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Trial record 1 of 2 for:    Liposomal Grb2 Antisense | AML
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Clinical Trial of BP1001 (Liposomal Grb2 Antisense Oligonucleotide) in Combination With LDAC in Patients With Previously Untreated AML

This study is currently recruiting participants.
See Contacts and Locations
Verified April 2017 by Bio-Path Holdings, Inc.
Sponsor:
Information provided by (Responsible Party):
Bio-Path Holdings, Inc.
ClinicalTrials.gov Identifier:
NCT02781883
First received: May 18, 2016
Last updated: April 21, 2017
Last verified: April 2017
  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.

Condition Intervention Phase
Acute Myeloid Leukemia (AML) Drug: BP1001 in combination with LDAC Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Assessment of efficacy by bone marrow aspirate or biopsy [ Time Frame: 180 days ]
    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:
  • 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 ]
  • Evaluate the in vivo PK using plasma to compute half life and elimination. [ Time Frame: 30 days ]
  • Assess time to response from administration of BP1001+LDAC to CR, CRi, or CRp [ Time Frame: 30 days ]
  • Assess duration of response from day of response to day of disease progression [ Time Frame: 30 days ]
  • Assess overall survival from date of study entry to study closure or death [ Time Frame: 180 days ]

Estimated Enrollment: 54
Study Start Date: May 2016
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BP1001 + LDAC
BP1001 in combination with LDAC
Drug: BP1001 in combination with LDAC
BP1001 in combination with LDAC
Other Names:
  • Liposomal Grb-2
  • L-Grb-2
  • Low dose Cytarabine
  • Low dose ara-C

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  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: NCT02781883

Contacts
Contact: Maro Ohanian, DO 713-792-2631 mohanian@mdanderson.org

Locations
United States, Kansas
University of Kansas Cancer Center Recruiting
Fairway, Kansas, United States, 66205
Contact: Kerry Hepler, RN    913-945-7552    khepler@kumc.edu   
Contact: Jecinta Scott, MS    913-945-7505    jscott11@kumc.edu   
Principal Investigator: Tara Lin, MD         
United States, New Jersey
New Jersey Hematology Oncology Associates Recruiting
Bricktown, New Jersey, United States, 08724
Contact: Apurv Agrawal, MD       agrawalmd@gmail.com   
United States, New York
Weill Cornell Medical College - New York - Presbyterian Hospital Recruiting
New York, New York, United States, 10021
Contact: Gail J Roboz, MD    646-962-2700    gar2001@med.cornell.edu   
Principal Investigator: Gail J Roboz, MD         
United States, Texas
University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Maro Ohanian, DO    713-792-2631    mohanian@mdanderson.org   
Principal Investigator: Maro Ohanian, MD         
Baylor Scott & White Research Institute Recruiting
Temple, Texas, United States, 76508
Contact: Niki Watson    254-724-2111    Niki.Watson@BSWHealth.org   
Contact: Dedra Preece    254-724-2111    Dedra.Preece@BSWHealth.org   
Principal Investigator: Kathleen Halka, MD         
Sub-Investigator: Christian T Cable, MD         
Sub-Investigator: Vinit G Karur, MD         
Sub-Investigator: Mark Holguin, MD         
Sub-Investigator: Rakesh Surapaneni, MD         
United States, West Virginia
West Virginia University/Mary Babb Randolph Cancer Center Recruiting
Morgantown, West Virginia, United States, 26506
Contact: Michael Craig, MD    304-293-0609    craigm@wvumedicine.org   
Sponsors and Collaborators
Bio-Path Holdings, Inc.
Investigators
Principal Investigator: Maro Ohanian, DO M.D. Anderson Cancer Center
  More Information

Responsible Party: Bio-Path Holdings, Inc.
ClinicalTrials.gov Identifier: NCT02781883     History of Changes
Other Study ID Numbers: BP1001-201-AML
Study First Received: May 18, 2016
Last Updated: April 21, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Bio-Path Holdings, Inc.:
Liposomal Grb-2 treatment of AML
Liposomal Grb-2 with LDAC for AML

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 21, 2017