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

NCT01961063 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: 13282NCI-2013-01728
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (3)

• 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

  Up to 5 years

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

  First 28 days

• Time to platelet recovery to >= 50,000/uL

  First 90 days

Secondary Outcomes (6)

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

  Up to 5 years

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

  Up to 2 years

• Effect of ATI on HIV markers and CD4 count

  Up to 5 years

• Pharmacokinetic parameters of busulfan

  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

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

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

Study Arms (1)

Treatment (gene therapy)

EXPERIMENTAL

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

busulfan DRUG

Given IV

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

Treatment (gene therapy)

lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic progenitor cells BIOLOGICAL

Given IV

Also known as: lentivirus-transduced hematopoietic progenitor cells

Treatment (gene therapy)

pharmacological study OTHER

Correlative studies

Treatment (gene therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (gene therapy)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Busulfan

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Amrita Krishnan

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2013
• First Posted: October 11, 2013
• Study Start: December 31, 2015
• Primary Completion (Estimated): August 5, 2026
• Study Completion (Estimated): August 5, 2026
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

US (1)