Gene-Modified HIV-Protected Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma

PRIMARY OBJECTIVES:

I. To assess the safety and feasibility of infusing gene-modified, HIV-protected
hematopoietic stem/progenitor cells (HSPC) after high-dose chemotherapy for treatment of
acquired immune deficiency syndrome (AIDS)-related lymphoma.

II. To observe the change in gene-modified cell levels before and after antiviral treatment
interruption.

SECONDARY OBJECTIVES:

I. To evaluate the molecular and clonal composition of gene-modified cells after
hematopoietic cell transplant (HCT).

II. To describe time to disease progression, progression-free survival, treatment-related
mortality, time to neutrophil and platelet recovery, and incidence of infections.

TERTIARY OBJECTIVES:

I. To evaluate the effect of procedure on HIV-specific immune reconstitution.

II. To observe the effect of HIV infection on the presence of gene-marked cells as determined
by deoxyribonucleic (DNA) polymerase chain reaction (PCR).

OUTLINE:

CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to
institutional guidelines.

STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant with LVsh5/C46
(Cal-1) transduced autologous CD34+ hematopoietic stem/progenitor cells (HSPC) on day 0.

Note: Patients continue to receive highly active antiretroviral therapy (HAART) throughout
treatment, with a 7-day break for apheresis. Patients may be eligible for a structured
treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant
with gene-modified cells.

After completion of study treatment, patients are followed up periodically for 2 years, every
6 months for 3 years, and then annually for 15 years post-HCT.

Inclusion Criteria:

- HIV-1 seropositive

- Stable, continuous antiretroviral treatment for at least three months before
enrollment, defined as a multi-drug regimen (excluding azidothymidine [AZT])

- HIV plasma viral load < 50 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 or first partial remission or induction
failure with subsequent response to salvage therapy

- Non-Hodgkin's lymphoma beyond first remission or first partial remission or
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 enrollment

- Subjects must be on a prophylactic regimen for pneumocystis carinii pneumonia, or
agree to begin such treatment, if CD4+ cell counts are observed to be =< 200/ul in
peripheral blood

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Renal disease: serum creatinine > 2 times upper limit of normal

- Liver disease: 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

- Serum bilirubin greater than 3 times the upper limit of normal, unless attributed to
Gilbert's syndrome

- Pulmonary disease: forced vital capacity (FVC) < 60% predicted

- Pulmonary disease: forced expiratory volume in 1 second (FEV1) < 60% predicted

- Pulmonary disease: diffusion capacity of the lung for carbon monoxide (DLCO)
parameters < 60% predicted (corrected for hemoglobin)

- Cardiac insufficiency: 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)

- Hepatitis B surface antigen positive

- Hepatitis C virus (HCV) antibody positive and detectable HCV quantitative ribonucleic
acid (RNA) with clinical evidence of cirrhosis

- Requiring active treatment for Toxoplasma gondii

- Planned radiation therapy after transplant

- 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 HAART or medical therapy

- Any concurrent or past medical condition that, in the opinion of the Investigator,
would exclude the subject from participation or any psychosocial conditions that would
hinder study compliance or follow-up, at the discretion of the Investigator

- Receipt of a vaccine for HIV-1 or any prior gene modified cell product, at any time

- Known hypersensitivity to any of the products used in the trial-G-CSF (Neupogen),
plerixafor, or any planned components of conditioning regimens

- Pregnant or nursing women