PTCL-06: Intensive Chemo-immunotherapy as First Line Treatment in Adult Patients With Peripheral T- Cell Lymphoma

Sponsor

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano (Other)

Overall Status

Completed

CT.gov ID

NCT01679860

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

5.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Lymphoma, T-Cell, Peripheral	Procedure: Clin A. CHOP-CAMPATH (Chemo-immunotherapy) + SCT Drug: Clin B (CHOP- CAMPATH) Chemo-immunotherapy	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

92 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2006

Actual Primary Completion Date :

Dec 1, 2011

Actual Study Completion Date :

Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	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. Other Names: Mab - Campath (Alemtuzumab)
Experimental: 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	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. Other Names: Mab- Campath (Alemtuzumab)

Arm

Intervention/Treatment

Experimental: 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

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.

Other Names:

Mab - Campath (Alemtuzumab)

Experimental: 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

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.

Other Names:

Mab- Campath (Alemtuzumab)

Outcome Measures

Primary Outcome Measures

Efficacy [one year]
number of clinical responses

Secondary Outcome Measures

evaluation of OS (overall survival) [4 years]
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.
DFS (Disease Free Survival) [4 years]
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)
TRM (Treatment Related Mortality) [4 years]
TRM will be analysed by computing the corresponding crude cumulative incidence curve, considering disease-related death as competing event.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Azienda Ospedaliera S. Luigi	Orbassano	Torino	Italy	10043
2	Ospedale SS. Antonio e Biagio e Cesare Arrigo	Alessandria		Italy	15100
3	University of Ancona - Division of Hematology	Ancona		Italy	62020
4	Ospedale Riuniti, Bergamo - Division of Hematology	Bergamo		Italy	24128
5	Ospedale Generale Regionale Bolzano	Bolzano		Italy	39100
6	Spedali Civili di Brescia	Brescia		Italy	25123
7	Azienda Ospedale Vittorio Emanuele Ferrarorro S. Bambino- Università di Catania	Catania		Italy	94124
8	Ospedale S. Croce - Division of Hematology	Cuneo		Italy	12100
9	IRCCS Ospedale Maggiore Policlinico di Milano	Milano		Italy	20122
10	Ospedale San Raffaele, Milano - Division of Hematology	Milan		Italy	20100
11	Division of Hematology - Fondazione IRCCS Istituto Nazionale Tumori	Milan		Italy	20133
12	Ospedale Cervello - Bone Marrow Transplantation Unit	Palermo		Italy
13	Ospedale San Carlo	Potenza		Italy	85100
14	Azienda OspedalieraSan Giovanni Battista	Torino		Italy	10126
15	Università di Torino- Azienda Ospedaliera S. Giovanni Battista	Torino		Italy	10126
16	Policlinico Universitario Udine	Udine		Italy
17	Azienda Ospedaliera Policlinico di Verona	Verona		Italy	37134