Clinical Trial of BP1001 (Liposomal Grb2 Antisense Oligonucleotide) in Combination With Dasatinib in Patients With Ph + CML Who Have Failed TKI, Ph+ AML, Ph+ MDS

NCT02923986 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: BP1001-202-CML
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Myelogenous Leukemia, Ph1-Positive; Acute Myeloid Leukemia; Myelodysplastic Syndrome

Keywords

Liposomal Grb-2 treatment of Ph+ CML; Liposomal Grb-2 with Das for Ph+ CML; Liposomal Grb-2 treatment of Ph+ AML; Liposomal Grb-2 with Das for Ph+ AML; Liposomal Grb-2 treatment of Ph+ MDS; Liposomal Grb-2 with Das for Ph+ MDS

Outcome Measures

Primary Outcomes (5)

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

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

  240 days

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

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

  240 days

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

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

  240 days

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

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

  240 days

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

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

  240 days

Secondary Outcomes (12)

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

  30 days

• 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

  240 days

• 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

  240 days

• 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

  240 days

• In vivo PK using plasma to compute half life and elimination

  30 days

Study Arms (2)

BP1001 (varying dose) + Dasatinib

EXPERIMENTAL

Phase 1b: BP1001 (varying dose levels) in combination with Das

Drug: BP1001 (varying dose); Drug: Dasatinib

BP1001 (fixed dose) + Dasatinib

EXPERIMENTAL

Phase IIa: BP1001 (fixed dose based on Phase 1b) in combination with Das

Drug: BP1001 (fixed dose); Drug: Dasatinib

Interventions

BP1001 (varying dose) DRUG

BP1001 (varying dose)

Also known as: Liposomal Grb-2, L-Grb-2

BP1001 (varying dose) + Dasatinib

BP1001 (fixed dose) DRUG

BP1001 (fixed dose)

Also known as: Liposomal Grb-2, L-Grb-2

BP1001 (fixed dose) + Dasatinib

Dasatinib DRUG

Dasatinib

Also known as: Das

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At the time of Screening, participants must meet all of the following criteria to be considered eligible to participate in the study:
• Adults ≥18 years of age
• Females must be of non-childbearing potential, surgically sterile, postmenopausal, or practice adequate methods of contraception during the study and for 30 days after the last dose of study drug or dasatinib
• Males must agree to use an adequate method of contraception during the study and for at least 30 days after the last dose of study drug or dasatinib
• Histologically documented diagnosis of Ph+ CML including chronic phase patients who have failed initial TKI therapy, accelerated or blast phase, Ph+ AML or High-risk Ph+ MDS.
• Ph+ chronic phase CML patients who are resistant to 1 or more TKIs, including dasatinib. Dasatinib-resistant patients can enroll in the Phase Ib portion of the study but are excluded from the Phase IIa portion of the study.
• One of the following parameters is required to meet criteria for accelerated CML:
• Blasts in Peripheral Blood or Bone Marrow ≥15%
• Promyelocytes and Blasts in Peripheral Blood or Bone Marrow ≥30%
• PB or BM basophils ≥20%
• Thrombocytopenia \<100 x 103/ml, not resulting from therapy
• Cytogenetic clonal evolution CML blast phase is defined as ≥30% blasts in peripheral blood or bone marrow, or presence of extramedullary disease, except for liver or spleen.
• AML/MDS
• Ph+ AML is defined as:
• Ph+ and meets diagnostic criteria for AML

You may not qualify if:

• At the time of Screening, participants who meet any of the following criteria will be excluded from participating in the study:
• Patients with T315I mutation will not be excluded, but their response will be analyzed separately.
• Another primary malignancy other than CML, AML, or MDS within the past 2 years except non-melanoma skin cancer, or carcinoma in situ of the cervix.
• Known, active leptomeningeal leukemia requiring intrathecal therapy. NOTE: Patients with a history of CNS disease may be allowed to participate based on at least 2 consecutive documented, negative spinal fluid assessment prior to Screening
• Isolated extramedullary leukemia without also meeting bone marrow criteria for acute leukemia (i.e., ≥20% blasts in bone marrow aspirate)
• Receipt of any anti-cancer therapy within 14 days of starting BP1001, with the exception of hydroxyurea or anagrelide, or TKI (within 2 days)
• Uncontrolled active, untreated, or progressive infection
• Receipt of any investigational agent within 14 days or 5 half-lives of starting BP1001
• Females who are pregnant, test positive for pregnancy, or are breast-feeding during the Screening period, or intend to become pregnant or breast-feed during the course of the study or within 30 days after last dose of study drug
• Prior exposure to BP1001
• Patients with a history of intolerance to dasatinib or for whom dasatinib may not be appropriate
• Serious intercurrent medical or psychiatric illness which, in the opinion of the Investigator, would interfere with the ability of the participant to complete the study
• Known active or clinically significant hepatitis B infection (based on positive surface antigen \[HBsAg\]), hepatitis C infection (based on positive antibody \[HCV Ab\]), or human immunodeficiency virus (HIV-1 or HIV-2, based on positive antibody)
• Presence of concurrent conditions that, in the opinion of the Investigator and/or Medical Monitor, may compromise the participant's ability to tolerate study treatment or interfere with any aspect of study conduct or interpretation of results. This includes but is not limited to, unstable or uncontrolled angina, New York Heart Association (NYHA) class III or IV congestive heart failure, uncontrolled and sustained hypertension, clinically significant cardiac dysrhythmia or clinically significant ECG abnormality (e.g., QTcF \>470 msec)
• Has had any of the following: clinically significant pleural effusion within 2 months, myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack within 6 months.

Sponsors & Collaborators

• Bio-Path Holdings, Inc.: lead

Study Sites (1)

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Dasatinib; amsonic acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• Maro Ohanian, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2016
• First Posted: October 5, 2016
• Study Start: September 1, 2017
• Primary Completion: May 27, 2020
• Study Completion: May 27, 2020
• Last Updated: May 28, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)