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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00858793
• Other study ID #: ARL-GT 2005
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 28, 2008
• Est. completion date: August 31, 2016

Study information

• Verified date: September 2022
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: August 31, 2016
• Est. primary completion date: August 31, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• AIDS-related Lymphoma
• HIV Infections
• Lymphoma, AIDS-Related

Intervention

Procedure:
• PBSC-M87o, Gene (M87o)-modified, CD34+ peripheral blood progenitor cells (PBSC)
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.

Locations

Country	Name	City	State
Germany	University Medical Center Hamburg-Eppendorf	Hamburg

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Ylä-Herttuala S. Gene therapy moves forward in 2010. Mol Ther. 2011 Feb;19(2):219-20. doi: 10.1038/mt.2010.307. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events, ECOG performance status and laboratory safety tests		five years after transplantation
Secondary	Remission status (CR or PR)		five years after transplantation
Secondary	Any relapse of ARL		five years after transplantation
Secondary	level and kinetics of engraftment and level of gene marking		five years after transplantation
Secondary	Viral load		five years after transplantation
Secondary	CD4 counts		five years after transplantation

External Links

•   page 1435; abstract 109