High-Dose Chemotherapy With Transplantation of Gene-Modified Stem Cells for High-Risk AIDS-Related Lymphoma

• Remission status (CR or PR) [ Time Frame: five years after transplantation ] [ Designated as safety issue: No ]
• Any relapse of ARL [ Time Frame: five years after transplantation ] [ Designated as safety issue: No ]
• level and kinetics of engraftment and level of gene marking [ Time Frame: five years after transplantation ] [ Designated as safety issue: No ]
• Viral load [ Time Frame: five years after transplantation ] [ Designated as safety issue: No ]
• CD4 counts [ Time Frame: five years after transplantation ] [ Designated as safety issue: No ]

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.

• AIDS-Related Lymphoma
• HIV Infections

Inclusion Criteria:

• Male and female patients of any ethnic group aged between 18 and 65 years
• HIV-positive patients with NHL 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 < 50%
  • bilirubin > 2 mg/dl
• Not-treated opportunistic infection
• Not-treated CNS involvement of lymphoma
• Isolated CNS relapse of the lymphoma without other evidence of active disease
• 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