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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00432419
• Other study ID #: ANRS131
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: February 5, 2007
• Last updated: December 21, 2011
• Start date: February 2007
• Est. completion date: October 2008

Study information

• Verified date: December 2011
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: October 2008
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• HIV Infections
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Procedure:
• autologous peripheral blood cell transplantation

Locations

Country	Name	City	State
France	Servide d'Immunologie Clinique	Creteil

Sponsors (1)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety criteria defined as the occurrence of grades 3 or 4 adverse events in the 6 months following transplantation.
Secondary	Evaluation of:
Secondary	HIV RNA
Secondary	HIV DNA
Secondary	Percentage and absolute count of CD3, CD4+ and CD8+ lymphocytes
Secondary	Lymphocyte phenotypes and functions
Secondary	TREC analysis
Secondary	Immune reconstitution in vivo
Secondary	Duration of aplasia