1336GCC: Study of Erwinaze for Treatment of Acute Myeloid Leukemia (AML)

NCT02283190 | Completed Phase 1 DMC

• 1 other identifier: 1336GCC, HP-00056335
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Erwinaze will be administered intravenously at a dose of 25,000 IU/m2 (dose cohort 0) for 6 doses MWF over a period of 2 weeks to 9 patients (as described below and in the following schema). Blood counts, chemistries including bilirubin, amylase and lipase, and coagulation studies including fibrinogen will be measured and reviewed before each asparaginase dose. Fibrinogen (\<100 mg/dL) can be replaced with cryoprecipitate before each dose at the discretion of treating physician. Treatment will be stopped for elevation of amylase, lipase or direct bilirubin above normal range.

Conditions

Acute Myeloid Leukemia

Keywords

Asparaginase; Glutamine

Outcome Measures

Primary Outcomes (6)

• To determine the dose of Erwinase that produces a plasma glutamine level ≤120 μmol/L with an acceptable safety profile.

  The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.

  Day 3

• Efficacy of Erwinase doses as measured by plasma glutamine level

  The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.

  Day 5

• Efficacy of Erwinase doses as measured by plasma glutamine level

  The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.

  Day 8

• Efficacy of Erwinase doses as measured by plasma glutamine level

  The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.

  Day 10

• Efficacy of Erwinase doses as measured by plasma glutamine level

  The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.

  Day 12

• Efficacy of Erwinase doses as measured by plasma glutamine level

  The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.

  Day 42

Secondary Outcomes (4)

• Efficacy of Erwinase doses as measured by nadir serum asparaginase activity

  Days 3, 5,8,10,12, & 42

• Efficacy of Erwinase as measured by acute myeloid leukemia (AML) disease response

  Days 15 and 29

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  30 days from last dose of drug or until death, whichever occurs first

• Validity of serum and urine 2-hydroxyglutarate (2-HG) as a biomarker for AML with or without IDH mutation

  Days 0, 8, & 42

Study Arms (1)

Ewwinase

EXPERIMENTAL

Six doses of Erwinase given three times weekly (Monday-Wednesday-Friday) for two weeks. Possible dose levels used are 20.000 IU/m2/day, 25,000IU/m2/day, and 30,000IU/m2/day.

Drug: Erwinase

Interventions

Erwinase DRUG

Six doses of Erwinase, given Monday-Wednesday-Friday for 2 weeks. Dosage levels to be used are: 20,000 IU/ m2 /day, 25,000 IU/ m2 /day, 30,000 IU/ m2 /day.

Also known as: Asparaginase, Crisantaspase

Ewwinase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed AML
• years and older
• AML has relapsed after, or is refractory to, first-line therapy, with or without subsequent additional therapy
• Have received or are ineligible for immediate established curative regimens
• ASCT patients are eligible provided that they are \>= 4 weeks from stem cell infusion
• alloSCT patients are eligible if they are \>= 60 days post stem cell infusion, have no evidence of graft versus host disease (GVHD) \> Grade 1, and are \>= 2 weeks off all immunosuppressive therapy
• Previous cytotoxic chemotherapy completed at least 3 weeks and radiotherapy at least 2 weeks prior to day 1 of study treatment
• Biologic agents stopped at least 1 week prior to day 1 of study treatment
• DNA methyltransferase inhibitors stopped at least 3 weeks prior to day 1 of study treatment
• ECOG performance status ≤2
• Patients must have normal organ function
• Female patients of childbearing potential must have a negative pregnancy test.
• Ability to understand and willingness to sign a written informed consent document.

You may not qualify if:

• Patients receiving any other investigational agents, or concurrent chemotherapy, radiation therapy, or immunotherapy
• Patients with acute promyelocytic leukemia
• Patients with active central nervous system leukemia
• Prior treatment with Erwinaze
• Hyperleukocytosis with \> 50,000 blasts/μL
• History of a major thrombotic event
• History of pancreatitis
• Active, uncontrolled infection
• Uncontrolled intercurrent illness
• Pregnant women
• Uncontrolled active seizure disorder or a history of seizure

Sponsors & Collaborators

• Ashkan Emadi: lead

Study Sites (1)

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Asparaginase; asparaginase erwinia chrysanthemi recombinant

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Ashkan Emadi, MD, PhD

  University of Maryland

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: October 17, 2014
• First Posted: November 5, 2014
• Study Start: April 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: September 1, 2017
• Last Updated: March 12, 2018

Record last verified: 2018-02

Locations

US (1)