Clinical trial NCT00858793: High-dose Chemotherapy With Transplantation of Gene-modified Haematopoietic Stem Cells for HIV-positive Patients With Malignant Diseases Indicating an HSCT
Official title: High-dose Chemotherapy With Transplantation of Gene-modified Haematopoietic Stem Cells for HIV-positive Patients With Malignant Diseases Indicating an HSCT
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: AIDS-related Lymphoma
HIV Infections
Keywords: AIDS
HIV
Lymphoma
Stem Cell Transplantation
gene-modified Stem Cells
treatment experienced
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
First posted: 2009-03-10
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Adverse events, ECOG performance status and laboratory safety tests
timeFrame: five years after transplantation
Secondary outcomes:
measure: Remission status (CR or PR)
timeFrame: five years after transplantation
measure: Any relapse of ARL
timeFrame: five years after transplantation
measure: level and kinetics of engraftment and level of gene marking
timeFrame: five years after transplantation
measure: Viral load
timeFrame: five years after transplantation
measure: CD4 counts
timeFrame: five years after transplantation
Other outcomes:
Locations:
city: Hamburg
country: Germany
facility: University Medical Center Hamburg-Eppendorf
Study officials:
affiliation: University Medical Center Hamburg-Eppendorf, Department for Stem Cell Transplantation
name: Nicolaus Kroeger
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yla-Herttuala S. Gene therapy moves forward in 2010. Mol Ther. 2011 Feb;19(2):219-20. doi: 10.1038/mt.2010.307. No abstract available.