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AzTrials

AIDS-related Non-Hodgkin LymphomaPhase 1NCT01961063

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

A Phase 1 study testing busulfan, lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells and pharmacological study in people with AIDS-related Non-Hodgkin Lymphoma and AIDS-related Plasmablastic Lymphoma, run by City of Hope Medical Center at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
busulfan, lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells and pharmacological study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
31 Dec 2015to 6 Jul 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • City of Hope Medical Center

    Duarte, California, 91010

Other trials in United States

About this study

Official title: Safety and Feasibility of Gene Transfer After Frontline Chemotherapy for Non-Hodgkin Lymphoma in AIDS Patients Using Peripheral Blood Stem/Progenitor Cells Treated With a Lentivirus Vector-Encoding Multiple Anti-HIV RNAs

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:

  1. 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:

  1. 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.

Being tested
busulfan, lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells, pharmacological study, laboratory biomarker analysis
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • busulfanDrug

    Also called BSF, BU, Misulfan, Mitosan

    Given IV

  • lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cellsBiological

    Also called lentivirus-transduced hematopoietic progenitor cells

    Given IV

  • pharmacological studyOther

    Correlative studies

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01961063
Study groupRoleWhat they receive
Treatment (gene therapy)ExperimentalPatients 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.
Receives: Drug: busulfan; Biological: lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells; Other: pharmacological study; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: Up to 5 years

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

    Measured: First 28 days

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

    Measured: First 90 days

Secondary outcomes (6)

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

    PCR-based assay on PBMC

    Measured: 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

    Measured: 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

    Measured: Up to 5 years

  4. Pharmacokinetic parameters of busulfan

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

    Measured: 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%.

    Measured: 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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Oct 2013 (estimated)
  2. Study start31 Dec 2015
  3. Primary completion6 Jul 2027 (estimated)
  4. Study completion6 Jul 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01961063
Sponsor's protocol ID
13282
Other IDs
NCI-2013-01728, 13282
Status last verified
Aug 2026
First submitted
9 Sep 2013
Last updated
1 Sep 2026
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing busulfan, lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells and pharmacological study in people with AIDS-related Non-Hodgkin Lymphoma and AIDS-related Plasmablastic Lymphoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Procedure related toxicity as determined by adverse events (AE) grading scale using the Common Terminology Criteria for Adverse Events (CTCAE) version v4.03 (time frame: Up to 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01961063.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.

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