SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT00001566

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Pilot Study of Autologous T-Cell Transplantation With Vaccine Driven Expansion of Anti-Tumor Effectors After Cytoreductive Therapy in Metastatic Pediatric Sarcomas

This is a single arm study. The tumor specimen is analyzed for the presence of a fusion protein which corresponds to available peptides. Patients undergo T cell harvest 10 days after an initial priming peptide-pulsed antigen presenting cell (APC) vaccine is performed. Fresh APCs are utilized for initial priming vaccination. All subsequent vaccinations will use cryopreserved APCs. Minimum number of APCs administered per vaccination is 100,000/kg and maximum is 100,000,000/kg. Patients undergo cytoreductive therapy for the treatment of their particular malignancy. This therapy usually consists of multiagent chemotherapy in the context of a separate protocol. Following chemotherapy, infusion of harvested T cells followed by infusion of peptide-pulsed APC vaccinations occurs every 6 weeks for a total of 3 post-priming vaccinations. Influenza vaccine is administered by intramuscular injection concurrent to peptide-pulsed APC vaccines. Interleukin -2 (IL-2) is administered as a continuous intravenous (IV) infusion for 4 days/week for 3 successive weeks starting on the same day as T cell /peptide-pulsed infusions.

NCT00001566 Ewing's Sarcoma Rhabdomyosarcoma
MeSH: Sarcoma Rhabdomyosarcoma Sarcoma, Ewing
HPO: Ewing sarcoma Rhabdomyosarcoma Sarcoma Soft tissue sarcoma

3 Interventions

Name: therapeutic autologous dendritic cells

Description: 3 syringes containing 1 x 10^6peptide pulsed dendritic cells

Type: Biological

Peptide vaccine/autologous T cell transplant/indinavir therapy

Name: indinavir sulfate

Description: Oral dose, 350 mg/m^2 administered every 8 hours. Maximum dose is 800 mg every 8 hours.

Type: Drug

Peptide vaccine/autologous T cell transplant/indinavir therapy

Name: peripheral blood stem cell transplantation

Description: Harvested autologous T cells, minimum dose 1 x 10^6/kg will be thawed rapidly in 37 degree water bath and infused sequentially over 5-15 minutes.

Type: Procedure

Peptide vaccine/autologous T cell transplant/indinavir therapy


Primary Outcomes

Description: Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0. Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. Non-tumor specific peptide:HPV16E7 MLDLQPETT-MET-9-THR. See protocol link module for additional information re: peptides.

Measure: Number of Participants With an Immune Response to Tumor-specific and Non-tumor Specific Peptides During a Period of Immune Reconstitution

Time: 20 weeks post vaccination

Description: CD4 counts were measured from peripheral blood using standard flow cytometric techniques at the following timepoints: 2 months post-chemotherapy, 4 months post-chemotherapy and 6 months post-chemotherapy. To be eligible for evaluation for this endpoint, patient much have been <10 years of age and sustained a CD4 count of <300 cells/mcl upon completion of standard therapy. Recovery was defined as a CD4 count > 500 cells/mcl at any timepoint within 6 months of completing chemotherapy.

Measure: The Percent of Patients Who Recover CD4 Counts Within 6 Months of Completion of Chemotherapy

Time: 2 to 6 months

Description: Immune responses were measured following 3 sequential influenza vaccines during the same period as the peptide-pulsed dendritic cell vaccines.

Measure: Number of Participants With an Immune Response to the Translocation Breakpoint Peptide

Time: 5 years

Description: Immune response was defined as a percent specific lysis of >10% following challenge with peptide pulsed targets, or interferon gamma production following challenge with peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0.

Measure: Number of Participants With an Immune Response to Non-Tumor-specific Peptide E7

Time: 5 years

Description: Immune response was defined as a percent specific lysis of >10% following challenge with tumor peptide pulsed targets, or interferon gamma production following challenge with tumor peptide pulsed targets >2-fold that found with no-peptide controls or a proliferation index >3.0 to tumor peptide targets.Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. See protocol link module for additional information re: peptides.

Measure: Number of Participants With an Immune Response to Tumor-Specific Peptides at the Time of Presentation

Time: Once per enrollment

Secondary Outcomes

Description: Overall survival is defined as the time between the first day of treatment to the day of death.

Measure: Percentage of Participants Overall Survival

Time: 5 years

Description: Event free survival is calculated from the date of diagnosis for patients enrolled with newly diagnosed metastatic disease and from the date of the last recurrence detection before enrollment on this study for patients with recurrent disease.

Measure: Percent of Participants: Event Free Survival

Time: 5 years

Description: Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Measure: Number of Participants With Adverse Events

Time: 5 years

Description: Overall survival is defined as the time between the first day of treatment to the day of death.

Measure: Median Overall Survival

Time: 5.4 years

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 M9T

Tumor specific peptides: Ewings sarcoma Type 1: EF-1 (EWS/FLI-1)*SSSYGQQN/PSYDSVRRGA,Ewing's Sarcoma Type 2: EF-2 (EWS/FLI-2)* SSSYGQ/QSSLLAYNT, Alveolar rhabdomyosarcoma: PXFK (PAX3/FKHR)† TIGNGLSPQ/NSIRHNLSL. Non-tumor specific peptide:HPV16E7 MLDLQPETT-MET-9-THR. See protocol link module for additional information re: peptides.. --- MET-9-THR ---



HPO Nodes


HPO:
Ewing sarcoma
Genes 4
EWSR1 BRD4 NUTM1 RB1
Rhabdomyosarcoma
Genes 21
BUB3 HRAS FOXO1 MLH1 CEP57 TRIP13 SLC22A18 NBN MSH6 DICER1 PMS2 MSH2 PAX3 KEAP1 PAX7 BUB1 NF1 BUB1B MC1R NRAS PTCH1
Sarcoma
Genes 116
VEGFC CDKN1A CDKN1B FOXO1 CDKN2A KRAS CDKN2B CDKN2C GDF5 FLNA ATP6V1B2 PMS2 FLT4 NRAS KRT17 PDGFB PDGFRA RB1 PDGFRB SRC MC1R WRN WT1 APC CASP10 NBN GJC2 NR4A3 RPS19 TSC1 TSC2 EWSR1 EXT1 EXT2 MSH2 KEAP1 IDH1 IDH2 REST DCC PTCH1 PTEN MDM2 FAS FASLG SSX1 SSX2 TRIP13 DICER1 PTH1R AXIN2 MEN1 NUTM1 TBX18 SLC22A18 MSH6 RASGRP1 FAM20C BMPR1A BMPR1B KLLN PTPN11 DLC1 MTAP NF1 ANTXR2 LMNA BRAF NF2 ABCA5 PIK3CA KCNH1 ELMO2 SQSTM1 BRD4 DHCR24 RECQL4 BUB1 BUB1B CHEK2 HRAS PTCH2 MLH1 PRKAR1A FLCN PRKCD SPRED1 AKT1 ASPSCR1 TAF15 FGFR3 PAX3 PLCD1 CDC73 GREM1 PAX7 GNAS CTNNB1 FH BUB3 SUFU MAP2K1 CEP57 KIT EP300 PRLR SEC23B SDHA TP53 NOTCH3 SDHB SDHC SDHD COL1A1 SOS1 FOXC2
Soft tissue sarcoma
Genes 91
VEGFC CDKN1A CDKN1B FOXO1 KRAS CDKN2B CDKN2C SLC22A18 FLNA MSH6 RASGRP1 ATP6V1B2 FAM20C BMPR1A PMS2 FLT4 KLLN PTPN11 DLC1 MTAP NF1 ANTXR2 NRAS KRT17 BRAF NF2 PDGFB PDGFRA ABCA5 PDGFRB PIK3CA KCNH1 ELMO2 DHCR24 SRC BUB1 BUB1B MC1R HRAS PTCH2 APC MLH1 PRKAR1A FLCN CASP10 NBN PRKCD SPRED1 GJC2 AKT1 TSC1 TSC2 ASPSCR1 MSH2 FGFR3 PAX3 PLCD1 CDC73 KEAP1 GREM1 PAX7 REST CTNNB1 DCC FH PTCH1 BUB3 PTEN FAS FASLG SUFU MAP2K1 SSX1 SSX2 CEP57 TRIP13 KIT DICER1 EP300 PRLR SEC23B TP53 NOTCH3 SDHB SDHC SDHD AXIN2 COL1A1 MEN1 SOS1 FOXC2