Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

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Brief Title

Trebananib With or Without Low-Dose Cytarabine in Treating Patients With Acute Myeloid Leukemia

Official Title

A Phase lb Study of the Safety, Feasibility, and Pharmacokinetics of AMG 386 Alone and in Combination With Low Dose Cytarabine in Acute Myeloid Leukemia (AML) Patients

Brief Summary

      This phase I trial studies the side effects and the best dose of trebananib when given
      together with or without low-dose cytarabine in treating patients with acute myeloid leukemia
      (AML). Trebananib may stop the growth of AML by blocking blood flow to the cancer. Drugs used
      in chemotherapy, such as cytarabine, work in different ways to stop the growth of cancer
      cells, either by killing the cells or by stopping them from dividing. Giving trebananib
      together with cytarabine may be an effective treatment for patients with AML.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To evaluate the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD)
      profile of AMG 386 (trebananib) when administered alone and in combination with low-dose
      cytarabine in adult patients with: untreated AML considered ineligible for standard induction
      chemotherapy; refractory and/or relapsed AML following at least one cycle of prior therapy
      who are not currently eligible for stem cell transplantation.

      SECONDARY OBJECTIVES:

      I. To evaluate clinical responses in AML patients following AMG 386 therapy alone or in
      combination with low-dose cytarabine therapy.

      II. To characterize the biological changes occurring in AML patients treated with AMG 386
      alone or in combination with low-dose cytarabine, specifically: alteration in angiopoietin
      (Ang)1, Ang2, Tie2, vascular endothelial growth factor (VEGF), and VEGF receptor (VEGFR)
      expression; changes in bone marrow vascularization and hypoxia; changes in gene and/or micro
      ribonucleic acid (microRNA) expression; PK/PD modeling to characterize the time course of AMG
      386 concentrations in relation to target inhibition and hematological response.

      III. To determine whether the above biological changes correlate with and/or predict for
      clinical response in AML patients treated on this study.

      OUTLINE: This is a dose-escalation study of trebananib. Patients are assigned to 1 of 2
      treatment arms.

      ARM A: Patients receive trebananib intravenously (IV) over 30-60 minutes on days 1, 8, 15,
      and 22.

      ARM B: Patients receive trebananib as in Arm A. Patients also receive cytarabine
      subcutaneously (SC) twice daily (BID) on days 1-14 of course 1 and days 1-7 of each
      subsequent course.

      In both arms, treatment repeats every 28 days* for up to 12 courses in the absence of disease
      progression or unacceptable toxicity.

      NOTE: *Course 1 is 35 days.

      After completion of study treatment, patients are followed up for 30 days, every month for 1
      year, every 3 months for 1 year, and then every 6 months for 3 years.
    

Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

Safety of trebananib when administered alone and in combination with low-dose cytarabine measured by number of participants with toxicities according to CTCAE

Secondary Outcome

 Clinical response in AML patients following trebananib therapy alone or given in combination with low-dose cytarabine therapy

Condition

Adult Acute Megakaryoblastic Leukemia (M7)

Intervention

trebananib

Study Arms / Comparison Groups

 Arm A (trebananib)
Description:  Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

24

Start Date

October 31, 2011

Completion Date

August 3, 2016

Primary Completion Date

September 24, 2013

Eligibility Criteria

        Inclusion Criteria:

          -  Diagnosis of AML as defined by the World Health Organization (excluding acute
             promyelocytic leukemia and chronic myeloid leukemia- blast/accelerated phase) in an
             adult patient

               -  Patients with newly diagnosed untreated AML for whom the treatment of choice is
                  low-intensity therapy by investigator assessment or who has declined intensive
                  induction therapy recommended by the investigator OR

               -  Patients with refractory or relapsed AML following at least one prior treatment
                  course who are not currently considered eligible for stem cell transplantation at
                  the time of screening due to non-optimal AML disease control, lack of suitable
                  transplantation donor, failure to meet other transplantation criteria, or refusal
                  to undergo transplantation

          -  Eastern Cooperative Oncology Group (ECOG) status 0-2 (ECOG 3 is excluded)

          -  Total bilirubin within normal institutional limits

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and
             alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 x
             institutional upper limit of normal (ULN)

          -  Creatinine clearance > 40ml/min per 24 hour urine collection or calculated according
             to the Cockcroft-Gault formula

          -  Urinary protein quantitative value of less than 30mg/dL in urine analysis or less than
             1+ on dipstick, unless quantitative protein is < 1000mg in a 24 hour urine sample

          -  Partial thromboplastin time (PTT) or activated (aPTT) =< 1.5 x ULN per institution
             laboratory range and international normalized ratio (INR) =< 1.5

          -  Patient or legal representative must understand the investigational nature of this
             study and sign an Independent Ethics Committee/Institutional Review Board approved
             written informed consent form prior to receiving any study related procedure

          -  Individuals of childbearing potential must agree to use acceptable contraceptive
             methods (e.g., double barrier) during treatment

        Exclusion Criteria:

          -  History of central nervous system involvement with leukemia

          -  History of venous or arterial thromboembolism within 12 months prior to enrollment

          -  History of clinically significant bleeding within 6 months of enrollment

          -  Unresolved toxicities from prior systemic therapies that are Common Terminology
             Criteria for Adverse Events (CTCAE) version 4 >= Grade 2 in severity except alopecia
             excluding hematological toxicities attributable to underlying disease

          -  Currently or previously treated with AMG 386, or other molecules that inhibit the
             angiopoietins or Tie2 receptor

          -  Current or within 30 days prior to enrollment treatment with immune modulators such as
             systemic cyclosporine or tacrolimus

          -  Has not yet completed a 14 day washout period for any previous anti-cancer systemic
             therapies (30 days for prior bevacizumab) with the exception of hydroxyurea or
             leukapheresis for uncontrolled leukocytosis

          -  Enrolled in or has not yet completed at least 14 days since ending other
             investigational device or drug trials, or currently receiving other investigational
             treatments

          -  Clinically significant cardiovascular disease within 12 months prior to enrollment,
             including myocardial infarction, unstable angina, grade 2 or greater peripheral
             vascular disease, cerebrovascular accident, transient ischemic attack, congestive
             heart failure, or arrhythmias not controlled by outpatient medication or placement of
             percutaneous transluminal coronary angioplasty/stent

          -  Major surgery within 28 days prior to enrollment or still recovering from prior
             surgery

          -  Minor surgical procedures, placement of tunneled central venous access device within 3
             days prior to enrollment

          -  Uncontrolled hypertension as defined as diastolic > 90mmHg OR systolic > 140mmHg; the
             use of anti-hypertensive medication to control hypertension is permitted

          -  Non-healing wound, ulcer (including gastrointestinal) or fracture

          -  Active uncontrolled infection, including human immunodeficiency virus (HIV) and active
             hepatitis infection

          -  Subject not consenting to the use of highly effective contraceptive, e.g., double
             barrier method (i.e., condom plus diaphragm) precautions during the course of the
             study and for 6 months after administration of the last study medication

          -  Subject has known sensitivity to any of the products to be administered during dosing

          -  History of allergic reactions to bacterially produced proteins

          -  Subject has previously been enrolled onto this study

          -  Subject will not be available for follow-up assessment

          -  Pregnant or nursing female patients

          -  Active second malignancy other than AML which is not in remission and/or for which the
             patient is currently receiving treatment

          -  Subject has any kind of disorder that compromises the ability of the subject to give
             written informed consent and/or to comply with study procedures

          -  Any condition which in the investigator's opinion makes the patient an unsuitable
             candidate for study participation
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Eunice Wang, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01555268

Organization ID

I 186010

Secondary IDs

NCI-2011-02979

Responsible Party

Sponsor

Study Sponsor

Roswell Park Cancer Institute

Collaborators

 National Cancer Institute (NCI)

Study Sponsor

Eunice Wang, Principal Investigator, Roswell Park Cancer Institute


Verification Date

February 2017