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Adult Acute Megakaryoblastic Leukemia (M7)Phase 1NCT01555268

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

A Phase 1 study testing trebananib, cytarabine and laboratory biomarker analysis in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Roswell Park Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
trebananib, cytarabine and laboratory biomarker analysis
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
2 sitesUnited States
Study dates
31 Oct 2011to 3 Aug 2016
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • University of Rochester

    Rochester, New York, 14642

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
trebananib, cytarabine, laboratory biomarker analysis, pharmacological study
Medical subject headings
Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Erythroblastic, Acute

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • trebananibBiological

    Also called AMG 386, AMG386

    Given IV

  • cytarabineDrug

    Also called ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U

    Given SC

  • laboratory biomarker analysisOther

    Correlative studies

  • pharmacological studyOther

    Also called pharmacological studies

    Correlative studies

Study groups in NCT01555268
Study groupRoleWhat they receive
Arm A (trebananib)ExperimentalPatients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22.
Receives: Biological: trebananib; Other: laboratory biomarker analysis; Other: pharmacological study
Arm B (trebananib, cytarabine)ExperimentalPatients receive trebananib as in Arm A. Patients also receive cytarabine SC BID on days 1-14 of course 1 and days 1-7 of subsequent courses.
Receives: Biological: trebananib; Drug: cytarabine; Other: laboratory biomarker analysis; Other: pharmacological study

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Adverse events will be tabulated overall and by arm.

    Measured: Up to 30 days after the last dose of study drug

  2. PK/PD profile of trebananib when administered alone

    A population PK/PD model will be developed to characterize the time course of AMG 386 concentrations in relation to target inhibition and hematological response. Model-predicted PK parameters will be generated, such as individual areas-under-the-curve (AUCs) and Cmax for AMG 386, to correlate with targeted biomarkers, such as Ang1, and Ang2, and VEGF as well as leukocyte count.

    Measured: Days 1, 3-5, 7, 8, 22, 24-26, and 29 of course 1

  3. PK/PD profile of trebananib when administered in combination with low-dose cytarabine

    A population PK/PD model will be developed to characterize the time course of AMG 386 concentrations in relation to target inhibition and hematological response. Model-predicted PK parameters will be generated, such as individual AUCs and Cmax for AMG 386, to correlate with targeted biomarkers, such as Ang1, and Ang2, and VEGF as well as leukocyte count.

    Measured: Days 1 and 7 of course 1

Secondary outcomes (5)

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

    Measured: Up to 5 years

  2. Alterations in Ang1, Ang2, Tie2, VEGF, and VEGFR expression

    Identified by flow cytometric analysis of peripheral blood and marrow aspirate cells.

    Measured: Up to 30 days post-treatment

  3. Changes in bone marrow vascularization and hypoxia

    Bone marrow vascularization will be assessed by cluster of differentiation (CD)31+ and/or CD34 microvessel staining as well as VEGF-A expression and hypoxia using hypoxia-inducible factor (HIF)-1alpha and/or CAIX immunohistochemistry.

    Measured: Baseline up to 30 days post-treatment

  4. Changes in gene and/or microRNA expression

    Microarray profiling for all human microRNAs will be performed on stored leukemia marrow cells and confirmed by real time-polymerase chain reaction (Q-PCR) analysis for specific microRNAs of interest.

    Measured: Baseline up to 30 days post-treatment

  5. Characterization of time course of trebananib concentrations in relation to target inhibition and clinical response using PK/PD modeling

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2012 (estimated)
  2. Study start31 Oct 2011
  3. Primary completion24 Sep 2013
  4. Study completion3 Aug 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01555268
Sponsor's protocol ID
I 186010
Other IDs
NCI-2011-02979
Status last verified
Sep 2022
First submitted
16 Feb 2012
Last updated
13 Sep 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing trebananib, cytarabine and laboratory biomarker analysis in people with Adult Acute Megakaryoblastic Leukemia (M7) and Adult Acute Minimally Differentiated Myeloid Leukemia (M0), run by Roswell Park Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of trebananib when administered alone and in combination with low-dose cytarabine measured by number of participants with toxicities according to CTCAE (time frame: Up to 30 days after the last dose of study drug). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01555268.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2022.

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