Clinical Trials /

Clinical Trial of BP1001 (L-Grb-2 Antisense Oligonucleotide) in CML, AML, ALL & MDS

NCT01159028

Description:

The first goal of this clinical research study is to find the highest safe dose of BP1001, a liposomal Growth Factor Receptor Bound Protein-2 antisense oligodeoxynucleotide (L-Grb2 AS), for patients with Philadelphia Chromosome positive CML, AML, ALL and MDS. The response of the leukemia to this treatment will also be studied. The second goal of this clinical research study is to evaluate the safety and toxicity of the combination of BP1001 and concurrent low-dose ara-C (LDAC) in patients with AML.

Related Conditions:
  • Chronic Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Clinical Trial of <span class="go-doc-concept go-doc-intervention">BP1001</span> (<span class="go-doc-concept go-doc-intervention">L-Grb-2</span> Antisense Oligonucleotide) in <span class="go-doc-concept go-doc-disease">CML</span>, <span class="go-doc-concept go-doc-disease">AML</span>, <span class="go-doc-concept go-doc-disease">ALL</span> & <span class="go-doc-concept go-doc-disease">MDS</span>

Title

  • Brief Title: Clinical Trial of BP1001 (L-Grb-2 Antisense Oligonucleotide) in CML, AML, ALL & MDS
  • Official Title: A Phase I Clinical Trial to Study the Safety, Pharmacokinetics, and Efficacy of BP1001 (L-Grb-2 Antisense Oligonucleotide) in Patients With Refractory or Relapsed Acute Myeloid Leukemia, Philadelphia Chromosome Positive Chronic Myelogenous Leukemia, or Acute Lymphoblastic Leukemia, and Myelodysplastic Syndrome
  • Clinical Trial IDs

    NCT ID: NCT01159028

    ORG ID: 2003-0578 (v) 08-8

    Trial Conditions

    Recurrent Adult Acute Myeloid Leukemia

    Acute Lymphoblastic Leukemia

    Myelodysplastic Syndrome

    Ph1 Positive CML

    Trial Interventions

    Drug Synonyms Arms
    BP1001 Liposomal Grb-2, L-Grb-2, BP-100-1.01 BP1001
    BP1001 in combination with LDAC Liposomal Grb-2, L-Grb-2, BP-100-1.01, low dose ara-C BP1001 in combination with LDAC

    Trial Purpose

    The first goal of this clinical research study is to find the highest safe dose of BP1001, a
    liposomal Growth Factor Receptor Bound Protein-2 antisense oligodeoxynucleotide (L-Grb2 AS),
    for patients with Philadelphia Chromosome positive CML, AML, ALL and MDS. The response of
    the leukemia to this treatment will also be studied. The second goal of this clinical
    research study is to evaluate the safety and toxicity of the combination of BP1001 and
    concurrent low-dose ara-C (LDAC) in patients with AML.

    Detailed Description

    The Philadelphia Chromosome is an unusual genetic trait found in 90-95% of patients with CML
    and approximately 20-25% of patients with ALL. The protein created by this unusual trait
    causes normal cells within the body to become cancer cells, and then causes these cells to
    grow and divide at a rapid rate. Researchers think that the protein "Growth Factor Receptor
    Bound Protein-2 (Grb-2)" plays an important role in the rapid growth of leukemic cells. 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.

    Up to 60 patients are expected to be enrolled on this study.

    Part A: Dose escalation: Each cohort will receive BP1001 at a dose higher than the previous
    group.

    Part B: Dose-expansion Cohorts: Subjects with relapsed or refractory AML will receive
    escalating doses of BP1001 concurrently with fixed low-dose ara-C (LDAC)

    The study drug is an antisense molecule complementary to the messenger RNA (mRNA) code for
    the cell's expression of the protein Grb-2. The study drug is incorporated into lipid (fat)
    particles known as liposomes. This incorporation process is part of the manufacturing
    process and is done before the study drug is administered. The liposomes (which carry the
    study drug) will be administered intravenously twice a week for 28 days. Subjects enrolled
    in Part B of the study will receive study drug twice a week for 28 days concurrently with
    low dose ara-C, self administered twice daily for 10 consecutive days.

    Trial Arms

    Name Type Description Interventions
    BP1001 Experimental Subjects are treated with open-label study drug (BP1001) in a dose-escalation model. BP1001
    BP1001 in combination with LDAC Experimental AML subjects are treated with open-label escalating study drug (BP1001) in combination with low dose ara-C (LDAC) BP1001 in combination with LDAC

    Eligibility Criteria

    Inclusion Criteria

    1. Male or female patients 18 years of age or older

    2. A diagnosis of refractory or relapsed AML, or Ph+ CML (in chronic, accelerated or
    blast phase, or acute lymphoblastic leukemia, or myelodysplastic syndrome.

    One of the following parameters is required to meet criteria for accelerated phase
    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

    Blast phase is defined as 30% blasts in peripheral blood or bone marrow, or presence
    of extramedullary disease, except for liver or spleen.

    3. Patients with CML must have demonstrated resistance and/or intolerance to therapy
    with at least 2 tyrosine kinase inhibitors (TKI)

    4. Patients with AML and ALL should have received at least 1 prior treatment regimen and
    either failed to achieve response or relapsed on treatment

    5. Patients with MDS should have failed prior therapy with a hypomethylating agent or,
    if associated with a 5q- chromosomal abnormality, lenalidomide. NOTE: Patients with
    5q- unable to receive or intolerant to lenalidomide are also eligible.

    6. Have clinically adequate hepatic and renal functions as defined by:

    - ALT<2x ULN

    - Serum creatinine concentration <2x ULN

    - Serum bilirubin <2x ULN

    7. Patients must sign an informed consent

    8. Women of childbearing age must have a negative serum or urine pregnancy test prior to
    the initiation of study drug.

    9. Barrier contraceptive precautions are to be used throughout the trial by all study
    participants of child bearing potential.

    10. Have not received anti-cancer therapy for at least 2 weeks prior to study entry, with
    the exception of low dose ara-C (LDAC) given as subcutaneous injections (no less than
    15 days prior), hydroxyurea or anagrelide (no less than 24 hours prior), TKI (no less
    than 5 days prior), and interferon (no less than 2 weeks prior)

    11. Have an ECOG Performance of 0-2

    12. Have a life-expectancy 3 months

    Exclusion Criteria

    1. Serious intercurrent medical illnesses which would interfere with the ability of the
    patient to carry out the treatment program

    2. Pregnant or breastfeeding women

    3. Patients who have uncontrolled active infection

    4. Patients who have received another investigational product within the longer of 14
    days or 5 half-lives of the previous product

    5. Any history of adverse reaction or hypersensitivity to LDAC

    Part B: BP1001 with Concurrent LDAC Dose-Expansion Cohorts

    Enrollment in the dose-expansion cohorts (DEC) will be limited to only those patients with
    a diagnosis of refractory or relapsed AML(except acute promyelocytic leukemia) or those
    who are refractory to at least 1 prior therapy regimen and no more than 1 prior salvage
    regimen.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 70 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Safety of BP1001

    Safety of BP1001 in combination with LDAC

    Secondary Outcome Measures

    Optimal biologically active dose

    In vivo pharmacokinetics

    Correlate PK data with historical experience

    Trial Keywords

    Liposomal Grb-2 treatment of CML, AML, CLL, MDS

    Liposomal Grb-2 with LDAC for AML