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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Paolo Corradini, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier:
NCT01679860
First received: August 30, 2012
Last updated: September 3, 2012
Last verified: September 2012
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Intensive Chemo-immunotherapy as First-line Treatment in Adult Patients With Peripheral T-cell Lymphoma (PTCL)

Resource links provided by NLM:


Further study details as provided by Fondazione IRCCS Istituto Nazionale dei Tumori, Milano:

Primary Outcome Measures:
  • Efficacy [ Time Frame: one year ] [ Designated as safety issue: No ]
    number of clinical responses


Secondary Outcome Measures:
  • evaluation of OS (overall survival) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 4 years ] [ Designated as safety issue: No ]
    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) [ Time Frame: 4 years ] [ Designated as safety issue: Yes ]
    TRM will be analysed by computing the corresponding crude cumulative incidence curve, considering disease-related death as competing event.


Enrollment: 92
Study Start Date: November 2006
Study Completion Date: August 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Mab- Campath (Alemtuzumab)

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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01679860

Locations
Italy
Azienda Ospedaliera S. Luigi
Orbassano, Torino, Italy, 10043
Ospedale SS. Antonio e Biagio e Cesare Arrigo
Alessandria, Italy, 15100
University of Ancona - Division of Hematology
Ancona, Italy, 62020
Ospedale Riuniti, Bergamo - Division of Hematology
Bergamo, Italy, 24128
Ospedale Generale Regionale Bolzano
Bolzano, Italy, 39100
Spedali Civili di Brescia
Brescia, Italy, 25123
Azienda Ospedale Vittorio Emanuele Ferrarorro S. Bambino- Università di Catania
Catania, Italy, 94124
Ospedale S. Croce - Division of Hematology
Cuneo, Italy, 12100
Division of Hematology - Fondazione IRCCS Istituto Nazionale Tumori
Milan, Italy, 20133
Ospedale San Raffaele, Milano - Division of Hematology
Milan, Italy, 20100
IRCCS Ospedale Maggiore Policlinico di Milano
Milano, Italy, 20122
Ospedale Cervello - Bone Marrow Transplantation Unit
Palermo, Italy
Ospedale San Carlo
Potenza, Italy, 85100
Università di Torino- Azienda Ospedaliera S. Giovanni Battista
Torino, Italy, 10126
Azienda OspedalieraSan Giovanni Battista
Torino, Italy, 10126
Policlinico Universitario Udine
Udine, Italy
Azienda Ospedaliera Policlinico di Verona
Verona, Italy, 37134
Sponsors and Collaborators
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
Investigators
Principal Investigator: paolo corradini fondazione IRCCS istituto nazionale tumori Milano
  More Information

No publications provided

Responsible Party: Paolo Corradini, Director Hematology and BMT Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano
ClinicalTrials.gov Identifier: NCT01679860     History of Changes
Other Study ID Numbers: PTCL-062006-004234-33
Study First Received: August 30, 2012
Last Updated: September 3, 2012
Health Authority: Italy: The Italian Medicines Agency

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Alemtuzumab
Campath 1G
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 24, 2014