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

NCT00858793 | Terminated Phase 1 DMC

• 1 other identifier: ARL-GT 2005
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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.

Conditions

AIDS-related Lymphoma; HIV Infections

Keywords

AIDS; HIV; Lymphoma; Stem Cell Transplantation; gene-modified Stem Cells; treatment experienced

Outcome Measures

Primary Outcomes (1)

• Adverse events, ECOG performance status and laboratory safety tests

  five years after transplantation

Secondary Outcomes (5)

• 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

Study Arms (1)

A

EXPERIMENTAL

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

Interventions

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

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.

A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead

Study Sites (1)

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Related Publications (1)

• 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.

  PMID: 21289631 RESULT

Related Links

• page 1435; abstract 109

MeSH Terms

Conditions

Lymphoma, AIDS-Related; HIV Infections; Acquired Immunodeficiency Syndrome; Lymphoma

Interventions

Genes

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Genome Components; Genome; Genetic Structures; Genetic Phenomena

Study Officials

• Nicolaus Kroeger

  University Medical Center Hamburg-Eppendorf, Department for Stem Cell Transplantation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2009
• First Posted: March 10, 2009
• Study Start: November 28, 2008
• Primary Completion: August 31, 2016
• Study Completion: August 31, 2016
• Last Updated: September 8, 2022

Record last verified: 2022-09

Locations

DE (1)