitted: 2017-12-28
• Last Update Posted: 2017-12-29

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cyclosporine + METHOTREXATE	Cyclosporine + METHOTREXATE	MTX days +1, +3, +6 and +11 followed by folinic acid rescue. All patients will receive CSA from day -7.
Cyclosporine + CAMPATH-1H	Cyclosporine + CAMPATH-1H	CAMPATH-1H at a dose of 20 mg / day at 8-hour intravenous infusion on days -8 to -4. All patients will receive CSA from day -7.

Primary Outcome Measures

Name	Time	Method
Efficacy of transplantation in terms of event-free survival	From +270 days	To compare the efficacy of transplantation in terms of event-free survival between patients receiving CAMPATH-1H or methotrexate in allogeneic related donor with nonmyeloablative conditioning.

Secondary Outcome Measures

Name	Time	Method
Incidence of infections and transplant-related mortality	1 year	Compare the incidence of infections and transplant-related mortality between the two arms

Trial Locations

Locations (5)

Department of Propedeutic Oncology, Medical University of Gdansk; 🇵🇱 Gdansk, Poland

Hospital Universitario de Salamanca; 🇪🇸 Salamanca, Spain

Clinical Hematology Department. ICO-Hospital Germans Trias i Pujol. Jose Carreras Research Institute; 🇪🇸 Badalona, Barcelona, Spain

Santa Creu I Sant Pau Hospital; 🇪🇸 Barcelona, Spain

Hospital Clinic I Provincial; 🇪🇸 Barcelona, Spain