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

Lymphoma, T-Cell, Peripheral Clinical Trial

— PTCL-06  

Official title:

Intensive Chemo-immunotherapy as First-line Treatment in Adult Patients With Peripheral T-cell Lymphoma (PTCL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01679860
• Other study ID #: PTCL-062006-004234-33
• Status: Completed
• Phase: Phase 2
• First received: August 30, 2012
• Last updated: September 3, 2012
• Start date: November 2006
• Est. completion date: August 2012

Study information

• Verified date: September 2012
• Source: Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: The Italian Medicines Agency
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 92
• Est. completion date: August 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral

Intervention

Procedure:
• 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.

Drug:
• 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.

Locations

Country	Name	City	State
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	Spedali Civili di Brescia	Brescia
Italy	Azienda Ospedale Vittorio Emanuele Ferrarorro S. Bambino- Università di Catania	Catania
Italy	Ospedale S. Croce - Division of Hematology	Cuneo
Italy	Division of Hematology - Fondazione IRCCS Istituto Nazionale Tumori	Milan
Italy	Ospedale San Raffaele, Milano - Division of Hematology	Milan
Italy	IRCCS Ospedale Maggiore Policlinico di Milano	Milano
Italy	Azienda Ospedaliera S. Luigi	Orbassano	Torino
Italy	Ospedale Cervello - Bone Marrow Transplantation Unit	Palermo
Italy	Ospedale San Carlo	Potenza
Italy	Azienda OspedalieraSan Giovanni Battista	Torino
Italy	Università di Torino- Azienda Ospedaliera S. Giovanni Battista	Torino
Italy	Policlinico Universitario Udine	Udine
Italy	Azienda Ospedaliera Policlinico di Verona	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy	number of clinical responses	one year	No
Secondary	evaluation of OS (overall survival)	OS time is calculated from patients enrollment to death for all causes; censored cases are pts alive at the date of last follow-up assessment.	4 years	Yes
Secondary	DFS (Disease Free Survival)	DFS time is the interval between CR achievement and the first disease relapse or death regardless of the cause.Definition of disease response/progression will be performed according to the criteria published by Juweid et al.(J Clin Oncol. 2005; 23: 4652-61)	4 years	No
Secondary	TRM (Treatment Related Mortality)	TRM will be analysed by computing the corresponding crude cumulative incidence curve, considering disease-related death as competing event.	4 years	Yes