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

NCT02378922 | Withdrawn Phase 1 DMC

• 3 other identifiers: 9183NCI-2015-00149P30CA015704
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

AIDS-Related Hodgkin Lymphoma; AIDS-Related Non-Hodgkin Lymphoma; HIV Infection; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (8)

• 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

  Up to 15 years

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

  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)

  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

  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

  Up to 15 years

• Incidence of confirmed insertional mutagenesis

  Up to 15 years

• Incidence of development of confirmed replication competent lentivirus

  Up to 15 years

• 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.

  Up to 15 years

Study Arms (1)

Treatment (gene-modified stem cells)

EXPERIMENTAL

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; Other: Laboratory Biomarker Analysis; Other: Transplant Conditioning

Interventions

Gene-Modified HIV-Protected Hematopoietic Stem Cells BIOLOGICAL

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

Treatment (gene-modified stem cells)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (gene-modified stem cells)

Transplant Conditioning OTHER

Undergo high-dose chemotherapy or chemoradiotherapy

Also known as: conditioning regimen

Treatment (gene-modified stem cells)

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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

HIV Infections; Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

Transplantation Conditioning

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Immunosuppression Therapy; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Hans-Peter Kiem

  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: February 27, 2015
• First Posted: March 4, 2015
• Study Start: June 22, 2016
• Primary Completion: June 15, 2019
• Study Completion: June 15, 2019
• Last Updated: December 27, 2018

Record last verified: 2018-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)