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Report for Clinical Trial NCT02923986

Developed by Shray Alag, 2020.
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: Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Preleukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive Myelodysplastic Syndromes
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 (fixed dose) + Dasatinib BP1001 (varying 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 50
KIT DDX41 SBDS LPP ETV6 DNMT3A TERT JAK2 NUP214 CEBPA BRCA2 TCIRG1 DNAJC21 TET2 FLT3 TET2 JAK2 SRP54 SF3B1 SRP54 SH3GL1 KRAS EFL1 PIGA MLLT10 SRP54 DNAJC21 DKC1 RUNX1 RUNX1 MPL CBFB NSD1 THPO ELANE NPM1 ASXL1 CHIC2 MLF1 DNAJC21 ERBB3 GFI1 GFI1 SRSF2 KIT PICALM RPS14 GATA2 SBDS TET2
Chronic myelogenous leukemia
Genes 9
KIT MPL ASXL1 TET2 ABL1 JAK2 THPO BCR SRSF2
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Myelodysplasia
Genes 93
NAGS MPL SLX4 TET2 TERT TRIP13 DDX41 SBDS TP53 ATRX TET2 SF3B1 BUB1B TCIRG1 DNAJC21 RFWD3 BUB1 TET2 FANCL ATRX ASXL1 TET2 JAK2 SAMD9 SRP54 RPS14 PALB2 GINS1 SMARCD2 GATA2 SF3B1 BUB3 GATA2 SRP54 TET2 FANCB FANCE TET2 FANCM RFWD3 EFL1 RAD51 PIGA SRP54 DNAJC21 RAF1 DKC1 MPL RUNX1 MPL FANCD2 BRAF LIG4 FANCG RECQL4 THPO NBEAL2 CALR JAK2 TERC ERCC4 FANCI ELANE GATA2 SRP72 FANCG ASXL1 FANCC BRCA1 ERBB3 PTPN11 BRIP1 GFI1 SRSF2 HSPA9 KIT HAX1 GFI1B MAD2L2 CEP57 RPS14 FANCF SH2B3 XRCC2 RPS19 TINF2 SBDS TET2 BRCA2 RAD51C UBE2T JAK2 FANCA
Myeloid leukemia
Genes 20
KIT SETBP1 NF1 ARHGAP26 CBL TET2 KRAS PTPN11 F13A1 SAMD9L SAMD9L GATA2 CBL ASXL1 DNMT3A F13B NRAS SRSF2 TERC TERT