Gene Therapy in Treating Patients With Human Immunodeficiency Virus-Related Lymphoma Receiving Stem Cell Transplant

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"Study looking at stem cell gene therapy to treat patients with HIV and lymphoma"
Age: 19 to 100 years old
Gender:
Any
Healthy Volunteers: No
Keywords: Non-Hodgkin's lymphoma, HIV infection, lymphoma, cancer, gene therapy, stem cell transplant, stem cell therapy
Type: Procedure study, Phase I/II
Investigator:
Description
This study is to test the safety of combining stem cell therapy with gene therapy to treat lymphoma. For gene therapy, researchers in a laboratory will add small stretches of DNA called “anti-HIV genes” into your stem cells to make the gene therapy product used in this study. The type of anti-HIV genes and therapy in this study might make your immune cells more resistant to HIV.
The goal of the study is to develop an immune system that can actively prevent new immune cells from getting infected with HIV, while the older cells die due to HIV. This new immune system might be able to fight the spread of HIV even without HIV medications.
The gene therapy product in combination with your clinically indicated stem cell transplant in this study is considered experimental because it has not been used in human clinical trials and has not been approved by the Food and Drug Administration (FDA) for treatment of HIV. A similar gene therapy product has been used in other human clinical trials with stem cell therapy.
This study requires

A review of your HIV status, which includes asking questions about behaviors related to risk factors for HIV, A physical examination, A chest x-ray, Pregnancy test for females who could become pregnant, An EKG (basic heart test), An echocardiogram (heart ultrasound) that assesses the heart function and heart valves, A pulmonary function test to determine how well your lungs are working and how well you are breathing, Blood tests (Approximately 4 tablespoons will be taken from a vein in your arm).You may be required to have: A cardiac stress test that assess heart function when you are exercising for about 20 minutes, An imaging scan of your body called CT scan or PET / CT Scan, to look at the location and size of your cancer and any possible source for infection, A bone scan if clinically indicated, and/or a bone marrow biopsy. Three part experimental stem cell therapy, with one-time infusion of stem cells with anti-HIV genes

Who can participate

Inclusion Criteria:

  • Inclusion criteria associated with type and status of lymphoma

  • Biopsy-proven intermediate or high-grade non-Hodgkin's lymphoma, meeting one of the following criteria (timeline 4 months prior to start of trial):

  • In partial remission

  • Relapsed after initial complete remission

  • Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease)

  • In complete remission with high-risk features as specified by the International Prognostic Index

  • Biopsy-proven advanced stage follicular lymphoma, that have failed at least two lines of therapy multi-agent chemotherapy, but responds to salvage therapy (i.e., chemosensitive disease) (timeline 4 months prior to start of trial)

  • Biopsy-proven advanced stage mantle cell lymphoma with proliferation-related Ki-67 antigen (Ki-67) > 10% in first complete remission (timeline 4 months prior to start of trial)

  • Biopsy-proven Hodgkin's lymphoma, meeting one of the following criteria (timeline 4 months prior to start of trial)

  • In first, or greater relapse after initial complete remission

  • In partial remission

  • Failed induction therapy, but responds to salvage therapy (i.e., chemosensitive disease)

  • Biopsy-proven Burkitt's lymphoma, meeting one of the following criteria (timeline 4 months prior to start of trial):

  • In second complete remission after relapse following initial complete remission,

  • Failed induction therapy, but responds (very good partial remission, complete remission, or near complete remission) to salvage therapy (i.e., chemosensitive disease)

  • Biopsy proven plasmablastic lymphomas, or peripheral T cell lymphoma (with the exception of anaplastic lymphoma kinase positive [ALK+] type in first or second complete remission) (timeline 4 months prior to start of trial)

  • INCLUSION CRITERIA ASSOCIATED WITH HIV-1 STATUS

  • HIV-1 infection, as documented by any federally approved, licensed HIV rapid test performed in conjunction with screening (or enzyme linked immunosorbent assay [ELISA], test kit, and confirmed by western blot or other approved test); alternatively, this documentation may include a record demonstrating that another physician has documented the participant's HIV status based on either: 1) approved diagnostic tests, or 2) the referring physician's written record that HIV infection was documented, with supporting information on the participant's relevant medical history and/or current management of HIV infection

  • Must be on a multi-drug anti-HIV regimen (excluding zidovudine [AZT, ZDV, Retrovir®, or agents containing zidovudine (e.g., Combivir® and Trizivir®)], and efavirenz [Sustiva®, or agents containing efavirenz (e.g., Atripla®)]), and have an HIV-1 viral load < 50 copies/mL by reverse transcriptase-polymerase chain reaction (RT-PCR) at the time of study enrollment; participants on zidovudine [AZT, ZDV, Retrovir®; including Combivir® and Trizivir®] and efavirenz [Sustiva®; including Atripla®] must switch to an alternative regimen without anticipated drug-drug interactions or myelosuppressive properties based on known viral resistance patterns and/or ART history, such as raltegravir and Truvada (emtricitabine and tenofovir) at least two weeks prior to the transplant

  • Participants with CD4 counts > 50/microL are eligible for this study if their viral load is < 50 copies/mL by reverse transcription polymerase chain reaction (RT-PCR) since majority of the participants have received aggressive chemotherapy that can potentially decrease the CD4 counts despite the ART therapy; timeline: within 3 weeks prior to start of trial

  • GENERAL INCLUSION CRITERIA (TIMELINE: 8 WEEKS PRIOR TO START OF TRIAL, UNLESS OTHERWISE SPECIFIED)

  • Karnofsky performance status of 70-100%; Eastern Cooperative Oncology Group (ECOG) performance status =< [2]

  • Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) >= 2.5 times upper limit of normal (ULN)

  • Serum bilirubin =< 2.5 times ULN except for participants who are on atazanavir or indinavir, provided that the participant's direct bilirubin is within normal institutional limits

  • Participants who are hepatitis C virus antibody positive, or hepatitis B virus surface antigen positive must be free of clinical evidence of cirrhosis as determined by the principal investigator in consultation with the gastroenterology service; timeline: within 3 weeks prior to start of trial

  • Participants with hepatitis B should be on appropriate anti-viral therapy at the time of the transplant, and their viral load should be under control; timeline: within 3 weeks prior to start of trial

  • Serum creatinine =< 2 times ULN; timeline: within 3 weeks prior to start of trial

  • Creatinine clearance >= 60 mL/min; timeline: within 3 weeks prior to start of trial

  • Prothrombin time (PT)/partial thromboplastin time (PTT) =< 2 times normal; timeline: within 3 weeks prior to start of trial

  • Forced expiratory volume in 1 second (FEV-1) or diffusion capacity of the lung for carbon monoxide (DLCO) >= 50% predicted; timeline: within 4 weeks prior to start of trial

  • Left ventricular ejection fraction (LVEF) >= 50% by 20-dimensional (20D) echocardiogram (ECHO) or multigated acquisition (MUGA) scan; timeline: within 4 weeks prior to start of trial

  • Not pregnant or nursing, with negative pregnancy test; timeline: within 3 weeks prior to start of trial

  • Life expectancy of greater than 3 months

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

  • Receipt of a stable ART regimen for at least 3 weeks prior to start of trial

Exclusion Criteria:

  • Participants with > 5% involvement of bone marrow by malignant cells (either by manual count or flow cytometry) prior to stem cell collection

  • Participants with any abnormal cytogenetics in the bone marrow not related to the lymphoma, and not deemed to be constitutional

  • Participants with unexplained anemia, and/or thrombocytopenia

  • Participants with clear evidence of myeloproliferative disorders, or myelodysplastic disorders in the marrow

  • Presence of any active central nervous system (CNS) disease at the time of evaluation (parenchymal or leptomeningeal)

  • Any history of HIV-1 associated encephalopathy

  • History of other acquired immune deficiency syndrome (AIDS)-related syndromes that are perceived to cause excessive risk for morbidity post-transplantation, as determined by the principal investigator

  • Symptomatic/active bacterial, or fungal, or any other opportunistic infection

  • Active cytomegalovirus (CMV) retinitis, or other active CMV-related organ dysfunction

  • Relapse of pneumocystis carinii pneumonia within the past year

  • Intractable, severe diarrhea, defined as > 1.500 cc diarrheal fluid per day, or diarrhea causing persistent severe electrolyte abnormalities, or hypoalbuminemia

  • History of active myocardial ischemia, cardiomyopathy, uncontrolled dysrhythmia, or congestive heart failure within the last 6 months before the evaluation

  • Dementia of any kind

  • Seizures within the past 12 months

  • History of grade III hemorrhagic cystitis due to prior cyclophosphamide chemotherapy

  • History of other prior malignancy, except squamous cell carcinoma of the cervix or anus, superficial basal cell or squamous cell skin cancer, or other malignancy curatively treated more than 5 years ago

  • Active psychosocial condition that would hinder study compliance and follow-up

  • Any perceived inability to directly (and without the means of a legal guardian) provide informed consent

  • Any medical or physical contraindication, or other inability to undergo hematopoietic progenitor cell (HPC) collection

  • Participants who are receiving any other investigational agents

  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

  • Pregnant women are excluded from this study; breastfeeding should be discontinued; these potential risks may also apply to other agents used in this study

Resources
Schedule
Study duration and period
Three part experimental stem cell therapy: variable Follow-up: Clinic visits, 2 years Long term follow-up: Phone/email once a year for 15 years+
Recruitment period
From March 16, 2016
Location
UC Davis Comprehensive Cancer Center
2279 45th Street
Sacramento, CA 95817
Research Topic
Conditions:
  • HIV Infection
  • Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma
  • Plasmablastic Lymphoma
  • Recurrent Adult Hodgkin Lymphoma
  • Recurrent Adult Non-Hodgkin Lymphoma
  • Recurrent Burkitt Lymphoma
  • Recurrent Follicular Lymphoma
  • Stage III Follicular Lymphoma
  • Stage III Mantle Cell Lymphoma
  • Stage IV Follicular Lymphoma
  • Stage IV Mantle Cell Lymphoma

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