Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma
AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA
3 other identifiers
interventional
N/A
1 country
1
Brief Summary
This clinical trial studies genetically modified peripheral blood stem cell transplant in treating patients with HIV-associated non-Hodgkin or Hodgkin lymphoma. Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. Laboratory-treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy
Trial Health
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Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 15, 2013
CompletedFirst Posted
Study publicly available on registry
January 17, 2013
CompletedStudy Start
First participant enrolled
February 1, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2019
CompletedMay 7, 2015
May 1, 2015
4 years
January 15, 2013
May 6, 2015
Conditions
Outcome Measures
Primary Outcomes (6)
Safety of infusion of gene-modified cells, measured by grade 3 or greater toxicities related to infusion of gene-modified cells using the Common Toxicity Criteria version 4.0(CTCv.4)
Up to day 180
Safety of O6BG/BCNU in vivo selection, defined as less than 25% of patients developing grade 3 or greater non-hematopoietic toxicity or grade 4 CTCv.4 hematopoietic toxicity
Up to day 180
Safety of structured treatment interruption defined as no decline in CD4 count by more than 25%, no HIV RNA more than 10,000 copies/mL; and no elevation of immune activation markers
During the 12 weeks without HAART
Efficacy of gene transduction, defined as collection of more than 4.5 x 10^6 CD34+ cells/kg cells for genetic modification and evidence of gene-marked cells before HSC infusion
Up to 3 months
Efficacy of infusion of gene-modified cells, defined as engraftment of at least1% gene-modified cells
Up to 3 months
Efficacy of O6BG/BCNU in vivo selection, defined as selection of gene-modified cells to a level at least 10% of peripheral blood cells
Up to 3 months
Study Arms (1)
Treatment (gene modified peripheral blood cell transplant)
EXPERIMENTALCONDITIONING: Patients receive carmustine IV over 3 hours on day -7, cytarabine IV over 2 hours BID and etoposide IV over 2 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. TRANSPLANTATION: Patients receive an autologous PBSC infusion and/or infusion of autologous transduced hematopoietic cells on day 0. Beginning 28-120 days later, patients eligible for in vivo selection after detection of gene-marked cells receive O6-benzylguanine IV over 1 hour and carmustine IV over 3 hours on days 14, 28, and then monthly until completion of therapy. Patients achieving \> 10% gene marking and CD4 count of \>= 500 cells/uL receive up to 2 courses of structured treatment interruption without undergoing in vivo selection.
Interventions
Given IV
Given IV
Given IV
Given IV
Given IV
Undergo transduced and/or non-transduced transplant
Undergo transduced and/or non-transduced transplant
Correlative studies
Eligibility Criteria
You may qualify if:
- HIV seropositive
- Antiretroviral treatment for at least one month, defined as a multi-drug regimen (excluding azacitidine \[AZT\])
- HIV plasma viral load has decreased by 1.5 logs or viral load \< 5000 copies/ml
- Non-Hodgkin or Hodgkin lymphoma without active central nervous system (CNS) involvement associated with poor prognosis with medical therapy alone or for which autologous peripheral blood stem cell (PBSC) transplant is indicated:
- Hodgkin's lymphoma beyond first remission; first partial remission; induction failure with subsequent response to salvage therapy
- Non-Hodgkin's Lymphoma beyond first remission: first partial remission; induction failure with subsequent response to salvage therapy
- Chemotherapy responsive disease
- Karnofsky performance score \>= 70%
- Subjects must agree to use effective contraception from enrollment through completion of the study
- Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of treatment
- Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment, if the cluster of differentiation (CD)4 counts are =\< 200
- Ability to understand and the willingness to sign a written informed consent document
You may not qualify if:
- Serum creatinine \> 2 times upper limit of normal
- Serum bilirubin greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy or attributed to Gilbert's syndrome
- Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) or diffusion capacity of the lung of carbon monoxide (DLCO) parameters \< 60% predicted (corrected for hemoglobin)
- Left ventricular ejection fraction (LVEF) \< 50% or coronary artery disease requiring treatment
- Active infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
- Patients who are hepatitis C virus (HCV) antibody positive or hepatitis B virus (HBV) surface antigen positive must be free of clinical evidence of cirrhosis that would otherwise make them ineligible for HCT, as determined by the Principal Investigator (P.I.) in consultation with the Gastrointestinal Service; patients with HBV and ongoing evidence of viral replication may require therapy prior to receiving high-dose chemotherapy
- Positive serology for Toxoplasma gondii AND requiring treatment or with evidence of active infection
- Malignancy other than lymphoma, unless 1) in complete remission and more than 5 years from last treatment), or 2) cervical/anal squamous cell carcinoma in situ or 3) superficial basal cell and squamous cell cancers of the skin
- History of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; any perceived inability to directly provide informed consent (Note: Consent may not be obtained by means of a legal guardian)
- A medical history of noncompliance with highly active anti-retroviral therapy (HAART) or medical therapy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Ann Woolfrey
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 15, 2013
First Posted
January 17, 2013
Study Start
February 1, 2015
Primary Completion
February 1, 2019
Last Updated
May 7, 2015
Record last verified: 2015-05