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

Purpose

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


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Genes and Gene Therapy HIV/AIDS Lymphoma

Genetic and Rare Diseases Information Center resources: Lymphosarcoma Primary Effusion Lymphoma Lymphoma AIDS Related B-cell Lymphoma

U.S. FDA Resources

Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:

Adverse events, ECOG performance status and laboratory safety tests [ Time Frame: five years after transplantation ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]


Estimated Enrollment:	10
Study Start Date:	October 2008
Estimated Study Completion Date:	October 2017
Estimated Primary Completion Date:	December 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00858793

Locations


Germany
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf

Investigators


Principal Investigator:	Nicolaus Kroeger	University Medical Center Hamburg-Eppendorf, Department for Stem Cell Transplantation

More Information


Responsible Party:	Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:	NCT00858793 History of Changes
Other Study ID Numbers:	ARL-GT 2005
Study First Received:	March 9, 2009
Last Updated:	May 12, 2015
Health Authority:	Germany: Paul-Ehrlich-Institut

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:


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

Additional relevant MeSH terms:


HIV Infections HIV Seropositivity Lymphoma, AIDS-Related Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes	Immune System Diseases Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders

ClinicalTrials.gov processed this record on September 28, 2016