Acute Myeloid LeukemiaPhase 1NCT02283190
1336GCC: Study of Erwinaze for Treatment of Acute Myeloid Leukemia (AML)
A Phase 1 study testing Erwinase in people with Acute Myeloid Leukemia, run by Ashkan Emadi at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia
- What is being tested?
- Erwinase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2014to Sep 2017
- 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
- Histologically or cytologically confirmed AML
- 18 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
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- 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.
Who cannot join
- 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
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- History of pancreatitis
- Active, uncontrolled infection
- Uncontrolled intercurrent illness
- Pregnant women
- Uncontrolled active seizure disorder or a history of seizure
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
About this study
Official title: 1336GCC: Open-Label, Single-Arm PK Study of IV Erwinaze (Asparaginase Erwinia Chrysanthemi) to Find the Dose With Acceptable Therapeutic and Safety Profile in Adults With Acute Myeloid Leukemia With or Without Isocitrate Dehydrogenase Mutations
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.
Read the detailed description
For safety:
Erwinaze has been already used in clinical practice for treatment of patients with acute leukemia with known side effect profile. For this reason, in this protocol, we use the "3+3+3" design for evaluation of safety based on pre-determined dose-limiting toxicities (DLT). In the "3+3+3" design, the dose escalation rules proceed by adjusting the dose in cohorts of 3 to 9 patients per three dose levels:20,000 IU/m2 (dose cohort -1), 25,000 IU/m2 (dose cohort 0), 30,000 IU/m2 (dose cohort +1). The goal is to determine the Recommended Phase 2 Dose (RP2D)
For anti-leukemic activity:
To evaluate the activity of Erwinaze to reduce the serum glutamine to the desired level, the dose will be adjusted according to a pre-defined algorithm based on 48-hour trough serum glutamine level (biochemical response) prior to dose 6 of each patient. If the safety profile is acceptable, we will enroll up to a total of 15 patients at that dose level to better study and analyze the glutamine-reducing effect of Erwinaze at the defined dose.
In summary, if 9 patients are treated at a certain dose and at least 7 out of 9 individuals respond to treatment (per serum glutamine levels) and < 3 develop DLT, this dose level will be declared the Recommended Phase 2 Dose (RP2D). Six additional patients (total of 15 to 18 patients) will be enrolled at the RP2D level to better assess toxicity and to document responses.
There will be no intra-patient dose escalation or reduction.
- Conditions
- Acute Myeloid Leukemia
- Being tested
- Erwinase
- Keywords
- Asparaginase, Glutamine
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErwinaseDrug
Also called Asparaginase, Crisantaspase
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Erwinase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 42
Secondary outcomes (4)
Efficacy of Erwinase doses as measured by nadir serum asparaginase activity
The dose of Erwinase that produces nadir serum asparaginase activity ≥0.1 IU/mL with acceptable safety profile.
Measured: Days 3, 5,8,10,12, & 42
Efficacy of Erwinase as measured by acute myeloid leukemia (AML) disease response
Bone marrow biopsy to determine the clinical response to 6 doses of Erwinaze at the administered dose.
Measured: Days 15 and 29
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
To establish safety and tolerability of Erwinaze in patients with AML with or without mIDH
Measured: 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
Measure the blood and urine 2-hydroxyglutarate (2-HG) levels
Measured: Days 0, 8, & 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2014 (estimated)
- Study startApr 2014
- Primary completionDec 2015
- Study completionSep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ashkan Emadi
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ashkan Emadi, University of Maryland
- Investigators
- Ashkan Emadi, MD, PhD, Principal investigator, University of Maryland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02283190
- Sponsor's protocol ID
- 1336GCC, HP-00056335
- Status last verified
- Feb 2018
- First submitted
- 17 Oct 2014
- Last updated
- 12 Mar 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 1336GCC: Open-Label, Single-Arm PK Study of IV Erwinaze (Asparaginase Erwinia Chrysanthemi) to Find the Dose With Acceptable Therapeutic and Safety Profile in Adults With Acute Myeloid Leukemia With or Without Isocitrate Dehydrogenase Mutations
- ClinicalTrials.gov ID
- NCT02283190
- Acronym / sponsor ID
- 1336GCC, HP-00056335
- Conditions
- Acute Myeloid Leukemia
- Keywords
- Asparaginase, Glutamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Ashkan EmadiUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Sep 2017 (actual)
- First posted
- 5 Nov 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
For safety:
Erwinaze has been already used in clinical practice for treatment of patients with acute leukemia with known side effect profile. For this reason, in this protocol, we use the "3+3+3" design for evaluation of safety based on pre-determined dose-limiting toxicities (DLT). In the "3+3+3" design, the dose escalation rules proceed by adjusting the dose in cohorts of 3 to 9 patients per three dose levels:20,000 IU/m2 (dose cohort -1), 25,000 IU/m2 (dose cohort 0), 30,000 IU/m2 (dose cohort +1). The goal is to determine the Recommended Phase 2 Dose (RP2D)
For anti-leukemic activity:
To evaluate the activity of Erwinaze to reduce the serum glutamine to the desired level, the dose will be adjusted according to a pre-defined algorithm based on 48-hour trough serum glutamine level (biochemical response) prior to dose 6 of each patient. If the safety profile is acceptable, we will enroll up to a total of 15 patients at that dose level to better study and analyze the glutamine-reducing effect of Erwinaze at the defined dose.
In summary, if 9 patients are treated at a certain dose and at least 7 out of 9 individuals respond to treatment (per serum glutamine levels) and < 3 develop DLT, this dose level will be declared the Recommended Phase 2 Dose (RP2D). Six additional patients (total of 15 to 18 patients) will be enrolled at the RP2D level to better assess toxicity and to document responses.
There will be no intra-patient dose escalation or reduction.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ewwinase | Experimental | Drug: ErwinaseSix 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologically or cytologically confirmed AML
- 18 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErwinaseAlso: Asparaginase, CrisantaspaseSix 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. | Drug | Ewwinase |
Primary outcome
To determine the dose of Erwinase that produces a plasma glutamine level ≤120 μmol/L with an acceptable safety profile.
Time frame: Day 3
The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.
Efficacy of Erwinase doses as measured by plasma glutamine level
Time frame: Day 5
The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.
Efficacy of Erwinase doses as measured by plasma glutamine level
Time frame: Day 8
The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.
Efficacy of Erwinase doses as measured by plasma glutamine level
Time frame: Day 10
The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.
Efficacy of Erwinase doses as measured by plasma glutamine level
Time frame: Day 12
The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.
Efficacy of Erwinase doses as measured by plasma glutamine level
Time frame: Day 42
The dose of Erwinase that produces a plasma glutamine level ≤120 µmol/L with an acceptable safety profile.
4 secondary outcomes
Efficacy of Erwinase doses as measured by nadir serum asparaginase activity
Time frame: Days 3, 5,8,10,12, & 42
Efficacy of Erwinase as measured by acute myeloid leukemia (AML) disease response
Time frame: Days 15 and 29
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 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
Time frame: Days 0, 8, & 42
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashkan Emadi, MD, PhD principal investigator
University of Maryland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Erwinase in people with Acute Myeloid Leukemia, run by Ashkan Emadi at 1 site 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 13 inclusion and 11 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 12 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
To determine the dose of Erwinase that produces a plasma glutamine level ≤120 μmol/L with an acceptable safety profile. (time frame: Day 3). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 12 Mar 2018.