SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT02343666

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

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

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.

NCT02343666 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
MeSH:HIV Infections Acquired Immunodeficiency Syndrome Lymphoma Lymphoma, Non-Hodgkin Hodgkin Disease
HPO:Hodgkin lymphoma Lymphoma Non-Hodgkin lymphoma

6 Interventions

Name: C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs

Description: Given IV
Type: Biological
Group Labels: 1

Treatment (gene modified HPSC)

Name: Carmustine

Description: Given IV
Type: Drug
Group Labels: 1

Treatment (gene modified HPSC)

Name: Filgrastim

Description: Given SC
Type: Biological
Group Labels: 1

Treatment (gene modified HPSC)

Name: Laboratory Biomarker Analysis

Description: Correlative studies
Type: Other
Group Labels: 1

Treatment (gene modified HPSC)

Name: O6-Benzylguanine

Description: Given IV
Type: Drug
Group Labels: 1

Treatment (gene modified HPSC)

Name: Plerixafor

Description: Given SC
Type: Drug
Group Labels: 1

Treatment (gene modified HPSC)


Primary Outcomes

Measure: Feasibility of collection: defined as collection of >= 4.0 x 10^6 CD34+ cells/kg for genetic modification

Time: Up to 28 days after completion of last course of first line treatment for lymphoma

Description: Engraftment of >= 1% gene modified cells.

Measure: Feasibility of infusion of gene modified cells: defined as engraftment of >= 1% gene modified cells

Time: Up to 28 days after infusion of gene-modified cells to 15 years post-transfusion

Measure: Feasibility of O6-benzylguanine/carmustine in vivo selection: defined as selection of gene modified cells to a level >= 10% of peripheral blood cells

Time: Up to 180 days after infusion of the gene modified hematopoietic stem progenitor cells

Measure: 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

Time: Up to 18 months following infusion of CD34+ gene modified hematopoietic stem progenitor cells

Description: Any development of confirmed replication competent lentivirus in any patient receiving gene modified cells during the study will be recorded.

Measure: Presence of confirmed replication competent lentivirus

Time: Up to 15 years

Description: Confirmed insertional mutagenesis in any patient who received gene modified cells during the study

Measure: Presence of insertional mutagenesis

Time: Up to 15 years

Measure: 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

Time: Up to 30 days after infusion of CD34+ modified hematopoietic stem progenitor cells

Measure: 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

Time: Up to 15 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 P140K

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 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 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 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 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 HIV Infections Acquired Immunodeficiency Syndrome Lymphoma Lymphoma, Non-Hodgkin Hodgkin Disease 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. --- P140K ---

Determine the correlation between the level of MGMT(P140K) marking with toxicity and response to O6BG/BCNU chemotherapy. --- P140K ---

STEM CELL INFUSION: Patients receive CD34+ gene-modified C46/CCR5/P140K lentiviral vector-transduced autologous HSPC intravenously (IV) within 2 to 8 days, but no later than 28 days, after completion of the last cycle of first line treatment for lymphoma. --- P140K ---



HPO Nodes


HPO: