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AzTrials

AIDS-Related Hodgkin LymphomaPhase 1NCT02378922

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

A Phase 1 study testing Gene-Modified HIV-Protected Hematopoietic Stem Cells, Laboratory Biomarker Analysis and Transplant Conditioning in people with AIDS-Related Hodgkin Lymphoma and AIDS-Related Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 66 years
What is being tested?
Gene-Modified HIV-Protected Hematopoietic Stem Cells, Laboratory Biomarker Analysis and Transplant Conditioning
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
22 Jun 2016to 15 Jun 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 66 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Gene-Modified HIV-Protected Hematopoietic Stem Cells, Laboratory Biomarker Analysis, Transplant Conditioning
Medical subject headings
HIV Infections, Hodgkin Disease, Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Gene-Modified HIV-Protected Hematopoietic Stem CellsBiological

    Receive LVsh5/C46 (Cal-1) transduced CD34+ HSPC IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Transplant ConditioningOther

    Also called conditioning regimen

    Undergo high-dose chemotherapy or chemoradiotherapy

Study groups in NCT02378922
Study groupRoleWhat they receive
Treatment (gene-modified stem cells)ExperimentalCONDITIONING: 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.
Receives: Biological: Gene-Modified HIV-Protected Hematopoietic Stem Cells; Other: Laboratory Biomarker Analysis; Other: Transplant Conditioning

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 15 years

  2. Feasibility of genetic modification, defined as evidence for gene modified CD34+ cells in the infusion product

    Measured: Up to 15 years

  3. 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)

    Measured: Up to 15 years

  4. 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

    Measured: Up to 15 years

  5. Incidence of >= grade 3 toxicity related to the infusion of gene-modified cells, defined by Common Terminology Criteria for Adverse Events version 4.0

    Measured: Up to 15 years

  6. Incidence of confirmed insertional mutagenesis

    Measured: Up to 15 years

  7. Incidence of development of confirmed replication competent lentivirus

    Measured: Up to 15 years

  8. Integration sites of vector sequences in peripheral blood mononuclear cells

    Characterized if clinical symptoms suggest clonal expansion of the HSPC or if molecular assays result in clonal expansion in > 20% of gene-marked cells.

    Measured: Up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Mar 2015 (estimated)
  2. Study start22 Jun 2016
  3. Primary completion15 Jun 2019 (estimated)
  4. Study completion15 Jun 2019 (estimated)

Why it stopped: Administratively closed prior to subject enrollment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02378922
Sponsor's protocol ID
9183
Other IDs
NCI-2015-00149, 9183, P30CA015704
Status last verified
Dec 2018
First submitted
27 Feb 2015
Last updated
27 Dec 2018
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Gene-Modified HIV-Protected Hematopoietic Stem Cells, Laboratory Biomarker Analysis and Transplant Conditioning in people with AIDS-Related Hodgkin Lymphoma and AIDS-Related Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 27 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02378922.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2018.

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