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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2010 by Bio-Path Holdings, Inc..
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Bio-Path Holdings, Inc.
ClinicalTrials.gov Identifier:
NCT01159028
First received: July 7, 2010
Last updated: July 8, 2010
Last verified: April 2010
  Purpose

The goal of this clinical research study is to find the highest safe dose of a liposomal Growth Factor Receptor Bound Protein-2 antisense oligodeoxynucleotide (L-Grb2 AS) that can be given as treatment for patients with Philadelphia Chromosome positive CML, AML, CLL and MDS. The trade name of this drug is BP-100-1.01. The response of the leukemia to this treatment will also be studied. In addition, the time needed for the body to process this drug will be evaluated.


Condition Intervention Phase
Safety and Pharmacokinetics of L-Grb-2 in Treating CML, AML, CLL and MDS
Drug: BP-100-1.01 (Liposomal Grb-2)
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial to Study the Safety, Pharmacokinetics, and Efficacy of BP-100.1.01 (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

Resource links provided by NLM:


Further study details as provided by Bio-Path Holdings, Inc.:

Primary Outcome Measures:
  • Safety [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Evaluate the patient tolerance to this cancer drug


Secondary Outcome Measures:
  • Efficacy [ Time Frame: 30 days ] [ Designated as safety issue: No ]
    Measure the reduction in leukemic blast cells


Estimated Enrollment: 18
Study Start Date: June 2010
Intervention Details:
    Drug: BP-100-1.01 (Liposomal Grb-2)
    5 mg/meter squared, dose is constituted in normal saline, administered by IV. Treatment given twice a week for four weeks.
    Other Names:
    • Liposomal Grb-2
    • L-Grb-2
Detailed Description:

The Philadelphia Chromosome is an unusual genetic trait found in 90-95% of patients with CML. 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) is necessary to the growth of these cancerous cells. The drug under study may be able to prevent the cells from making this protein. Researchers hope that without this protein, the leukemia cells will die.

Between 18 and 30 patients are expected to be enrolled on this study. Between 3 and 6 patients will be treated at each dose level. Each new group will be treated at a dose higher than the previous group. If the highest safe dose of the study drug is not found after the completion of this study, additional doses or another study may be considered.

The study drug is an antisense molecule complementary to the mRNA (messenger RNA) 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 procedure and is done before the drug is administered. The liposomes (which carry the study drug) will then be injected into a vein twice a week for at least 28 days.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 4.1.1 Male or female patients 18 years of age or older 4.1.2 A diagnosis of refractory or relapsed acute myeloid leukemia, 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.

4.1.2.1 Patients with CML must have demonstrated resistance and/or intolerance to therapy with at least 2 tyrosine kinase inhibitors (TKI) 4.1.2.2 AML and Ph+ ALL should have received at least one prior treatment regimen and either failed to achieve response or relapsed on treatment.

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

4.1.3 Patients must have clinically adequate hepatic and renal functions as defined by:

ALT<2x ULN Serum creatinine concentration <2x ULN Serum bilirubin <2x ULN 4.1.4 Patients must sign an informed consent. 4.1.5 Women of childbearing age must have a negative serum or urine pregnancy test prior to the initiation of study drug.

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

4.1.7 Patients must be off anti-cancer therapy for at least two weeks prior to study entry, with the exception of hydroxyurea or anagrelide (24 hours), TKI (5 days), and interferon (two weeks).

4.1.8 Patients with ECOG Performance of 0-2

Exclusion Criteria:

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

4.2.2 Pregnant or breastfeeding women 4.2.3 Patients who have uncontrolled active infection 4.2.4 Patients who have received another Investigational product within the longer of 14 days or 5 half-lives of the previous product.

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01159028

Contacts
Contact: Jorge Cortes, MD 713-794-5783 jcortes@mdanderson.org

Locations
United States, Texas
M. D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Jorge Cortes, MD         
Sponsors and Collaborators
Bio-Path Holdings, Inc.
Investigators
Study Chair: Jorge Cortes, MD M.D. Anderson Cancer Center
  More Information

No publications provided

Responsible Party: Peter Nielsen, President & CEO, Bio-Path Holdings, Inc.
ClinicalTrials.gov Identifier: NCT01159028     History of Changes
Other Study ID Numbers: 2003-0578 (v) 08-4
Study First Received: July 7, 2010
Last Updated: July 8, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by Bio-Path Holdings, Inc.:
Liposomal Grb-2 treatment of CML

ClinicalTrials.gov processed this record on September 22, 2014