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

Phase 1

Withdrawn

• Conditions: 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
• Interventions: Biological: C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs; Drug: Carmustine; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Drug: O6-Benzylguanine; Drug: Plerixafor

• Registration Number: NCT02343666
• Lead Sponsor: 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 cell...

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety and feasibility of infusing C46/CCR5/P140K lentiviral vector-transduced autologous hematopoietic stem progenitor cells (HSPC) (gene modified, HIV-protected HSPC) after standard first line treatment of lymphoma in patients with HIV infection.
...

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2014-12-30
• Study First Submitted QC: 2015-01-16
• Study First Posted: 2015-01-22
• Study Start: 2016-08-15
• Status Verified: 2018-11
• Last Update Submitted: 2018-11-16
• Last Update Posted: 2018-11-20
• Primary Completion: 2020-08-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Read More

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

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (gene modified HPSC)	C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs	See Detailed Description.
Treatment (gene modified HPSC)	Filgrastim	See Detailed Description.
Treatment (gene modified HPSC)	Laboratory Biomarker Analysis	See Detailed Description.
Treatment (gene modified HPSC)	O6-Benzylguanine	See Detailed Description.
Treatment (gene modified HPSC)	Carmustine	See Detailed Description.
Treatment (gene modified HPSC)	Plerixafor	See Detailed Description.

Primary Outcome Measures

Name	Time	Method
Feasibility of collection: defined as collection of >= 4.0 x 10^6 CD34+ cells/kg for genetic modification	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	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	Up to 180 days after infusion of the gene modified hematopoietic stem progenitor cells
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	Up to 18 months following infusion of CD34+ gene modified hematopoietic stem progenitor cells
Presence of confirmed replication competent lentivirus	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	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 version 4 toxicity >= grade 3 related to the infusion of gene modified cells	Up to 30 days after infusion of CD34+ modified hematopoietic stem progenitor cells
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	Up to 15 years

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States