Gene Therapy and Combination Chemotherapy in Treating Patients With AIDS-Related Non-Hodgkin Lymphoma

NCT02337985 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: 14004NCI-2014-02416U01CA183012
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies gene therapy following combination chemotherapy in treating patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma. Placing genes that have been shown in the laboratory to inhibit the growth and spread of the immunodeficiency virus (HIV) into the patient's peripheral blood stem cells may improve the body's ability to fight HIV. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving gene therapy after combination chemotherapy may improve the body's ability to fight HIV and AIDS-related non-Hodgkin lymphoma.

Conditions

AIDS-Related Burkitt Lymphoma; AIDS-Related Diffuse Large B-cell Lymphoma; AIDS-Related Plasmablastic Lymphoma; AIDS-Related Primary Effusion Lymphoma; HIV Infection; AIDS Related Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events related to R-EPOCH, graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03

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

  Up to 2 years after completion of treatment

• Incidence of adverse events related to lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic stem/progenitor cells infusion, graded using the NCI CTCAE version 4.03

  All toxicities, related and unrelated, observed after each stem cell infusion will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity (by NCI CTCAE and nadir or maximum values for the laboratory measures), time of onset (i.e. course number), duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and by course.

  Up to 2 years

• Ability to obtain suitable numbers of lentiviral vector treated HSPC as determined by cell count

  Up to day -2 (pre-infusion)

• Presence of transgene in peripheral blood by digital droplet PCR

  Up to 2 years

Secondary Outcomes (5)

• Transgene ribonucleic acid expression by Northern blotting/hybridization and quantitative real-time PCR assay

  Up to 15 years

• HIV reservoir as determined by HIV-1 reverse transcriptase (RT)-PCR, DNA PCR, and DNA 2 long terminal repeat circle PCR

  Up to 15 years and during ATI

• HIV integration analysis by number of reads and loci

  Up to 15 years

• Vector transgene sequences in peripheral blood mononuclear cells

  Up to 2 years, possibly up to 15 years

• Change in of shI-TAR-CCR5RZ-marked cells in bone marrow

  Baseline to up to 18 months

Study Arms (1)

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

EXPERIMENTAL

Patients receive prednisone PO BID on days 1-5; rituximab IV on day 1; etoposide IV over 96 hours, doxorubicin hydrochloride IV over 96 hours and vincristine sulfate IV over 96 hours on days 1-4; and cyclophosphamide IV over 30-60 minutes on day 5. Patients then receive filgrastim SC QD beginning on day 6 and continuing until absolute neutrophil count recovers. Treatment repeats every 21 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive lentivirus vector rHIV7-shI-TAR-CCR5RZ-transduced hematopoietic stem/progenitor cells IV on day 0 (48 hours after the final combination chemotherapy course.)

Drug: Prednisone; Biological: Rituximab; Drug: Etoposide; Drug: Doxorubicin Hydrochloride; Drug: Vincristine Sulfate; Drug: Cyclophosphamide; Biological: Filgrastim; Biological: Lentivirus Vector rHIV7-shI-TAR-CCR5RZ-transduced Hematopoietic Stem/Progenitor Cells

Interventions

Prednisone DRUG

Given PO

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

Rituximab BIOLOGICAL

Given IV

Also known as: MOAB IDEC-C2B8

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

Etoposide DRUG

Given IV

Also known as: Lastet, VP 16

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: Adriamycin

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Oncovin, VCR, Vincasar

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

Cyclophosphamide DRUG

Given IV

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

Filgrastim BIOLOGICAL

Given SC

Also known as: G-CSF, Nivestim, r-metHuG-CSF, Neupogen

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

Lentivirus Vector rHIV7-shI-TAR-CCR5RZ-transduced Hematopoietic Stem/Progenitor Cells BIOLOGICAL

Given IV

Also known as: lentivirus-transduced hematopoietic progenitor cells

Treatment (R-EPOCH, rHIV7-shI-TAR-CCR5RZ-transduced HSPC)

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 seropositive at or before the time of lymphoma diagnosis; all HIV positive patients are eligible regardless of HIV viral load or antiviral therapy (ART) status; all patients on study will receive ART as per standard guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2
• Biopsy proven lymphoma for which rituximab, etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride (R-EPOCH) is appropriate frontline therapy, e.g., Burkitt lymphoma or diffuse large B-cell lymphoma (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 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 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
• Patients with evidence of hepatitis C virus (HCV) or hepatitis B virus (HBV) infection must have no clinical evidence of cirrhosis
• Serum creatinine \< 2 x the institutional ULN; however, if serum creatinine \> 1.5 x 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 cluster of differentiation (CD)4 cells are greater than 200/mm\^3
• 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 12 months following stem cell infusion; 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
• ELIGIBILITY CRITERIA FOR HSPC TRANSPLANTATION
• Patients must demonstrate \>= 75% disease reduction on computed tomography (CT) scan (confirmed by PET scan) after the third cycle of R-EPOCH relative to baseline, with no evidence of disease progression after the fifth cycle

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
• 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 not limited to:
• Severe AIDS-related wasting
• Severe intractable diarrhea
• Active inadequately treated opportunistic infection of the central nervous system (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 \>= 2 years, may be eligible
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

NCI Lymphoid Malignancies Branch

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Prednisone; Rituximab; Etoposide; Doxorubicin; Vincristine; Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor

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)

Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Glucosides; Glycosides; Carbohydrates; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Amrita Krishnan, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

• Mark J. Roschewski, MD

  NCI Lymphoid Malignancy Branch

  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: December 23, 2014
• First Posted: January 14, 2015
• Study Start: November 20, 2015
• Primary Completion (Estimated): September 8, 2026
• Study Completion (Estimated): September 8, 2026
• Last Updated: November 10, 2025

Record last verified: 2025-11

Locations

US (1)