This study is NOT currently recruiting participants.
Number
15-C-0078
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: No longer recruiting/follow-up only Gender: Male & Female Min Age: 18 Max Age: 65
Referral Letter Required
No
Population Exclusion(s)
Pregnant Women;Fetuses;Children
Keywords
Gene Therapy for HIV; Multiplexed RNA-Based Anti-HIV Gene Transfer; Chemo and Gene Therapy for HIV Lymphoma; Analytic HIV Antiviral Treatment Interruption
Recruitment Keyword(s)
None
Condition(s)
AIDS-related lymphoma; Large B-Cell, Diffuse Lymphoma; Plasmablastic Lymphoma
Investigational Drug(s)
Lentivirus vector rHIV7-shI-TAR-CCR5RZ
Investigational Device(s)
Intervention(s)
Biological/Vaccine: Lentivirus vector rHIV7-shI-TAR-CCR5RZ Drug: R-EPOCH
Supporting Site
National Cancer InstituteCity of Hope Medical Center
- Some genes can slow HIV, the virus that causes AIDS. Researchers want to put three of these genes into peoples blood stem cells. Any new blood cells would have the three genes and could be protected from HIV.
Objectives:
- To find more long-term positive results in treating HIV and lymphoma.
Eligibility:
- Adults 18 65 with diffuse large B cell lymphoma and HIV.
Design:
- Participants will be screened with medical history, physical exam, spinal tap, and blood tests. They may have a biopsy and CT scan.
- Participants will have an intravenous (IV) catheter placed in a large vein.
- Participants will have up to six 21-day cycles:
-- They will get chemotherapy drugs by IV over 5 days. They will get other drugs for side effects.
-- Another drug will be injected under their skin until their white blood cell counts reach a certain level.
- Participants will have a PET scan after cycle 3.
- Some participants will have anti-HIV gene therapy:
-- After cycle 4, they will take a drug to increase stem cells. Blood will be taken. A machine will remove stem cells. The rest of the blood will be returned.
-- The stem cells genes will be modified. Participants whose genes are determined as safe will get the cells injected after cycle 6.
-- These participants will stop taking antiretroviral therapy (ART) for up to 16 weeks. They will have 11 blood draws and phone check-ups for 16 weeks.
- Stem cell participants will have follow-up visits for up to 15 years.
- Other participants will have 10 follow-up visits over 2 years.
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INCLUSION CRITERIA: - Age greater than or equal to 18 years and less than or equal to 65 years. - HIV seropositive at or before the time of lymphoma diagnosis. All HIV positive patients are eligible regardless of HIV viral load or antiretroviral therapy (ART) status. All patients on study will receive ART as per standard guidelines. - ECOG performance status 0 - 2. - Biopsy proven lymphoma for which R-EPOCH is appropriate frontline therapy, e.g., Burkitt Lymphoma or DLBCL NHL, including plasmablastic lymphoma and primary effusion lymphoma but not T-cell lymphoma. Tissue histology will be reviewed at the treating institution. - No psychosocial conditions that would hinder study compliance and follow-up. - Pretreatment SGOT, SGPT and serum bilirubin, less than or equal to 2.5x institutional upper limit of normal (ULN) or total bilirubin <4.5mg/dl with direct fraction less than or equal to 0.3mg/dl in patients for whom these abnormalities are felt to be due to protease inhibitor therapy. - Patients with evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection must have no clinical evidence of cirrhosis. - Serum creatinine < 2x the institutional ULN; however, if serum creatinine >1.5x ULN, a 24 hour urine creatinine clearance must be >50 ml/min unless there is renal involvement by lymphoma. - Absence of clinically significant cardiomyopathy, congestive heart failure. - If the subject is female and of child bearing potential, subject must have negative serum or urine pregnancy test within 7 days of treatment with research agent. Men with partners of child-bearing potential and women of child-bearing potential must be willing to use medically effective birth control methods, e.g. contraceptive pill, condom, or diaphragm and continue this for one year post HSPC infusion. - Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment and remain on treatment until after completion of therapy and until the CD4 cells are greater than 200/mm3. EXCLUSION CRITERIA: - Any AIDS-related opportunistic infection occurring within the past year and for which treatment has been unsuccessful would be considered exclusionary, but this is done on a case-by-case basis as determined by the Principal Investigator (PI). - Active CMV retinitis or other active CMV-related organ dysfunction. Patients with a history of treated CMV infection are not excluded. - AIDS-related syndromes, infectious or otherwise, if perceived to cause excessive risk for morbidity post-HSPC infusion, as determined by the PI. Examples include, but are not limited to: Severe AIDS-related wasting Severe intractable diarrhea Active inadequately treated opportunistic infection of the CNS Primary CNS Lymphoma - Pregnant or nursing women. - Any 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]. - Any medical or physical contraindication or other inability to undergo HSPC collection - Patients should not have any uncontrolled illness including ongoing or active infection other than HIV. - Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to G-CSF/filgrastim (E. coli producing cell line) and plerixafor. - Patients with other active malignancies. However, patients with skin cancers, namely basal cell or squamous cell carcinoma, and malignancies treated with curative intent having no known active disease present for greater than or equal to 2 years, may be eligible.
- Age greater than or equal to 18 years and less than or equal to 65 years.
- HIV seropositive at or before the time of lymphoma diagnosis. All HIV positive patients are eligible regardless of HIV viral load or antiretroviral therapy (ART) status. All patients on study will receive ART as per standard guidelines.
- ECOG performance status 0 - 2.
- Biopsy proven lymphoma for which R-EPOCH is appropriate frontline therapy, e.g., Burkitt Lymphoma or DLBCL NHL, including plasmablastic lymphoma and primary effusion lymphoma but not T-cell lymphoma. Tissue histology will be reviewed at the treating institution.
- No psychosocial conditions that would hinder study compliance and follow-up.
- Pretreatment SGOT, SGPT and serum bilirubin, less than or equal to 2.5x institutional upper limit of normal (ULN) or total bilirubin <4.5mg/dl with direct fraction less than or equal to 0.3mg/dl in patients for whom these abnormalities are felt to be due to protease inhibitor therapy.
- Patients with evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection must have no clinical evidence of cirrhosis.
- Serum creatinine < 2x the institutional ULN; however, if serum creatinine >1.5x ULN, a 24 hour urine creatinine clearance must be >50 ml/min unless there is renal involvement by lymphoma.
- Absence of clinically significant cardiomyopathy, congestive heart failure.
- If the subject is female and of child bearing potential, subject must have negative serum or urine pregnancy test within 7 days of treatment with research agent. Men with partners of child-bearing potential and women of child-bearing potential must be willing to use medically effective birth control methods, e.g. contraceptive pill, condom, or diaphragm and continue this for one year post HSPC infusion.
- Subjects must be on a prophylactic regimen for Pneumocystis carinii pneumonia, or agree to begin such treatment and remain on treatment until after completion of therapy and until the CD4 cells are greater than 200/mm3.
EXCLUSION CRITERIA:
- Any AIDS-related opportunistic infection occurring within the past year and for which treatment has been unsuccessful would be considered exclusionary, but this is done on a case-by-case basis as determined by the Principal Investigator (PI).
- Active CMV retinitis or other active CMV-related organ dysfunction. Patients with a history of treated CMV infection are not excluded.
- AIDS-related syndromes, infectious or otherwise, if perceived to cause excessive risk for morbidity post-HSPC infusion, as determined by the PI. Examples include, but are not limited to:
Severe AIDS-related wasting
Severe intractable diarrhea
Active inadequately treated opportunistic infection of the CNS
Primary CNS Lymphoma
- Pregnant or nursing women.
- Any 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].
- Any medical or physical contraindication or other inability to undergo HSPC collection
- Patients should not have any uncontrolled illness including ongoing or active infection other than HIV.
- Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to G-CSF/filgrastim (E. coli producing cell line) and plerixafor.
- Patients with other active malignancies. However, patients with skin cancers, namely basal cell or squamous cell carcinoma, and malignancies treated with curative intent having no known active disease present for greater than or equal to 2 years, may be eligible.
Principal Investigator
Referral Contact
For more information: