Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

Trial Information

AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of infusing gene-modified, human immunodeficiency
virus (HIV)-protected hematopoietic stem cells (HSC) after high-dose chemotherapy for
treatment of acquired immunodeficiency syndrome (AIDS)-related lymphoma.

II. To determine the dose of carmustine (BCNU) in combination with O^6-benzylguanine (O6BG)
that results in selection in vivo of gene-modified HIV-resistant cells.

III. To estimate the effect of HIV infection on the presence of HIV-resistant blood cells as
measured by genetic marking for vector sequences before and after antiviral treatment
interruption.

SECONDARY OBJECTIVES:

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

II. Evaluate the molecular and clonal composition of gene-modified cells after O6BG/BCNU.

III. Determine the correlation of the level of O6-methylguanine- methyltransferase (MGMT)
(P140K) marking with toxicity and response.

IV. Characterize the toxicity associated with in vivo selection. V. Determine the efficacy
of the procedure for treatment of lymphoma: defined as time to disease progression,
progression-free survival, treatment-related mortality, time to neutrophil and platelet
recovery, and incidence of infections.

TERTIARY OBJECTIVES:

I. Effect of procedure on the latent HIV reservoir. II. Effect of procedure on HIV-specific
immune reconstitution.

OUTLINE:

CONDITIONING: Patients receive carmustine intravenously (IV) over 3 hours on day -7,
cytarabine IV over 2 hours twice daily (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.

After completion of study treatment, patients are followed up periodically for 15 years.

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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)

Outcome Time Frame:

Up to day 180

Safety Issue:

Yes

Principal Investigator

Ann Woolfrey

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Authority:

United States: Federal Government

Study ID:

2583.00

NCT ID:

NCT01769911

Start Date:

February 2013

Completion Date:

Related Keywords:

Adult Nasal Type Extranodal NK/T-cell Lymphoma
AIDS-related Diffuse Large Cell Lymphoma
AIDS-related Diffuse Mixed Cell Lymphoma
AIDS-related Diffuse Small Cleaved Cell Lymphoma
AIDS-related Immunoblastic Large Cell Lymphoma
AIDS-related Lymphoblastic Lymphoma
AIDS-related Peripheral/Systemic Lymphoma
AIDS-related Small Noncleaved Cell Lymphoma
Anaplastic Large Cell Lymphoma
Angioimmunoblastic T-cell Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Hepatosplenic T-cell Lymphoma
HIV-associated Hodgkin Lymphoma
Intraocular Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Noncutaneous Extranodal Lymphoma
Peripheral T-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Hodgkin Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Adult T-cell Leukemia/Lymphoma
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Marginal Zone Lymphoma
Recurrent Mycosis Fungoides/Sezary Syndrome
Recurrent Small Lymphocytic Lymphoma
Refractory Hairy Cell Leukemia
Small Intestine Lymphoma
Splenic Marginal Zone Lymphoma
Stage I AIDS-related Lymphoma
Stage II AIDS-related Lymphoma
Stage III AIDS-related Lymphoma
Stage IV AIDS-related Lymphoma
T-cell Large Granular Lymphocyte Leukemia
Testicular Lymphoma
Waldenström Macroglobulinemia
Acquired Immunodeficiency Syndrome
HIV Infections
Burkitt Lymphoma
Hodgkin Disease
Immunoblastic Lymphadenopathy
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Hairy Cell
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, T-Cell, Peripheral
Lymphoma, AIDS-Related
Lymphoma, Large-Cell, Anaplastic
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Leukemia, Large Granular Lymphocytic

Name	Location
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle, Washington 98109

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Trial Information

Inclusion Criteria:

Type of Study:

Study Design:

Outcome Measure:

Outcome Time Frame:

Safety Issue:

Principal Investigator

Investigator Role:

Investigator Affiliation:

Authority:

Study ID:

NCT ID:

Start Date:

Completion Date:

Related Keywords:

Name

Location