A Phase IIa Single-arm, Open-label, Two-stage Clinical Trial to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of BP1001 (a Liposomal Grb2 Antisense Oligonucleotide) in Combination with Low-dose Cytarabine (LDAC) in Patients with Previously Untreated Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Induction Therapy
The goal of this clinical research study is to learn if combining BP1001 with the standard-of-care drug cytarabine can help control the disease in patients with AML.
Disease Group: Other diseases of blood and blood-forming organs
Treatment Agent: BP-100-1.01
Treatment Location: Both at MD Anderson & Other Sites
Sponsor: Bio-Path Holdings, Inc.
Primary Objective The primary objective of this study is to assess whether the combination of BP1001 and low dose cytarabine (LDAC) provides greater efficacy (Complete Remission [CR], Complete Remission with incomplete hematologic recovery [CRi], Complete Remission with incomplete platelet recovery [CRp]) than LDAC alone (by historical comparison) in participants with AML that cannot or elect not to be treated with more intensive chemotherapy. Secondary Objectives The following are secondary objectives of this study: · To assess the safety of BP1001 in combination with LDAC · To evaluate the pharmacokinetics (PK) of BP1001 when given alone and in combination with LDAC · To assess time to response, overall survival, and duration of response Exploratory Objective The exploratory objective of this study will evaluate the correlation of treatment response with cytogenetic and molecular characteristics.
IRB Review and Approval Date: 03/13/2017
Recruitment Status: Open
Projected Accrual: 56 (from up to 12 sites in the United States, including MD Anderson)
1) Adults >/= 18 years of age
2) 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 LDAC
3) 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 LDAC
4) Histologically documented diagnosis (based on the 2008 World Health Organization [WHO] Classification) of one of the following: a. Newly diagnosed de novo AML; or b. Untreated secondary AML, including AML that has progressed from MDS
5) Investigator considers participant ineligible for intensive induction therapy based on medical reasons, disease characteristics such as genetics, type of AML (de novo or secondary), or participant characteristics such as age, presence of a second malignancy requiring treatment, known central nervous system leukemia, clinically relevant QT prolongation (ie, long QT syndrome; QTcF >=/ 470 ms), inadequate organ function (bilirubin >=/ 1.5 mg/dL, aspartate aminotransferase or alanine aminotransferase >=/ 2.5-fold the upper limit of normal, serum creatinine >=/ 2.0 mg/dL), concomitant intercurrent illness that could compromise the evaluation of efficacy or safety of the trial drug (eg, active severe infection, unstable angina pectoris, severe cardiac insufficiency), and psychiatric illness or social situation that would limit compliance with trial requirements.
6) Eligible for LDAC therapy, based on Investigator assessment
7) Adequate hepatic and renal functions as defined by: a. Aspartate transaminase (AST) and alanine transaminase (ALT)<=/2.5 times the upper limit of normal (ULN); and b. Total bilirubin<=/1.5 times ULN; and c. Serum creatinine <=/3 times ULN
8) Documented Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
9) Recovered from the effects of any prior surgery, radiotherapy, or antineoplastic treatment (with the exception of alopecia), based on Investigator assessment
10) Able to understand and sign the IRB-approved informed consent document for this trial
1) Active non-hematologic or lymphoid malignancy other than AML treated
with immuno- or chemotherapy within the previous 12 months except active
non-melanoma, non-invasive skin cancer will be allowed.
2) Known, active leptomeningeal leukemia requiring intrathecal therapy. NOTE: Patients with a history of CNS disease may be allowed to participate based on at least 1 documented, negative spinal fluid assessment within 28 days prior to Screening
3) Isolated extramedullary leukemia without also meeting bone marrow criteria for acute leukemia (ie, >/=20% blasts in bone marrow aspirate)
4) Acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) PML-RARA
5) Chronic myeloid leukemia (CML) in any phase
6) Receipt of any anti-cancer therapy within 14 days prior to C1D1, with the exception of hydroxyurea or anagrelide (within 24 hours), TKI (within 1days), or a single dose of cytarabine (for proliferative disease)
7) Uncontrolled active, untreated, or progressive infection
8) Receipt of any investigational agent or study treatment within 30 days prior to C1D1
9) 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
10) Prior exposure to BP1001
11) 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
12) Active/chronic 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)
13) History of any serious adverse reaction or hypersensitivity to cytarabine, unless reaction is deemed irrelevant to the study by the Investigator and Medical Monitor
14) 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 (eg, QTcF >470 msec)
15) Within the past 6 months, has had any of the following: myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass graft, cerebrovascular accident or transient ischemic attack
16) Uncontrolled seizure disorder (ie, seizures within the past 2 months).
17) Unable or unwilling to communicate or cooperate with the Investigator or follow the protocol.
Information and next steps
Other diseases of blood and blood-forming organs
For general questions about clinical trials: