Clinical Trials /

Clinical Trial of BP1001(Liposomal Grb2 Antisense Oligonucleotide) in Combination With Decitabine in AML / High Risk MDS

NCT02781883

Description:

The primary objective of this study is to assess whether the combination of BP1001 and decitabine provides greater efficacy (Complete Remission [CR], Complete Remission with incomplete hematologic recovery [CRi], Complete Remission with partial hematologic recovery [CRh], than decitabine alone (by historical comparison) in participants with AML/High Risk MDS that cannot or elect not to be treated with more intensive chemotherapy. The historical comparison to be used will be defined in the Statistical Analysis Plan (SAP) prior to database closure.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of BP1001 (Liposomal Grb2 Antisense Oligonucleotide) in Combination With LDAC in Patients With Previously Untreated AML
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: BP1001-201-AML
  • NCT ID: NCT02781883

Conditions

  • Acute Myeloid Leukemia (AML)

Interventions

DrugSynonymsArms
BP1001 in combination with LDACLiposomal Grb-2, L-Grb-2, Low dose Cytarabine, Low dose ara-CBP1001 + LDAC

Purpose

The primary objective of this study is to assess whether the combination of BP1001 and 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. Safety, pharmacokinetics, overall survival, time to response, and duration of response will also be studied.

Detailed Description

      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.

      Low-dose cytarabine (Ara-C) (LDAC) has been used in a variety of schedules in several Phase
      II trials in AML showing responses that include complete remission of disease. It is
      generally well tolerated and can be given in an outpatient or home care setting. Researchers
      hope that the combination of BP1001 and LDAC will result in greater response rates and
      duration of response in participants with AML that cannot or elect not to be treated with
      more intensive chemotherapy.

      This is a Phase IIa, multicenter, study of BP1001 in combination with LDAC in participants
      with previously untreated AML who are not otherwise eligible for standard or high-intensity
      chemotherapy regimens or who have elected a low-intensity regimen.

      This trial will utilize a single arm, open label, two-stage design to assess the safety
      profile, PK, PD, and efficacy of 60 mg/m2 of BP1001 in combination with LDAC compared to
      historical response rates documented for LDAC alone.

      Approximately 54 evaluable participants will receive the combination of BP1001 and LDAC.
    

Trial Arms

NameTypeDescriptionInterventions
BP1001 + LDACExperimentalBP1001 in combination with LDAC
  • BP1001 in combination with LDAC

Eligibility Criteria

        Inclusion Criteria:

          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:

               -  Newly diagnosed de novo AML; or

               -  Untreated secondary AML, including AML that has progressed from myelodysplastic
                  syndrome (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, performance status,
             co-morbidities, organ dysfunctions, or patient election of low-intensity treatment.

          6. Eligible for LDAC therapy, based on Investigator assessment

          7. Adequate hepatic and renal functions as defined by:

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

               -  Total bilirubin ≤1.5 times ULN; and

               -  Estimated glomerular filtration rate (eGFR) of at least 50ml/min using the
                  Cockcroft Gault formula will be determined at base line when testing of BUN and
                  creatinine is performed. The combination of eGFR serum creatinine and BUN will be
                  used to evaluate renal function and assure the safety of this patient function.

          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. Willing and able to provide written informed consent

        Exclusion Criteria:

          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 for any reason
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Assessment of efficacy by bone marrow aspirate or biopsy
Time Frame:180 days
Safety Issue:
Description:Complete Remission [CR], Complete Remission with incomplete hematologic recovery [CRi], Complete Remission with incomplete platelet recovery [CRp]) than LDAC alone (by historical comparison)

Secondary Outcome Measures

Measure:Evaluate safety and toxicity of the combination of BP1001 with LDAC using non-hematologic and hematologic measures per NCI CTCAE criteria
Time Frame:30 days
Safety Issue:
Description:
Measure:Evaluate the in vivo PK using plasma to compute half life and elimination.
Time Frame:30 days
Safety Issue:
Description:
Measure:Assess time to response from administration of BP1001+LDAC to CR, CRi, or CRp
Time Frame:30 days
Safety Issue:
Description:
Measure:Assess duration of response from day of response to day of disease progression
Time Frame:30 days
Safety Issue:
Description:
Measure:Assess overall survival from date of study entry to study closure or death
Time Frame:180 days
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bio-Path Holdings, Inc.

Trial Keywords

  • Liposomal Grb-2 treatment of AML
  • Liposomal Grb-2 with LDAC for AML

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