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Active, not recruitingNCT01961063Updated Sep 1, 2026

Gene Therapy After Frontline Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

A Phase 1 interventional study of busulfan and lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells in AIDS-related Non-Hodgkin Lymphoma, AIDS-related Plasmablastic Lymphoma and AIDS-related Primary Effusion Lymphoma, sponsored by City of Hope Medical Center. Active, not recruiting at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-01.

Sponsored by City of Hope Medical Center · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
3
Allocation
Not applicable
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This pilot clinical trial studies gene therapy after frontline chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL). Placing genes for anti-human immunodeficiency virus (HIV) ribonucleic acid (RNA) into stem/progenitor cells may make the body build an immune response to AIDS. Giving the chemotherapy drug busulfan before gene therapy can help gene-modified cells engraft and work better.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate the safety and feasibility of recombinant (r)HIV7-short hairpin RNA targeted to the HIV-1 tat/rev (shI)-trans-active response element (TAR)-chemokine cysteine-cysteine receptor 5 ribozyme (CCR5RZ)-treated hematopoietic stem progenitor cells (HSPC) (lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells) infusion in AIDS patients completing treatment for NHL and non-myeloablative conditioning with busulfan.

II. To demonstrate the engraftment of gene-modified progeny cells following such treatment.

III. To determine if selection of these gene-modified progeny cells occurs during analytical treatment interruption (ATI) of combination anti-retroviral therapy (cART).

SECONDARY OBJECTIVES:

I. To evaluate the pharmacokinetics of busulfan in patients with AIDS-related lymphoma (ARL).

II. To determine the effects of HIV-1 infection on the presence of gene-marked peripheral blood mononuclear cells (PBMC) as measured by woodchuck post-transcriptional regulatory element (WPRE) deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) performed before, during, and after ATI.

OUTLINE: Patients receive busulfan intravenously (IV) over 3 hours on day -2 followed by lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells IV on day 0.

After completion of study treatment, patients are followed up at 1, 7, 14, and 21 days and 1, 2, 3, 6, 9, 12, 18, and 24 months and then annually for 3 years.

02

Conditions studied

  • AIDS-related Non-Hodgkin Lymphoma
  • AIDS-related Plasmablastic Lymphoma
  • AIDS-related Primary Effusion Lymphoma
  • HIV Infection

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03

In context

HIV Infections

4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's planned enrollment of 3 is below the median of 83 across 3,251 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

City of Hope Medical Center is the lead sponsor of 670 studies on the registry; 181 are open to participants now.

Of its 30 completed or terminated interventional studies of FDA-regulated products, 12 (40%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • HIV-1 seropositive at or before the time of lymphoma diagnosis
  • Karnofsky performance status >= 70%
  • Biopsy proven NHL, including plasmablastic lymphoma and primary effusion lymphoma but not T-cell lymphoma; tissue histology will be reviewed at City of Hope (COH); patients who have been in remission for > 1 year post Hodgkin's lymphoma chemotherapy are also considered eligible
  • >= 28 days from completion of frontline chemotherapy for NHL
  • If remission status \< 1 year for NHL, complete remission documented by computed tomography (CT) or positron emission tomography (PET)-CT scan within 3 months of study entry
  • No diagnosed psychosocial conditions that would hinder study compliance and follow-up
  • Pretreatment serum glutamic oxaloacetic transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) =\< 2.5 x institutional upper limit of normal (ULN)
  • Pretreatment serum bilirubin =\< 2.5 x institutional ULN or - Total bilirubin \< 4.5 mg/dl with direct fraction =\< 0.3 mg/dl in patients for whom these abnormalities are felt to be due to protease inhibitor therapy
  • Serum creatinine \< 2 x the institutional ULN
  • Absence of clinically significant cardiomyopathy, congestive heart failure
  • Cardiac ejection fraction has to be >= 50%
  • Spirometry diffusion capacity (diffusion capacity of the lung for carbon monoxide [DLCO]) >= 50%
  • 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, if the cluster of differentiation (CD)4 counts are \< 200 cells/uL

SECONDARY ELIGIBILITY CRITERIA FOR GENE-MODIFIED HSPC INFUSION:

  • Subjects must complete the filgrastim (G-CSF)/plerixafor mobilization of peripheral blood progenitor cells and must have collected at least 7.5 x 10\^6 CD34+ cells/kg, sufficient for preparation of both, a back-up of 2.5 x 10\^6 CD34+ cells and the research product
  • Research product must pass all release tests
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
  • All subjects must have the ability to understand and the willingness to sign a written informed consent

Exclusion criteria

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
  • Active cytomegalovirus (CMV) retinitis or other active CMV-related organ dysfunction; patients with a history of treated CMV infection are not excluded
  • Patients who are hepatitis C virus (HCV) antibody positive and HCV ribonucleic acid (RNA) or hepatitis B virus (HBV) surface antigen positive and HBV DNA positive
  • Pregnant or nursing women
  • Active central nervous system (CNS) lymphoma, history of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months; patients with a history of positive cerebrospinal fluid cytology that has become negative with intrathecal chemotherapy and the patient has been in remission for at least 12 months are eligible
  • Any history of HIV-1 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 any other inability to undergo HSPC collection
  • Patients should not have any uncontrolled illness including ongoing or active infection
  • 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 (Escherichia [E] coli producing cell line), plerixafor or busulfan
  • Patients with other active malignancies other than skin cancers are ineligible for this study
  • Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study will be considered non-compliant
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
3 participants (estimated)

Study arms

  • Experimental
    Treatment (gene therapy)

    Patients receive busulfan IV over 3 hours on day -2 followed by lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells IV on day 0.

    Drug: busulfan · Biological: lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells · Other: pharmacological study · Other: laboratory biomarker analysis

Interventions

  • Drugbusulfan

    Given IV

    Also known as: BSF, BU, Misulfan, Mitosan, Myeloleukon

  • Biologicallentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells

    Given IV

    Also known as: lentivirus-transduced hematopoietic progenitor cells

  • Otherpharmacological study

    Correlative studies

  • Otherlaboratory biomarker analysis

    Correlative studies

06

What researchers measure

Primary outcomes

  1. Procedure related toxicity as determined by adverse events (AE) grading scale using the Common Terminology Criteria for Adverse Events (CTCAE) version v4.03

    Tables will be created to summarize these toxicities and side effects by dose

    Time frame: Up to 5 years

  2. Time to Absolute Neutrophil Count (ANC) >= 500/uL

    Time frame: First 28 days

  3. Time to platelet recovery to >= 50,000/uL

    Time frame: First 90 days

Secondary outcomes

  1. Evidence for and duration of vector-marked PBMC/marrow cells assessed by PCR

    PCR-based assay on PBMC

    Time frame: Up to 5 years

  2. Expression of the RNA transgenes in lineage-specific progeny of the transduced cells assessed by PCR

    PCR-based assay on FACS-sorted cells

    Time frame: Up to 2 years

  3. Effect of ATI on HIV markers and CD4 count

    HIV proviral DNA, HIV RNA single copy, and 2-LTR circle DNA from PBMCs

    Time frame: Up to 5 years

  4. Pharmacokinetic parameters of busulfan

    Cmax, CLsys, Vd, t1/2's, AUC

    Time frame: Day -2 at 0 hours (pre-infusion); 3 hours (just before end of infusion); and at 4, 5, and 6 hours and day -1 at 24 hours

  5. Ability to obtain suitable numbers of transduced HSPC for engraftment assessed by FACS

    The number and type of cells will be determined by fluorescence activated cell sorting (FACS) analysis of the final cell product. The minimum target number of CD34+ cells for collection is 7.5 x 10e6 cells/kg and, in the final transduced cell product, the number of CD34+ cells must be \>= 2.0 x 10e6 CD34+ cells/kg with total viability \>= 70%.

    Time frame: Up to day -2 (Pre-infusion of the investigational drug)

  6. Feasibility of product manufacturing as evidenced by product release assessed by release assays

    Release assays

    Time frame: Up to day -2 (Pre-infusion of the investigational drug)

07

Study locations

1 site
  • City of Hope Medical Center
    Duarte, California 91010, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 1, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT01961063
Lead sponsor
City of Hope Medical Center
Responsible party
Sponsor
First posted
Oct 11, 2013
Start date
Dec 31, 2015
Primary completion
Jul 6, 2027 (estimated)
Completion
Jul 6, 2027 (estimated)
Last update
Sep 1, 2026

Study contacts

Amrita Krishnan
principal investigator · City of Hope Medical Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.

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