HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

NCT02343666 | Withdrawn Phase 1 DMC FDA Drug

• 5 other identifiers: 2673.00NCI-2014-023952673P30CA015704R01HL116217
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot phase I trial studies the side effects and best dose of human immunodeficiency virus (HIV)-resistant gene modified stem cells in treating HIV-positive patients who are undergoing first-line treatment for Hodgkin or Non-Hodgkin Lymphoma. Stem cells are collected from the patient and HIV-resistance genes are placed into the stem cells. The stem cells are then re-infused into the patient. These genetically modified stem cells may help the body make cells that are resistant to HIV infection.

Conditions

Human Immunodeficiency Virus 1 Positive; Stage I Adult Hodgkin Lymphoma; Stage I Adult Non-Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult Non-Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Non-Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (8)

• Feasibility of collection: defined as collection of >= 4.0 x 10^6 CD34+ cells/kg for genetic modification

  Up to 28 days after completion of last course of first line treatment for lymphoma

• Feasibility of infusion of gene modified cells: defined as engraftment of >= 1% gene modified cells

  Engraftment of \>= 1% gene modified cells.

  Up to 28 days after infusion of gene-modified cells to 15 years post-transfusion

• Feasibility of O6-benzylguanine/carmustine in vivo selection: defined as selection of gene modified cells to a level >= 10% of peripheral blood cells

  Up to 180 days after infusion of the gene modified hematopoietic stem progenitor cells

• Feasibility of structured treatment interruption: defined as the ability to achieve >= 10% gene modified cell engraftment level and maintain CD4 counts and plasma viremia at levels required for structured treatment interruption eligibility

  Up to 18 months following infusion of CD34+ gene modified hematopoietic stem progenitor cells

• Presence of confirmed replication competent lentivirus

  Any development of confirmed replication competent lentivirus in any patient receiving gene modified cells during the study will be recorded.

  Up to 15 years

• Presence of insertional mutagenesis

  Confirmed insertional mutagenesis in any patient who received gene modified cells during the study

  Up to 15 years

• Safety of infusion of gene modified cells: defined as Common Terminology Criteria for Adverse Events version 4 toxicity >= grade 3 related to the infusion of gene modified cells

  Up to 30 days after infusion of CD34+ modified hematopoietic stem progenitor cells

• Safety of O6-benzylguanine/carmustine in vivo selection, defined as < 25% of patients developing Common Terminology Criteria for Adverse Events version 4 toxicity >= grade 3 associated with O6-benzylguanine/carmustine administration

  Up to 15 years

Study Arms (1)

Treatment (gene modified HPSC)

EXPERIMENTAL

See Detailed Description.

Biological: C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs; Drug: Carmustine; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Drug: O6-Benzylguanine; Drug: Plerixafor

Interventions

C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs BIOLOGICAL

Given IV

Treatment (gene modified HPSC)

Carmustine DRUG

Given IV

Also known as: BCNU, Becenum, Becenun, BiCNU, Bis(chloroethyl) Nitrosourea, Bis-Chloronitrosourea, Carmubris, Carmustin, Carmustinum, FDA 0345, Gliadel, N,N'-Bis(2-chloroethyl)-N-nitrosourea, Nitrourean, Nitrumon, SK 27702, SRI 1720, WR-139021

Treatment (gene modified HPSC)

Filgrastim BIOLOGICAL

Given SC

Also known as: Filgrastim XM02, Filgrastim-sndz, G-CSF, Granix, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim, Zarxio

Treatment (gene modified HPSC)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (gene modified HPSC)

O6-Benzylguanine DRUG

Given IV

Also known as: 6-O-BENZYLGUANINE, O(6)-Benzylguanine

Treatment (gene modified HPSC)

Plerixafor DRUG

Given SC

Also known as: AMD 3100, JM-3100, Mozobil, SDZ SID 791

Treatment (gene modified HPSC)

Eligibility Criteria

• Age: 18 Years - 66 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 seropositive
• Stable, continuous antiretroviral treatment, defined as a multi-drug regimen (excluding zidovudine, also known as azidothymidine \[AZT\], Retrovir) prior to enrollment, as demonstrated by HIV plasma viral load \< 50 copies/mL
• Previously untreated non-Hodgkin lymphoma or Hodgkin lymphoma; all stages of disease are allowed; also eligible are patients who have started or completed one or more cycles of treatment as part of a planned first line regimen, or those who have received local radiation or surgery or corticosteroids for disease control
• Planned treatment with standard first line therapy for non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL)
• Karnofsky performance score \>= 70%
• Subjects must agree to use effective means to prevent conception from enrollment through completion of the study
• Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of enrollment
• Subjects must be on a prophylactic regimen for Pneumocystis jiroveci pneumonia, or agree to begin such treatment, if CD4+ cell counts are observed to be =\< 200/ul in peripheral blood
• Able to understand, and the willingness to give, informed consent for the study

You may not qualify if:

• Central nervous system (CNS) lymphoma: CNS involvement by lymphoma, including parenchymal brain or spinal cord lymphoma or known presence of leptomeningeal disease prior to registration
• Patients with renal, hepatic, pulmonary, or cardiac disease that exclude delivery of standard chemotherapy
• Active (uncontrolled) infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV)
• Hepatitis B surface antigen positive
• Hepatitis C virus (HCV) antibody positive and detectable HCV quantitative ribonucleic acid (RNA), with clinical evidence of cirrhosis as determined by the principal investigator
• Requiring active treatment for Toxoplasma gondii infection
• Malignancy other than lymphoma, unless (1) in complete remission and more than 5 years from last treatment, or (2) cervical/anal squamous cell carcinoma in situ or (3) superficial basal cell and squamous cell cancers of the skin
• 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 concurrent or past medical condition that, in the opinion of the investigator, would exclude the subject from participation
• Patients who have received a vaccine for HIV-1 or any prior gene modified cell product, at any time
• A medical history of noncompliance with HAART or medical therapy
• Pregnant women or nursing mothers
• Use of zidovudine as part of the HAART regimen (a drug substitution for zidovudine at the time of study entry is allowed)
• Known hypersensitivity to any of the products used in the trial - G-CSF (Neupogen, filgrastim), plerixafor (Mozobil), or any components of the chemotherapeutic agents or O6BG/BCNU in vivo selection regimens

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Carmustine; carmustine, poliferprosan 20 drug combination; Filgrastim; Granulocyte Colony-Stimulating Factor; O(6)-benzylguanine; plerixafor; ferric pyrophosphate

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Mazyar Shadman

  Fred Hutch/University of Washington Cancer Consortium

  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 30, 2014
• First Posted: January 22, 2015
• Study Start: August 15, 2016
• Primary Completion: August 1, 2020
• Last Updated: November 20, 2018

Record last verified: 2018-11

Locations

US (1)