The primary objective of the Phase 1b study is to determine the dose-limiting toxicity (DLT)
and maximal tolerated dose (MTD) of BP1001 and Dasatinib (Das) in patients with Philadelphia
chromosome positive (Ph+) Chronic Myelogenous Leukemia (CML) in accelerated or blast phase.
The primary objective of the Phase IIa study is to assess the efficacy of the combination of
BP1001 and Das in patients with Ph+ CML.
The Grb2 gene has been mapped to the human chromosome region 17q22-qter, a region that is
duplicated in leukemias and solid tumors, which may result in an increased copy number of the
Grb2 gene product. As Grb2 is important for the transformation of murine hematopoietic cells,
and the proliferation of human leukemia cells that express high levels of oncogenic tyrosine
kinases, inhibition of Grb2 may have a significant impact on the natural history of
leukemias. The study drug (BP1001) may be able to inhibit the cells from making Grb-2.
Researchers hope that without this protein, the leukemia cells will die.
Dasatinib (Das) has been a well established therapeutic regimen in the treatment of Ph+ CML
patients who are in accelerated of blast phase. Researchers hope that the combination of
BP1001 and Das will provide a benefit to CML patients in accelerated or blast phase, who
typically do not respond to the front-line treatment, imatinib.
This is a Phase Ib/IIa, multicenter, study of BP1001 in combination with Das in participants
with Ph+ CML who are in accelerated or blast phase.
This trial will utilize a single arm, open label design to assess the safety profile, DLT,
MTD, PK, and efficacy of BP1001 in combination with Das.
Phase Ib portion of the study: The Phase Ib study employs an open-label, sequential,
dose-escalation design to assess safety, tolerability and toxicity, tumor response and
A standard "3+3" design will be used in which successive cohorts of patients with CML are
being treated with BP1001 at the MTD (or highest tested dose [HTD] if the MTD is not defined)
and 1 level below the MTD (or HTD) in combination with a fixed dose of Das to characterize
safety and biological effect, as well as identify the recommended Phase IIa dose.
Phase IIa portion of the study: The Phase IIa study is an open-label, single-dose level
study. All participants who are eligible to receive treatment on study will receive the same
dose level for both BP1001 (the HTD or 1 level below the HTD) as determined by the Phase Ib
study and Das (140 mg). There will be no randomization for this study. The Phase IIa study
will compare the efficacy of the BP1001 in combination with Das to historical response rates
documented for Das alone, and will evaluate the PK of BP1001, when given alone or in
combination with Das.
Approximately 40 evaluable participants will receive the combination of BP1001 with Das in
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 Das
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 Das
4. Histologically documented diagnosis of Ph+ CML, in accelerated or blast phase.
One of the following parameters is required to meet criteria for accelerated CML:
- Blasts in Peripheral Blood or Bone Marrow ≥15% (either myeloid or lymphoid
- 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 Blast phase is defined as ≥30% blasts in peripheral
blood or bone marrow, or presence of extramedullary disease, except for liver or
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 50 ml/min; the Cockcroft
Gault formula will be utilized to determine eGFR when blood urea nitrogen (BUN)
and creatinine testing are performed at baseline. The combination of eGFR serum
creatinine and BUN will be used to evaluate patient's renal function for safety
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
1. Patients with T315I mutation will not be excluded, but their response will be analyzed
2. Another primary malignancy other than CML within the past 2 years except non-melanoma
skin cancer, or carcinoma in situ of the cervix.
3. 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
4. Isolated extramedullary leukemia without also meeting bone marrow criteria for
5. Receipt of any anti-cancer therapy within 14 days of starting BP1001, with the
exception of hydroxyurea or anagrelide, or TKI (within 2 days)
6. Uncontrolled active, untreated, or progressive infection
7. Receipt of any investigational agent within 14 days or 5 half-lives of starting BP1001
8. 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
9. Prior exposure to BP1001
10. Patients with a history of intolerance to Das or for whom Das might not be appropriate
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
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. 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)
14. Within the past 6 months, has had any of the following: pleural effusion, myocardial
infarction, unstable angina pectoris, coronary/peripheral artery bypass graft,
cerebrovascular accident or transient ischemic attack
15. Uncontrolled seizure disorder (ie, seizures within the past 2 months).
16. Unable or unwilling to communicate or cooperate with the Investigator or follow the
protocol for any reason