Intensive Chemo-immunotherapy as First Line Treatment in Adult Patients With Peripheral T- Cell Lymphoma

NCT ID: NCT01679860

Last Updated: 2012-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 92 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2012-08-31

Brief Summary

Peripheral T cell lymphomas (PTCL) are a rare hematologic disease. Five-year overall survival (OS) of PTCL patients (pts) ranges between 20 and 30%. Allogeneic stem cell transplantation (allo-STC) may have a curative role for these pts but its toxicity is high when myeloablative conditioning is used. Reduced intensity conditionings (RIC) can decrease transplant related toxicity and mortality. The investigators have recently proved feasibility and potential efficacy of a RIC regimen in relapsed PTCL patients.

We want to investigate whether it is possible to improve the outcome of alk negative PTCL pts, stage II-IV at diagnosis, by intensifying the therapeutic approach.

The intensification will be obtained by combining intensive chemotherapy, alemtuzumab (anti-CD52 humanised antibody) and auto- or allo-SCT in pts aged between 18 and 60 years (Clinical Study A) or adding alemtuzumab to standard chemotherapy (CHOP) in pts aged between 61 and 70 years(Clinical Study B).

Detailed Description

Inclusion criteria Clin A

• Age ≥18 < or =60 years (patients older than 60 years are excluded because of the intensive chemotherapy and transplant procedures)
• Histologically proven diagnosis of PTCL, including the following categories: PTCL-U (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma),intestinal T - NHL
• Advanced stage disease (stage II-IV) or stage I and aaIPI score ≥ 2
• Written informed consent

Inclusion criteria Clin B

• Age >60 and ≤75 years (patients older than 75 years are excluded because of the intensive chemo-immunotherapy program)
• Histological proven diagnosis of PTCL, including the following categories: PTCL-U (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma), intestinal T - NHL
• Advanced-stage disease (stage II-IV) or stage I and aaIPI score ≥ 2
• Informed written consent

In clinical study A (Clin A) we are planning to evaluate the efficacy and the feasibility of an intensified chemo-immunotherapy program including auto-SCT or RIC allo-SCT in advanced stage PTCL pts ≥ 18 and < or = 60 years.

In clinical study B (Clin B) we intend to verify the efficacy and the feasibility of a combined immuno-chemotherapy approach in a subset of elderly pts aged > 60 and < or = 75 years.

Conditions

Lymphoma, T-Cell, Peripheral

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Clin A

Clin A. CHOP-Campath (CHOP-C) for 2 cycles , Hyper-C-Hidam for 2 cycles and auto-SCT (stem cell transplantation) or RIC allo-SCT in advanced stage PTCL pts ≥ 18 and ≤ 60 years

Group Type: EXPERIMENTAL

Clin A. CHOP-CAMPATH (Chemo-immunotherapy) + SCT

Intervention Type: PROCEDURE

Clin A:

• CHOP-Campath (CHOP-C) for 2 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO on days +1 to +5; Campath-1H (alemtuzumab) dose escalation 3-10-20mg IV days - 2, - 1, 0 (first CHOP-C) or 30mg SC day 0 (second CHOP-C). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on days + 1 and 21 (first and second CHOP-C).
• HYPER-C-HiDAM for 2 cycles: Methotrexate 1.5gr/m2 day +1; Cyclophosphamide 300mg/m2 every 12 hours days +2-3-4; ARA-C 2gr/m2 every 12 hours days +2-3-4; G-CSF 5μcg/kg/day starting from day +5 until peripheral blood stem cell harvest
• Myeloablative regimen followed by autologous transplantation or Reduced intensity conditioning followed by allogeneic transplantation.

Clin B

Clin B: CHOP-Campath (CHOP-C) for 6 cycles . It is a combined immunochemotherapy approach in a subset of elderly pts aged \> 60 ≤ 75 years

Group Type: EXPERIMENTAL

Clin B (CHOP- CAMPATH) Chemo-immunotherapy

Intervention Type: DRUG

Clin B:

• CHOP-Campath (CHOP-C) for 6 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO from day +1 to day +5¸ Campath-1H (alemtuzumab) 3-10mg IV on days - 1 and 0 ( first CHOP-C course) or 10mg SC on day 0 (for the following 5 C-CHOP courses). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on day +1 of each CHOP-C course.

Interventions

Clin A. CHOP-CAMPATH (Chemo-immunotherapy) + SCT

Clin A:

• CHOP-Campath (CHOP-C) for 2 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO on days +1 to +5; Campath-1H (alemtuzumab) dose escalation 3-10-20mg IV days - 2, - 1, 0 (first CHOP-C) or 30mg SC day 0 (second CHOP-C). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on days + 1 and 21 (first and second CHOP-C).
• HYPER-C-HiDAM for 2 cycles: Methotrexate 1.5gr/m2 day +1; Cyclophosphamide 300mg/m2 every 12 hours days +2-3-4; ARA-C 2gr/m2 every 12 hours days +2-3-4; G-CSF 5μcg/kg/day starting from day +5 until peripheral blood stem cell harvest
• Myeloablative regimen followed by autologous transplantation or Reduced intensity conditioning followed by allogeneic transplantation.

Intervention Type: PROCEDURE

Clin B (CHOP- CAMPATH) Chemo-immunotherapy

Clin B:

• CHOP-Campath (CHOP-C) for 6 cycles (every 21 days): Doxorubicin 50mg/m2 day +1, Vincristin 1.4mg/m2 day +1, Cyclophosphamide 750mg/m2 day +1, prednisone 100mg/m2 PO from day +1 to day +5¸ Campath-1H (alemtuzumab) 3-10mg IV on days - 1 and 0 ( first CHOP-C course) or 10mg SC on day 0 (for the following 5 C-CHOP courses). Methotrexate 12.5mg IT, Ara-C 40mg IT, Dexamethasone 4mg IT on day +1 of each CHOP-C course.

Intervention Type: DRUG

Other Intervention Names

Mab - Campath (Alemtuzumab); Mab- Campath (Alemtuzumab)

Eligibility Criteria

Inclusion Criteria

• Age ≥18 <60 years (patients older than 60 years are excluded because of the intensive chemotherapy and transplant procedures)
• Histologically proven diagnosis of PTCL, including the following categories: PTCL-U (peripheral T-cell lymphoma, unspecified), AILD-T (angioimmunoblastic-like T-cell lymphoma), ALKneg ALCL (ALK-negative anaplastic large cell lymphoma),intestinal T - NHL
• Advanced stage disease (stage II-IV) or stage I and aaIPI score ≥ 2
• Written informed consent

Exclusion Criteria

• Histological PTCL subset other than PTCL-U, AILD-T ALCL-ALKneg, intestinal T - NHL
• Central nervous system localization
• Positive serologic markers for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection
• Serum bilirubin levels > 2 the upper normal limit
• Clearance of creatinine < 50 ml/min
• DLCO < 50%
• Ejection fraction < 45% (or myocardial infarction in the last 12 months)
• Pregnancy or lactation
• Patient not agreeing to take adequate contraceptive measures during the study
• Psychiatric disease
• Any active, uncontrolled infection
• Type I hypersensitivity or anaphylactic reactions to proteins drugs
• Active secondary malignancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Paolo Corradini

Director Hematology and BMT Unit

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

paolo corradini

Role: PRINCIPAL_INVESTIGATOR

fondazione IRCCS istituto nazionale tumori Milano

Locations

Spedali Civili di Brescia

Brescia, Brescia, Italy

Azienda Ospedale Vittorio Emanuele Ferrarorro S. Bambino- Università di Catania

Catania, Catania, Italy

Ospedale San Carlo

Potenza, Potenza, Italy

Azienda Ospedaliera S. Luigi

Orbassano, Torino, Italy

Azienda OspedalieraSan Giovanni Battista

Torino, Torino, Italy

Università di Torino- Azienda Ospedaliera S. Giovanni Battista

Torino, Torino, Italy

Policlinico Universitario Udine

Udine, Udine, Italy

Ospedale SS. Antonio e Biagio e Cesare Arrigo

Alessandria, , Italy

University of Ancona - Division of Hematology

Ancona, , Italy

Ospedale Riuniti, Bergamo - Division of Hematology

Bergamo, , Italy

Ospedale Generale Regionale Bolzano

Bolzano, , Italy

Ospedale S. Croce - Division of Hematology

Cuneo, , Italy

Ospedale San Raffaele, Milano - Division of Hematology

Milan, , Italy

Division of Hematology - Fondazione IRCCS Istituto Nazionale Tumori

Milan, , Italy

IRCCS Ospedale Maggiore Policlinico di Milano

Milan, , Italy

Ospedale Cervello - Bone Marrow Transplantation Unit

Palermo, , Italy

Azienda Ospedaliera Policlinico di Verona

Verona, , Italy

Countries

Italy

Other Identifiers

PTCL-062006-004234-33

Identifier Type: -

Identifier Source: org_study_id