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

Sponsor

Universitätsklinikum Hamburg-Eppendorf (Other)

Overall Status

Completed

CT.gov ID

NCT00858793

Collaborator

(none)

Enrollment

Location

Arm

93.1

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
AIDS-related Lymphoma HIV Infections	Procedure: PBSC-M87o, Gene (M87o)-modified, CD34+ peripheral blood progenitor cells (PBSC)	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

5 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 28, 2008

Actual Primary Completion Date :

Aug 31, 2016

Actual Study Completion Date :

Aug 31, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	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.

Arm

Intervention/Treatment

Experimental: A

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

Outcome Measures

Primary Outcome Measures

Adverse events, ECOG performance status and laboratory safety tests [five years after transplantation]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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