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Gene-Modified HIV-Protected Stem Cell Transplant in Treating Patients With HIV-Associated Lymphoma

This study has suspended participant recruitment.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02378922
First Posted: March 4, 2015
Last Update Posted: January 10, 2017
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
  Purpose
This clinical trial studies gene-modified, human immunodeficiency virus (HIV)-protected stem cell transplant in treating patients with HIV-associated lymphoma. Stem cells, or cells which help form blood, are collected from the patient and stored. They are treated in the laboratory to help protect the immune system from HIV. Chemotherapy is given before transplant to kill lymphoma cells and to make room for new stem cells to grow. Patients then receive the stem cells that were collected from them before chemotherapy and have been genetically modified to replace the stem cells killed by the chemotherapy.

Condition Intervention Phase
AIDS-Related Hodgkin Lymphoma AIDS-Related Non-Hodgkin Lymphoma HIV Infection Recurrent Hodgkin Lymphoma Recurrent Non-Hodgkin Lymphoma Biological: Gene-Modified HIV-Protected Hematopoietic Stem Cells Other: Laboratory Biomarker Analysis Other: Transplant Conditioning Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous Transplantation and Stem Cell-Based Gene Therapy With LVsh5/C46 (CAL-1), a Dual Anti-HIV Lentiviral Vector, for the Treatment of HIV-Associated Lymphoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Feasibility of collection of >= 2.1 x 10^6 CD34+ cells/kg for backup cryopreservation and collection of an additional >= 2.5 x 10^6 CD34+ cells/kg for genetic modification [ Time Frame: Up to 15 years ]
  • Feasibility of genetic modification, defined as evidence for gene modified CD34+ cells in the infusion product [ Time Frame: Up to 15 years ]
  • Feasibility of infusion of gene-modified cells, defined as engraftment of >= 1% gene-modified cells at the time of hematopoietic recovery from conditioning (absolute neutrophil count >= 500/mcL, platelets >= 100,000/mcL for three consecutive evaluations) [ Time Frame: Up to 15 years ]
  • Feasibility of stem cell infusion (STI), defined as the ability to achieve engraftment level and maintain CD4 counts and plasma viremia at levels required for STI eligibility [ Time Frame: Up to 15 years ]
  • Incidence of >= grade 3 toxicity related to the infusion of gene-modified cells, defined by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 15 years ]
  • Incidence of confirmed insertional mutagenesis [ Time Frame: Up to 15 years ]
  • Incidence of development of confirmed replication competent lentivirus [ Time Frame: Up to 15 years ]
  • Integration sites of vector sequences in peripheral blood mononuclear cells [ Time Frame: Up to 15 years ]
    Characterized if clinical symptoms suggest clonal expansion of the HSPC or if molecular assays result in clonal expansion in > 20% of gene-marked cells.


Estimated Enrollment: 5
Study Start Date: June 2016
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (gene-modified stem cells)

CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.

STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant on day 0.

Note: Patients continue to receive HAART throughout treatment, with a 7-day break for apheresis. Patients may be eligible for a structured treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant with gene-modified cells.

Biological: Gene-Modified HIV-Protected Hematopoietic Stem Cells
Receive LVsh5/C46 (Cal-1) transduced CD34+ HSPC IV
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Transplant Conditioning
Undergo high-dose chemotherapy or chemoradiotherapy
Other Name: conditioning regimen

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety and feasibility of infusing gene-modified, HIV-protected hematopoietic stem/progenitor cells (HSPC) after high-dose chemotherapy for treatment of acquired immune deficiency syndrome (AIDS)-related lymphoma.

II. To observe the change in gene-modified cell levels before and after antiviral treatment interruption.

SECONDARY OBJECTIVES:

I. To evaluate the molecular and clonal composition of gene-modified cells after hematopoietic cell transplant (HCT).

II. To describe time to disease progression, progression-free survival, treatment-related mortality, time to neutrophil and platelet recovery, and incidence of infections.

TERTIARY OBJECTIVES:

I. To evaluate the effect of procedure on HIV-specific immune reconstitution.

II. To observe the effect of HIV infection on the presence of gene-marked cells as determined by deoxyribonucleic (DNA) polymerase chain reaction (PCR).

OUTLINE:

CONDITIONING: Patients undergo high-dose chemotherapy or chemoradiotherapy according to institutional guidelines.

STEM CELL INFUSION: Patients undergo hematopoietic stem cell transplant with LVsh5/C46 (Cal-1) transduced autologous CD34+ hematopoietic stem/progenitor cells (HSPC) on day 0.

Note: Patients continue to receive highly active antiretroviral therapy (HAART) throughout treatment, with a 7-day break for apheresis. Patients may be eligible for a structured treatment interruption of up to 12 weeks after autologous hematopoietic stem cell transplant with gene-modified cells.

After completion of study treatment, patients are followed up periodically for 2 years, every 6 months for 3 years, and then annually for 15 years post-HCT.

  Eligibility

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.


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 before enrollment, defined as a multi-drug regimen (excluding azidothymidine [AZT])
  • HIV plasma viral load < 50 copies/ml
  • Non-Hodgkin or Hodgkin lymphoma without active central nervous system (CNS) involvement associated with poor prognosis with medical therapy alone or for which autologous peripheral blood stem cell (PBSC) transplant is indicated:

    • Hodgkin's lymphoma beyond first remission or first partial remission or induction failure with subsequent response to salvage therapy
    • Non-Hodgkin's lymphoma beyond first remission or first partial remission or induction failure with subsequent response to salvage therapy
    • Chemotherapy responsive disease
  • Karnofsky performance score >= 70%
  • Subjects must agree to use effective contraception 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 carinii pneumonia, or agree to begin such treatment, if CD4+ cell counts are observed to be =< 200/ul in peripheral blood
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Renal disease: serum creatinine > 2 times upper limit of normal
  • Liver disease: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 times the upper limits of normal, unless determined to be a result of the primary hematologic malignancy
  • Serum bilirubin greater than 3 times the upper limit of normal, unless attributed to Gilbert's syndrome
  • Pulmonary disease: forced vital capacity (FVC) < 60% predicted
  • Pulmonary disease: forced expiratory volume in 1 second (FEV1) < 60% predicted
  • Pulmonary disease: diffusion capacity of the lung for carbon monoxide (DLCO) parameters < 60% predicted (corrected for hemoglobin)
  • Cardiac insufficiency: left ventricular ejection fraction (LVEF) < 50% or coronary artery disease requiring treatment
  • Active 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
  • Requiring active treatment for Toxoplasma gondii
  • Planned radiation therapy after transplant
  • 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)
  • A medical history of noncompliance with HAART or medical therapy
  • Any concurrent or past medical condition that, in the opinion of the Investigator, would exclude the subject from participation or any psychosocial conditions that would hinder study compliance or follow-up, at the discretion of the Investigator
  • Receipt of a vaccine for HIV-1 or any prior gene modified cell product, at any time
  • Known hypersensitivity to any of the products used in the trial-G-CSF (Neupogen), plerixafor, or any planned components of conditioning regimens
  • Pregnant or nursing women
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02378922


Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Hans-Peter Kiem Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT02378922     History of Changes
Other Study ID Numbers: 9183
NCI-2015-00149 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
9183 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: February 27, 2015
First Posted: March 4, 2015
Last Update Posted: January 10, 2017
Last Verified: January 2017

Additional relevant MeSH terms:
Lymphoma
HIV Infections
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, AIDS-Related
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
Lymphoma, B-Cell