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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2017 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT02343666
First received: December 30, 2014
Last updated: January 19, 2017
Last verified: January 2017
  Purpose
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 Intervention Phase
HIV Infection
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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
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

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • 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 ]
  • 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.

  • 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 HSPC ]
  • Feasibility of STI: defined as the ability to achieve >= 10% gene modified cell engraftment level and maintain CD4 counts and plasma viremia at levels required for STI eligibility [ Time Frame: Up to 18 months following infusion of CD34+ gene modified HSPC ]
  • 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.

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

  • Safety of infusion of gene modified cells: defined as Common Terminology Criteria for Adverse Events (CTCAE) version (v.)4 toxicity >= grade 3 related to the infusion of gene modified cells [ Time Frame: Up to 30 days after infusion of CD34+ modified HSPC ]
  • Safety of O6-benzylguanine/carmustine in vivo selection, defined as < 25% of patients developing CTCAE v.4 toxicity >= grade 3 associated with O6-benzylguanine/carmustine administration [ Time Frame: Up to 15 years ]

Estimated Enrollment: 13
Actual Study Start Date: August 15, 2016
Estimated Primary Completion Date: August 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
  • 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:
  • 6-O-BENZYLGUANINE
  • O(6)-Benzylguanine
Drug: Plerixafor
Given SC
Other Names:
  • AMD 3100
  • JM-3100
  • Mozobil
  • SDZ SID 791

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  • HIV-1 seropositive
  • Stable, continuous antiretroviral treatment for at least three months prior to enrollment, defined as a multi-drug regimen (excluding zidovudine, also known as azidothymidine [AZT], Retrovir)
  • 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02343666

Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ann E. Woolfrey    206-667-4453    awoolfre@fredhutch.org   
Principal Investigator: Ann E. Woolfrey         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Ann Woolfrey Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT02343666     History of Changes
Other Study ID Numbers: 2673.00
NCI-2014-02395 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2673
2673.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( US NIH Grant/Contract Award Number )
R01HL116217 ( US NIH Grant/Contract Award Number )
Study First Received: December 30, 2014
Last Updated: January 19, 2017

Additional relevant MeSH terms:
Infection
Communicable Diseases
Lymphoma
HIV Infections
Acquired Immunodeficiency Syndrome
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Slow Virus Diseases
Lenograstim
Carmustine
O(6)-benzylguanine
JM 3100
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on March 30, 2017