High-dose Chemotherapy With Transplantation of Gene-modified Haematopoietic Stem Cells for HIV-positive Patients With Malignant Diseases Indicating an HSCT

Study Overview
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Brief Summary
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Patient stem cells will be mobilized with induction chemotherapy (R)-ICE and G-CSF. If sufficient cells can be mobilized, patients will be treated with high-dose chemotherapy and a transplant of autologous CD34+ cells transduced with an antiviral vector (M87o). If autologous CD34+ yield is insufficient, allogeneic gene-modified cells will be given, if a compatible donor is available. To minimize risk of transplant failure, a second unmodified CD34+ cell transplant will be given one week after the first transplant.

Official Title
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High-dose Chemotherapy With Transplantation of Gene-modified Haematopoietic Stem Cells for HIV-positive Patients With Malignant Diseases Indicating an HSCT

Conditions
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AIDS-related Lymphoma, HIV Infections

Intervention / Treatment
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* Procedure: PBSC-M87o, Gene (M87o)-modified, CD34+ peripheral blood progenitor cells (PBSC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients of any ethnic group aged between 18 and 65 years HIV-positive patients with malignant diseases of the blood (NHL, Hodgkin disease, plasmocytoma, acute and chronic leukaemia) who failed to achieve complete remission (CR) after standard-dose first-line chemotherapy or had a chemosensitive relapse after an initial CR Patients must receive HAART Exclusion Criteria: Any of the following conditions: congestive heart failure (NYHA > II) documented EBV, HBV or HCV infection (only for allogeneic PBSCT) creatinine clearance < 60 ml/min left ventricular ejection fraction < 40% bilirubin > 2 mg/dl Severe opportunistic infection More than 10% of bone marrow involved with lymphoma Between 2 and 5 10^6 autologous CD34+ cells/kg BW obtained after leukapheresis and CD34 enrichment Women of child.bearing potential not under adequate contraceptive protection Women who are pregnant or breast feeding Known history of drug-, medication- or alcohol abuse within the last 12 months preceding the study Participation in another study with an investigational product within less than one month prior to this study Simultaneous participation in a study with an investigational drug Presence of any disease likely to require procedures altering the schedule of the protocol Patients with a history of seizures, central nervous system disorders or psychiatric disability thought to be clinically significant in the opinion of the investigator Patients with limited mental capacity to the extent that he/she cannot provide informed consent or information regarding adverse events of the study medication Patients with any clinically meaningful renal, hepatic, respiratory or cardiovascular disease Patients who have previously been admitted to this study Patients who will not accept transfusions of blood products

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Procedure: PBSC-M87o, Gene (M87o)-modified, CD34+ peripheral blood progenitor cells (PBSC)<br>* Patient stem cells will be mobilized with induction chemotherapy (R)-ICE and G-CSF. If sufficient cells can be mobilized, patients will be treated with high-dose chemotherapy and a transplant of autologous CD34+ cells transduced with an antiviral vector (M87o). If autologous CD34+ yield is insufficient, allogeneic gene-modified cells will be given, if a compatible donor is available. To minimize risk of transplant failure, a second unmodified CD34+ cell transplant will be given one week after the first transplant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events, ECOG performance status and laboratory safety tests |  | five years after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission status (CR or PR) |  | five years after transplantation | 
| Any relapse of ARL |  | five years after transplantation | 
| level and kinetics of engraftment and level of gene marking |  | five years after transplantation | 
| Viral load |  | five years after transplantation | 
| CD4 counts |  | five years after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS, HIV, Lymphoma, Stem Cell Transplantation, gene-modified Stem Cells, treatment experienced