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:

Completed

Phase:

Phase 1

Trial Eligibility

Document

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

  • ORG STUDY ID: 2003-0578 (v) 08-8
  • NCT ID: NCT01159028

Conditions

  • Recurrent Adult Acute Myeloid Leukemia
  • Acute Lymphoblastic Leukemia
  • Myelodysplastic Syndrome
  • Ph1 Positive CML

Interventions

DrugSynonymsArms
BP1001Liposomal Grb-2, L-Grb-2, BP-100-1.01BP1001
BP1001 in combination with LDACLiposomal Grb-2, L-Grb-2, BP-100-1.01, low dose ara-CBP1001 in combination with LDAC

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

NameTypeDescriptionInterventions
BP1001ExperimentalSubjects are treated with open-label study drug (BP1001) in a dose-escalation model.
  • BP1001
BP1001 in combination with LDACExperimentalAML 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.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety of BP1001
Time Frame:30 days
Safety Issue:
Description:Evaluate toxicity, tolerance, and MTD of escalating doses of BP1001

Secondary Outcome Measures

Measure:Optimal biologically active dose
Time Frame:30 days
Safety Issue:
Description:Determine the optimal biologically active dose of BP1001 defined as a 50% reduction in Grb-2 expression in circulating leukemia cells
Measure:In vivo pharmacokinetics
Time Frame:30 days
Safety Issue:
Description:Evaluate the in vivo PK of BP1001 in all subjects using plasma and urine to compute half life and elimination
Measure:Correlate PK data with historical experience
Time Frame:30 days
Safety Issue:
Description:Correlate the in vivo PK data with historical experience to demonstrate the liposomal delivery performs as expected for all subjects by comparing PK data (half life and elimination) obtained from each subject with historical experience

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Bio-Path Holdings, Inc.

Trial Keywords

  • Liposomal Grb-2 treatment of CML, AML, CLL, MDS
  • Liposomal Grb-2 with LDAC for AML

Last Updated

May 28, 2020