SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02343666

Developed by Shray Alag, 2019.
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: Lymphoma HIV Infections Acquired Immunodeficiency Syndrome Lymphoma, Non-Hodgkin Hodgkin Disease Immunologic Deficiency Syndromes
HPO: Hodgkin lymphoma Immunodeficiency Lymphoma Non-Hodgkin lymphoma

6 Interventions

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

Description: Given IV

Type: Biological

Treatment (gene modified HPSC)

Name: Carmustine

Description: Given IV

Type: Drug

Treatment (gene modified HPSC)

Name: Filgrastim

Description: Given SC

Type: Biological

Treatment (gene modified HPSC)

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Treatment (gene modified HPSC)

Name: O6-Benzylguanine

Description: Given IV

Type: Drug

Treatment (gene modified HPSC)

Name: Plerixafor

Description: Given SC

Type: Drug

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

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 Lymphoma HIV Infections Acquired Immunodeficiency Syndrome Lymphoma, Non-Hodgkin Hodgkin Disease Immunologic Deficiency Syndromes 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:
Hodgkin lymphoma
Genes 12
POLE FAS FASLG AAGAB ATM DKC1 CASP10 PRKCD RASGRP1 TCF4 COL14A1 RNF43
Immunodeficiency
Genes 196
CYBB MYC MYD88 IL12B IRF2BP2 IL12RB1 RNF168 ACD ATRX AICDA TNFSF12 RTEL1 ACP5 CFTR NCF1 ACTB GATA1 CPLX1 GATA2 BLNK CDH23 FGFRL1 IKZF1 NCF2 CHD1 IRF7 SLC46A1 MAGT1 RREB1 PTEN ADA BCR ADA2 LYST ZBTB24 MEIS2 STAT1 PGM3 HIRA TNFRSF4 TYK2 STIM1 STK4 JAK3 MALT1 STX1A ICOS ANTXR2 PTPRC MBTPS2 TINF2 FCGR3A COG6 PIK3CA CARD9 CCDC47 NFE2L2 PIK3CD PIK3R1 AGL NFKB1 BTK NFKB2 UFD1 IL21 BUB1B PKP1 DKC1 AK2 UNG AKT1 NOP10 BCL10 UROS AP3D1 RAB27A SEC23B TBX1 SDHB SDHC RAC2 SDHD TBCE GP1BB DNMT3B CUL4B DOCK2 FOXN1 RAG1 RAG2 FRAS1 TCF3 CLCA4 LAMTOR2 WAS COMT WIPF1 USB1 CTC1 WHCR NSD2 FOS POLE SMARCAL1 AGPAT2 IRF8 IKBKG XIAP CHD7 SIN3A LMNB2 CAV1 SIK3 LCK PPARG XRCC4 WRAP53 FCN3 NHP2 SKIV2L CR2 TERC SP110 TERT JMJD1C SHANK3 LETM1 CRKL RBCK1 EPG5 TFRC TGFB1 TTC7A IFNGR1 IFNGR2 UNC119 RMRP USP8 ORAI1 LIG4 CORO1A CD3D CD3E KLLN CD3G CD247 BCL11B SEC24C LAT CD19 MS4A1 ISG15 ARVCF DCLRE1C CDCA7 MTHFD1 CD28 IGHM IL21R CD40 CD40LG IRAK4 TNFRSF13C LRRC8A TNFRSF13B PRKCD CD79A CD79B CD81 CTBP1 CARD11 PARN CAVIN1 BSCL2 CTLA4 IGLL1 PRKDC ATM MAPK1 LRBA DCTN4 TNFRSF1B CTPS1 IKBKB NHEJ1 HBB SH2D1A CDC42 IL2RA SPATA5 IL2RG MMUT IL7R HELLS CYBA PRPS1
Lymphoma
Genes 94
BLM MYC CDKN2A KRAS MYD88 RMRP RAG1 RAG2 MALT1 MSH6 RASGRP1 LIG4 TCF4 PMS2 ICOS NRAS WAS WIPF1 CD19 MS4A1 USB1 IGH TINF2 RB1 DCLRE1C TNFSF12 RTEL1 CTC1 CD27 CD28 PIK3R1 PRF1 NTHL1 TP63 POLE HLA-DRB1 NFKB1 NFKB2 RECQL4 RAD54B CHEK2 TNFRSF13C APC MLH1 TNFRSF13B DKC1 BIRC3 XIAP CASP10 NBN PRKCD COL14A1 FOXP1 CD81 PARN NOP10 CCND1 BCL10 BCL2 MSH2 CHD7 CTLA4 ATM BCL6 MAGT1 RUNX1 TNFRSF1B XRCC4 WRAP53 PTEN MDM2 FAS NHP2 ADA FASLG CR2 SH2D1A TERC AAGAB KIT TERT NSUN2 IL2RG LYST RNF43 ZAP70 DNASE1L3 TP53 RAD54L ITK STAT3 IL7R KIF11 PNP
Non-Hodgkin lymphoma
Genes 22
MYC FAS ADA FASLG IGH KIT BIRC3 CASP10 NBN CD28 MALT1 PRKCD RASGRP1 FOXP1 PIK3R1 NTHL1 POLE CCND1 BCL10 CTLA4 ATM TNFRSF1B