SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02923986

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

A Phase Ib/IIa Single-arm, Open-label Clinical Trial to Evaluate the Safety, Pharmacokinetics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination With Dasatinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) Including Chronic Phase Patients Who Have Failed Initial Tyrosine Kinase Inhibitor (TKI) Therapy, Accelerated or Blast Phase, Ph+ Acute Myeloid Leukemia (AML) or High-risk Ph+ Myelodysplastic Syndrome (MDS)

The primary objective of the Phase Ib study is to determine the dose-limiting toxicity (DLT) and maximal tolerated dose (MTD) of BP1001 in combination with dasatinib in patients with with Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML) including chronic phase patients who have failed initial tyrosine kinase inhibitor (TKI) therapy, accelerated or blast phase, Ph+ Acute Myeloid Leukemia (AML) or High-risk Ph+ Myelodysplastic Syndrome (MDS). The primary objective of the Phase IIa study is to assess the efficacy of the combination of BP1001 and dasatinib in patients with Ph+ CML, Ph+AML, or high-risk Ph+ MDS.

NCT02923986 Chronic Myelogenous Leukemia, Ph1-Positive Acute Myeloid Leukemia Myelodysplastic Syndrome
MeSH: Syndrome Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive
HPO: Acute megakaryocytic leukemia Acute myeloid leukemia Chronic myelogenous leukemia Leukemia Myelodysplasia Myeloid leukemia

3 Interventions

Name: BP1001 (varying dose)

Description: BP1001 (varying dose)

Type: Drug

BP1001 (varying dose) + Dasatinib

Name: BP1001 (fixed dose)

Description: BP1001 (fixed dose)

Type: Drug

BP1001 (fixed dose) + Dasatinib

Name: Dasatinib

Description: Dasatinib

Type: Drug

BP1001 (varying dose) + Dasatinib BP1001 (fixed dose) + Dasatinib


Primary Outcomes

Description: Phase 1b portion of the study: Determine the dose limiting toxicity of BP1001 in combination with Das

Measure: Dose Limiting Toxicity of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria

Time: 240 days

Description: Phase 1b portion of the study: Determine the maximum tolerated dose of BP1001 in combination with Das

Measure: Maximum Tolerated Dose of BP1001 using non-hematologic and hematologic parameters per NCI CTCAE criteria

Time: 240 days

Description: Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das

Measure: Efficacy of the combination of BP1001 and Das using hematologic response by bone marrow aspirate or biopsy and complete blood counts

Time: 240 days

Description: Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das

Measure: Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy

Time: 240 days

Description: Phase IIa portion of the study: Assess the efficacy of the combination of BP1001 and Das

Measure: Efficacy of the combination of BP1001 and Das using molecular response (PCR) by bone marrow aspirate or biopsy

Time: 240 days

Secondary Outcomes

Description: Evaluate Safety of BP1001 in combination with Das

Measure: Safety of BP1001 in combination with Das using non-hematologic and hematologic parameters per NCI CTCAE criteria

Time: 30 days

Description: Determine whether the combination of BP1001 and Das provides greater efficacy (Hematologic Response) than Das alone (by historical comparison)

Measure: Efficacy of the combination of BP1001 and Das using hematologic response by bone marrow aspirate or biopsy and complete blood counts versus Das alone by historical outcome comparison

Time: 240 days

Description: Determine whether the combination of BP1001 and Das provides greater efficacy (Cytogenetic Response) than Das alone (by historical comparison)

Measure: Efficacy of the combination of BP1001 and Das using cytogenetic response (karyotyping) by bone marrow aspirate or biopsy versus Das alone by historical outcome comparison

Time: 240 days

Description: Determine whether the combination of BP1001 and Das provides greater efficacy (Molecular Response) than Das alone (by historical comparison)

Measure: Efficacy of the combination of BP1001 and Das using molecular response (PCR) by bone marrow aspirate or biopsy versus Das alone by historical outcome comparison

Time: 240 days

Description: Evaluate in vivo PK of BP1001 when given alone and in combination with Das

Measure: In vivo PK using plasma to compute half life and elimination

Time: 30 days

Description: Assess time to response from administration of BP1001 + Das to hematologic response

Measure: Time to Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts

Time: 30 days

Description: Assess time to response from administration of BP1001 + Das to cytogenetic response

Measure: Time to Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate

Time: 30 days

Description: Assess time to response from administration of BP1001 + Das to molecular response

Measure: Time to Response using molecular response (PCR) using bone marrow biopsy or aspirate

Time: 30 days

Description: Assess duration of response from day of response to day of disease progression

Measure: Duration of Response using hematologic response using bone marrow biopsy or aspirate and complete blood counts from day of response to day of disease progression

Time: 30 days

Description: Assess duration of response from day of response to day of disease progression

Measure: Duration of Response using cytogenetic response (karyotyping) using bone marrow biopsy or aspirate from day of response to day of disease progression

Time: 30 days

Description: Assess duration of response from day of response to day of disease progression

Measure: Duration of Response using molecular response (PCR) using bone marrow biopsy or aspirate from day of response to day of disease progression

Time: 30 days

Description: Assess overall survival from date of study entry to study closure

Measure: Overall Survival from date of study entry to study closure

Time: 240 days

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 T315I

× 0.74 [if female] x 1.212 [if African American (AA)] - Creatinine clearance estimated by 24-hr urine collection for creatinine clearance 6. Documented Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 7. Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment 8. Willing and able to provide written informed consent Exclusion Criteria At the time of Screening, participants who meet any of the following criteria will be excluded from participating in the study: 1. Patients with T315I mutation will not be excluded, but their response will be analyzed separately. --- T315I ---



HPO Nodes


HPO:
Acute megakaryocytic leukemia
Genes 1
GATA1
Acute myeloid leukemia
Genes 29
MPL MLF1 NSD1 JAK2 KRAS NPM1 ELANE DKC1 ETV6 TCIRG1 DNAJC21 SRP54 EFL1 FLT3 NUP214 CEBPA THPO MLLT10 RUNX1 PIGA CBFB BRCA2 KIT PICALM SBDS GFI1 SH3GL1 LPP DNMT3A
Chronic myelogenous leukemia
Genes 5
MPL BCR JAK2 KIT THPO
Leukemia
Genes 125
MPL RNASEH2B KRAS NPM1 TET2 MYD88 TSR2 RPL26 RPL27 TREX1 EFL1 PIGL SCN11A FLT3 PMS2 RPL35A EVC2 ABL1 CEBPA RARA NRAS WAS WIPF1 ATRX SH2B3 PDGFRA RB1 RNASEH2A PDGFRB CALR ARHGAP26 SH3GL1 RPS7 RPS10 NUMA1 GATA1 GATA2 RPS15A APC NSD1 ETV6 TCIRG1 DNAJC21 EVC SRP54 RPS17 NBN RPS19 SAMHD1 MSH2 RPS24 NUP214 RPS26 RPS27 RPS28 RPS29 MLLT10 RUNX1 XRCC4 CBFB CBL BCR ADAR TRIP13 ADA2 NSUN2 CREBBP PICALM GFI1 F13A1 F13B FANCA FANCC BLM FANCD2 FANCE NUTM1 JAK2 IFIH1 TYROBP MSH6 FANCG LIG4 PTPN11 SAMD9L THPO NF1 STS PIGA BRCA2 DYNC2LI1 PIK3CA SBDS GLI1 PIK3R1 BRD4 SETBP1 RNASEH2C LPP BUB1 BUB1B SCN9A SCN10A TREM2 MLF1 MLH1 ELANE DKC1 ATM HAX1 RPL35 GNB1 BUB3 CEP57 TAL1 KIT TAL2 RPL5 EP300 TP53 RPL11 KIF11 RPL15 DNMT3A RPL18
Myelodysplasia
Genes 68
FANCC MPL RAD51 FANCD2 RAD51C FANCE JAK2 TET2 RAF1 GFI1B FANCB FANCF FANCG LIG4 ASXL1 EFL1 PTPN11 BRIP1 ERCC4 SAMD9 THPO SF3B1 PIGA BRCA1 BRAF UBE2T ATRX BRCA2 SH2B3 TINF2 CALR SBDS FANCI NBEAL2 RECQL4 BUB1 BUB1B GATA2 RPS14 ELANE DKC1 TCIRG1 DNAJC21 SRP54 SMARCD2 SRP72 RPS19 FANCL HAX1 MAD2L2 XRCC2 RUNX1 BUB3 FANCM TERC CEP57 TRIP13 KIT TERT GINS1 GFI1 SLX4 HSPA9 PALB2 NAGS TP53 RFWD3 FANCA
Myeloid leukemia
Genes 12
GATA2 F13A1 CBL ARHGAP26 F13B KRAS PTPN11 SAMD9L KIT SETBP1 NF1 NRAS