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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02343666
Recruitment Status : Withdrawn (Administrative closure prior to any enrollments)
First Posted : January 22, 2015
Last Update Posted : November 20, 2018
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Biological: C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs Drug: Carmustine Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: O6-Benzylguanine Drug: Plerixafor Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Trial of Gene-Modified Stem Cells to Generate HIV-Resistant Cells in Conjunction With Standard Chemotherapy for Treatment of Lymphoma in Patients With HIV Infection
Actual Study Start Date : August 15, 2016
Estimated Primary Completion Date : August 1, 2020

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Treatment (gene modified HPSC)
See Detailed Description.
Biological: C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs
Given IV

Drug: Carmustine
Given IV
Other Names:
  • 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

Biological: Filgrastim
Given SC
Other Names:
  • Filgrastim XM02
  • Filgrastim-sndz
  • G-CSF
  • Granix
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tbo-filgrastim
  • Tevagrastim
  • Zarxio

Other: Laboratory Biomarker Analysis
Correlative studies

Drug: O6-Benzylguanine
Given IV
Other Names:
  • O(6)-Benzylguanine

Drug: Plerixafor
Given SC
Other Names:
  • AMD 3100
  • JM-3100
  • Mozobil
  • SDZ SID 791

Primary Outcome Measures :
  1. Feasibility of collection: defined as collection of >= 4.0 x 10^6 CD34+ cells/kg for genetic modification [ Time Frame: Up to 28 days after completion of last course of first line treatment for lymphoma ]
  2. Feasibility of infusion of gene modified cells: defined as engraftment of >= 1% gene modified cells [ Time Frame: Up to 28 days after infusion of gene-modified cells to 15 years post-transfusion ]
    Engraftment of >= 1% gene modified cells.

  3. Feasibility of O6-benzylguanine/carmustine in vivo selection: defined as selection of gene modified cells to a level >= 10% of peripheral blood cells [ Time Frame: Up to 180 days after infusion of the gene modified hematopoietic stem progenitor cells ]
  4. 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 [ Time Frame: Up to 18 months following infusion of CD34+ gene modified hematopoietic stem progenitor cells ]
  5. Presence of confirmed replication competent lentivirus [ Time Frame: Up to 15 years ]
    Any development of confirmed replication competent lentivirus in any patient receiving gene modified cells during the study will be recorded.

  6. Presence of insertional mutagenesis [ Time Frame: Up to 15 years ]
    Confirmed insertional mutagenesis in any patient who received gene modified cells during the study

  7. 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 [ Time Frame: Up to 30 days after infusion of CD34+ modified hematopoietic stem progenitor cells ]
  8. 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 [ Time Frame: Up to 15 years ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 66 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02343666

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United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Center
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
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Principal Investigator: Mazyar Shadman Fred Hutch/University of Washington Cancer Consortium
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Responsible Party: Fred Hutchinson Cancer Center Identifier: NCT02343666    
Other Study ID Numbers: 2673.00
NCI-2014-02395 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2673.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
R01HL116217 ( U.S. NIH Grant/Contract )
First Posted: January 22, 2015    Key Record Dates
Last Update Posted: November 20, 2018
Last Verified: November 2018

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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HIV Infections
Acquired Immunodeficiency Syndrome
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Genital Diseases
Urogenital Diseases
Immunologic Deficiency Syndromes
Slow Virus Diseases
Adjuvants, Immunologic
Immunologic Factors