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

At the time of Screening, participants must meet all of the following criteria to be considered eligible to participate in the study:

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 dasatinib

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 dasatinib

4. 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

o Myeloid blasts ≥20 % or presence of AML-defining recurrent cytogenetic abnormality.

Ph+ high-risk MDS defined as:

• Ph+ high risk MDS ≥10% myeloid blasts or IPSS ≥intermediate-2

5. Adequate hepatic and renal functions as defined by:

1. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 times the upper limit of normal (ULN); and

2. Total bilirubin ≤1.5 times ULN; and

3. Estimated glomerular filtration rate (eGFR) of at least 40 ml/min. These estimations can be calculated using any of the following methods (Appendix D):

i. Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation

* GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 \[if female\] × 1.159 \[if black\] ii. Cockcroft gault equation

* Cockcroft Gault equation utilizing the TBW (Total body weight) to calculate an estimated creatinine clearance iii. CrCl = \[(140 - age) x TBW\] / (Scr x 72) x 0.85 \[if female\]

* Modification of Diet in Renal Disease (MDRD) Study equation iv. GFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × 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

What this study is about