Therapeutic Intensification of HIV-associated Non-Hodgkin's Lymphoma by Peripheral Blood Cell Transplantation Following Chemotherapy.

Therapeutic Intensification for HIV-associated Non-Hodgkin's Lymphoma by Autologous Transplantation of Either Unselected or CD34+-Selected Peripheral Blood Stem Cells, in Patients in First or Second Complete Remission. ANRS 131

Given the poor prognosis of HIV-associated non-Hodgkin's lymphoma (NHL) and it's still high incidence in HAART era, more intensive therapy is required in patients with initially severe stage of NHL or relapsing after first-line chemotherapy.

The purpose of this study is to evaluate the safety of an intensive chemotherapy followed by peripheral blood cell transplantation in these patients.

Study Overview

• Status: Terminated
• Conditions: HIV Infections; Lymphoma, Non-Hodgkin
• Intervention / Treatment: Procedure: autologous peripheral blood cell transplantation

Detailed Description

Highly active antiretroviral therapy (HAART) has dramatically reduced mortality and morbidity of HIV-infected patients by decreasing the incidence of opportunistic infections and HIV-related malignancies such as Kaposi sarcoma. However, the frequency of NHL remains increased in these patients. Moreover, their prognostic remains poor comparing to HIV negative patients. This is mainly due to the type of NHL (aggressive B, and frequent stage IV) but also host factors such as immunodeficiency, co-infections (EBV, HHV8), and chemotherapy-HAART interactions. In the lack of new and significantly more efficient treatments, therapeutic intensification such as high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (ASCT), already tested in relapsed or partially responding HIV negative patients, could be an option in HAART controlled HIV+ patients with NHL, rather in first complete remission (CR) but with initially high International Prognosis Index (IPI above or equal to 2), or in second CR, whatever initial IPI. Positive selection CD34+ cells is an approach for depleting grafts of tumour cells and HIV DNA. However the delayed lymphocyte recovery following this process, may lead to increased incidence of opportunistic infections (OI) in HIV-infected patients. OI prophylaxis will be systematically associated.

Eligible patients will have peripheral blood stem cell (PBSC) mobilization and divided in two subgroups. Group A with 3-6 x 106 PBSC will not undergo CD34+ selection process and group B with more than 6 x 106 will undergo this process. The myeloablative conditioning process is the same in the two groups with total body irradiation before reinfusion of grafts.

Patients will be followed from week2 (W2) up to W60 with clinical and biological evaluations.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Servide d'Immunologie Clinique

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients between 18 and 55 years old at screening
• Documented HIV-1 infection
• Currently HAART-treated
• Plasma HIV-RNA below 50 copies/ml at screening
• Lymphocyte T CD4+ count above or equal to 100/mm3 at the NHL diagnosis
• Histologically proven large cell NHL in first remission with classical poor prognostic factors (IPI above or equal to 2) or in second remission whatever IPI.
• Biological criteria of eligibility for intensive therapeutic
• Signed written informed consent
• Patient protected by the social security of one of the European community countries.

Exclusion Criteria:

• Burkitt NHL
• Central nervous system NHL
• Patients already treated by ASCT
• Ongoing infectious disease
• Psychiatric disease
• Left ventricular ejection fraction < 25%
• Creatinine clearance < 50 ml/min
• Hepatic failure
• Uncontrolled high blood pressure
• Chronic hepatitis C or B
• Participating in other trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety criteria defined as the occurrence of grades 3 or 4 adverse events in the 6 months following transplantation.

Secondary Outcome Measures

Outcome Measure
Evaluation of:
HIV RNA
HIV DNA
Percentage and absolute count of CD3, CD4+ and CD8+ lymphocytes
Lymphocyte phenotypes and functions
TREC analysis
Immune reconstitution in vivo
Duration of aplasia

Collaborators and Investigators

• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Investigators: Principal Investigator: Yves LEVY, MD, PhD, Service d'Immunologie Clinique, Henri Mondor Hospital 94010 Creteil Cedex; Study Director: Genevieve CHENE, MD, PhD, INSERM Unit 593, Bordeaux

Study record dates

Study Major Dates

• Study Start: February 1, 2007
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): October 1, 2008

Study Registration Dates

• First Submitted: February 5, 2007
• First Submitted That Met QC Criteria: February 5, 2007
• First Posted (Estimate): February 7, 2007

Study Record Updates

• Last Update Posted (Estimate): December 22, 2011
• Last Update Submitted That Met QC Criteria: December 21, 2011
• Last Verified: December 1, 2011

More Information

Terms related to this study

• Keywords: HIV; Non-Hodgkin's lymphoma; Peripheral blood stem cells transplantation
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: ANRS131