Relapsed Acute Lymphoblastic LeukemiaPhase 1NCT00928200
Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (IND 104224)
A Phase 1 study testing Erwinase, Vincristine and Dexamethasone in people with Relapsed Acute Lymphoblastic Leukemia and Allergy to PEG e.Coli Asparaginase, run by Therapeutic Advances in Childhood Leukemia Consortium at 1 site in United States.
Trial summary
This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Relapsed Acute Lymphoblastic Leukemia, Allergy to PEG e.Coli Asparaginase, Allergy to Native e.Coli Asparaginase
- What is being tested?
- Erwinase, Vincristine and Dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Apr 2009to 4 Jun 2010
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- Prior Stroke Patients with a prior history of asparaginase associated stroke are excluded. Patients with a history of other asparaginase related deep-venous thromboses (including intra-cranial thromboses without evidence of stroke or hemorrhage) are eligible.
- Down Syndrome Patients with Down Syndrome will be excluded.
- Prior Pancreatitis Patients with prior history of Grade 2 or greater asparaginase-induced symptomatic pancreatitis will be excluded.
- Renal Function Patients will be excluded if their serum creatinine is > 1.5 x the upper limit of normal for age at the institution's laboratory.
- Liver/Pancreatic Function
- Patients will be excluded if their lab results are as follows:
Show all 15Show fewer
- Direct bilirubin > 1.5x the institutional ULN for age. A total bilirubin result that is less than 1.5 times the institutional ULN for age may be used for eligibility if a direct bilirubin result is not available.
- SGPT (ALT) > 4 x institutional ULN
- Amylase or Lipase > 2 x institutional ULN
- Cardiac Function Patients will be excluded if their shortening fraction by echocardiogram is less than the institutional normal for age or an ejection fraction by MUGA is less than the institutional normal for age.
- Infection Patients will be excluded if they have an active uncontrolled infection.
- Patients planning on receiving other investigational agents while on this study. (An investigational agent is defined as any drug not currently approved for use in humans.)
- Patients planning on receiving other anti-cancer therapies while on this study.
- Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
- Patients who have started protocol therapy prior to enrollment. Patient may still enroll if IT therapy was given within 72 hours of study enrollment as part of the diagnostic lumbar procedure.
Trial locations and contacts
1 site in 1 country.
United States1 site
Childrens Hospital Los Angeles
Los Angeles, California, 90027
About this study
Official title: Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)
This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. This study will administer the drug intravenously instead of the usual intramuscular route. The dose of Erwinia will be escalated in the absence of dose limiting toxicity. Patients must have first or second relapse ALL with a history of prior systemic reaction to E. coli asparaginase.
Read the detailed description
Significance
- Substitution of Erwinase after E.coli asparaginase allergy has been standard practice despite the paucity of evidence regarding its efficacy and uncertainty about dose. Definition of an appropriate dose and schedule of Erwinase that provides reliable asparagine depletion may be useful for patients with clinical allergy to E. coli asparaginase, both in first remission or after relapse.
- Patients in relapse may have a different level of asparagine synthesis than patients maintaining remission and require different asparaginase dosing.5
- Intravenous administration provides more rapid and predictable asparagine depletion with less discomfort and danger of bleeding for often thrombocytopenic patients than intramuscular administration.
- Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with first marrow relapse.
- Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with second marrow relapse, if the duration of CR2 > 18 months year.
- Conditions
- Relapsed Acute Lymphoblastic Leukemia, Allergy to PEG e.Coli Asparaginase, Allergy to Native e.Coli Asparaginase
- Being tested
- Erwinase, Vincristine, Dexamethasone, Doxorubicin, Cytarabine
- Keywords
- Relapsed, Allergy, Erwinia, Acute, Lymphoblastic, Leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Recurrence, Hypersensitivity, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErwinaseDrug
Also called Asparaginase, Elspar, Kidrolase, L-Asparaginase
The dose of Erwinase will be assigned at study entry. The first dose of Erwinase wil be given between Days 3-5 and will continue on a M-W-F schedule for a total of 10 doses.
Erwinase will be administered as a 2-hour intravenous infusion.
VincristineDrug
Also called Oncovin, Vincasar Pfs, Vincristine Sulfate, LCR
1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22
DexamethasoneDrug
Also called Decadron, Dexasone, Diodex, Hexadrol
10 mg/m2/day divided BID. Give by mouth days 1-14.
DoxorubicinDrug
Also called Adriamycin, Rubex
60 mg/m2/day IV over 15 minutes on day 1
CytarabineDrug
Also called Cytosar-U, Ara-C, Arabinosylcytosine
Given Intrathecally at the dose defined by age on day 1. 30 mg for age 1-1.99 50 mg for age 2-2.99 70 mg for age 3 and older
MethotrexateDrug
Also called Otrexup, Rasuvo, Rheumatrex, Trexall
Given Intrathecally to all patients who are CNS 1 or 2 at study entry. Dose defined by age. Given on day 15 8mg for age 1-1.99 10 mg for age 2-2.99 12 mg for age 3-8.99 15 mg for age 9 and older
Triple Intrathecal TherapyDrug
Methotrexate, Cytarabine and Hydrocortisone given Intrathecally on day 8, 15 and 22 for patients who are CNS 3 at study entry. Doses determined by age.
DexrazoxaneDrug
Also called Zinecard
Due to the limited availability of Dexrazoxane (Zinecard®), treatment will be at the discretion of the treating physician. Dose should be 600 mg/m2 as a IV push immediately prior to anthracycline dose (the elapsed time from the beginning of the dexrazoxane dose to the end of the anthracycline infusion should be 30 minutes or less).
| Study group | Role | What they receive |
|---|---|---|
| Single Arm | Experimental | All patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22. Receives: Drug: Erwinase; Drug: Vincristine; Drug: Dexamethasone; Drug: Doxorubicin; Drug: Cytarabine; Drug: Methotrexate; Drug: Triple Intrathecal Therapy; Drug: Dexrazoxane |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of a Dose-Limiting Toxicity
The MTD in each stratum will be the highest dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy.
Measured: Beginning with the first dose of investigational product until 30 days following the last dose of Erwinase
Secondary outcomes (2)
Response Rate and Minimum Residual Disease
Disease response evaluated by examination and labs. MRD evaluated from marrow samples.
Measured: After completion of treatment course
Asparaginase Activity
Activity levels assessed from PK sampling
Measured: PK samples to be collected Pre-Tx, and and Erwinase Doses 3, 6 and 9 and Day 29
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2009 (estimated)
- Study start13 Apr 2009
- Primary completion4 Jun 2010
- Study completion4 Jun 2010
Why it stopped: Study was terminated due to lack of accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Relapsed Acute Lymphoblastic 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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Therapeutic Advances in Childhood Leukemia Consortium
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Heather Grossman, MD, Study chair, Children's Hopital New YorkPaul Gaynon, MD, Principal investigator, Children's Hospital Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00928200
- Sponsor's protocol ID
- T2006-002
- Status last verified
- Jul 2018
- First submitted
- 24 Jun 2009
- Last updated
- 19 Feb 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intravenous Erwinase for Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia and Allergy to E. Coli Asparaginase (IND 104224)
- ClinicalTrials.gov ID
- NCT00928200
- Acronym / sponsor ID
- T2006-002
- Conditions
- Relapsed Acute Lymphoblastic Leukemia, Allergy to PEG e.Coli Asparaginase, Allergy to Native e.Coli Asparaginase
- Keywords
- Relapsed, Allergy, Erwinia, Acute, Lymphoblastic, Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was terminated due to lack of accrual.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Therapeutic Advances in Childhood Leukemia ConsortiumUniversity, hospital or other
- Study start
- 13 Apr 2009
- Primary completion
- 4 Jun 2010 (actual)
- Study completion
- 4 Jun 2010 (actual)
- First posted
- 25 Jun 2009 (estimated)
- Results
- Posted 19 Feb 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase I study using the Erwinia form of asparaginase in place of the E. coli form using a standard re-induction regimen (Vincristine, Dexamethasone, Doxorubicin) for patients with relapsed ALL who have developed an allergy to the E. coli formulation. This study will administer the drug intravenously instead of the usual intramuscular route. The dose of Erwinia will be escalated in the absence of dose limiting toxicity. Patients must have first or second relapse ALL with a history of prior systemic reaction to E. coli asparaginase.
Detailed description
Significance
- Substitution of Erwinase after E.coli asparaginase allergy has been standard practice despite the paucity of evidence regarding its efficacy and uncertainty about dose. Definition of an appropriate dose and schedule of Erwinase that provides reliable asparagine depletion may be useful for patients with clinical allergy to E. coli asparaginase, both in first remission or after relapse.
- Patients in relapse may have a different level of asparagine synthesis than patients maintaining remission and require different asparaginase dosing.5
- Intravenous administration provides more rapid and predictable asparagine depletion with less discomfort and danger of bleeding for often thrombocytopenic patients than intramuscular administration.
- Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with first marrow relapse.
- Vincristine, doxorubicin, asparaginase, and dexamethasone with dexrazoxane is clinically relevant for a population with second marrow relapse, if the duration of CR2 > 18 months year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm | Experimental | Drug: Erwinase, Drug: Vincristine, Drug: Dexamethasone, Drug: Doxorubicin, Drug: Cytarabine, Drug: Methotrexate, Drug: Triple Intrathecal Therapy, Drug: DexrazoxaneAll patients receive Vincristine, Dexamethasone, Doxorubicin, and Cytarabine. Dexrazoxane optional on Day 1. Erwinase is started between Days 3-5 and is given every M-W-F for a total of 10 doses. Patients with CNS 1 or 2 receive Methotrexate intrathecally on Day 15. Patients with CNS 3 receive Triple Intrathecal Therapy (Methotrexate, Cytarabine and Hydrocortisone) on Days 8, 15, and 22. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (15 listed)
- Prior Stroke Patients with a prior history of asparaginase associated stroke are excluded. Patients with a history of other asparaginase related deep-venous thromboses (including intra-cranial thromboses without evidence of stroke or hemorrhage) are eligible.
- Down Syndrome Patients with Down Syndrome will be excluded.
- Prior Pancreatitis Patients with prior history of Grade 2 or greater asparaginase-induced symptomatic pancreatitis will be excluded.
- Renal Function Patients will be excluded if their serum creatinine is > 1.5 x the upper limit of normal for age at the institution's laboratory.
- Liver/Pancreatic Function
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, Elspar, Kidrolase, L-AsparaginaseThe dose of Erwinase will be assigned at study entry. The first dose of Erwinase wil be given between Days 3-5 and will continue on a M-W-F schedule for a total of 10 doses. Erwinase will be administered as a 2-hour intravenous infusion. | Drug | Single Arm |
| VincristineAlso: Oncovin, Vincasar Pfs, Vincristine Sulfate, LCR1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22 | Drug | Single Arm |
| DexamethasoneAlso: Decadron, Dexasone, Diodex, Hexadrol10 mg/m2/day divided BID. Give by mouth days 1-14. | Drug | Single Arm |
| DoxorubicinAlso: Adriamycin, Rubex60 mg/m2/day IV over 15 minutes on day 1 | Drug | Single Arm |
| CytarabineAlso: Cytosar-U, Ara-C, ArabinosylcytosineGiven Intrathecally at the dose defined by age on day 1. 30 mg for age 1-1.99 50 mg for age 2-2.99 70 mg for age 3 and older | Drug | Single Arm |
| MethotrexateAlso: Otrexup, Rasuvo, Rheumatrex, TrexallGiven Intrathecally to all patients who are CNS 1 or 2 at study entry. Dose defined by age. Given on day 15 8mg for age 1-1.99 10 mg for age 2-2.99 12 mg for age 3-8.99 15 mg for age 9 and older | Drug | Single Arm |
| Triple Intrathecal TherapyMethotrexate, Cytarabine and Hydrocortisone given Intrathecally on day 8, 15 and 22 for patients who are CNS 3 at study entry. Doses determined by age. | Drug | Single Arm |
| DexrazoxaneAlso: ZinecardDue to the limited availability of Dexrazoxane (Zinecard®), treatment will be at the discretion of the treating physician. Dose should be 600 mg/m2 as a IV push immediately prior to anthracycline dose (the elapsed time from the beginning of the dexrazoxane dose to the end of the anthracycline infusion should be 30 minutes or less). | Drug | Single Arm |
Primary outcome
Occurrence of a Dose-Limiting Toxicity
Time frame: Beginning with the first dose of investigational product until 30 days following the last dose of Erwinase
The MTD in each stratum will be the highest dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy.
2 secondary outcomes
Response Rate and Minimum Residual Disease
Time frame: After completion of treatment course
Asparaginase Activity
Time frame: PK samples to be collected Pre-Tx, and and Erwinase Doses 3, 6 and 9 and Day 29
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Therapeutic Advances in Childhood Leukemia \& Lymphoma Consortium web siteLink provided by the sponsor.
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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.
Heather Grossman, MD study chair
Children's Hopital New York
Paul Gaynon, MD principal investigator
Children's Hospital Los Angeles
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, Vincristine and Dexamethasone in people with Relapsed Acute Lymphoblastic Leukemia and Allergy to PEG e.Coli Asparaginase, run by Therapeutic Advances in Childhood Leukemia Consortium 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 0 inclusion and 15 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: stopped early, as of the sponsor's last update on 19 Feb 2019. 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?
Yes. Results are posted in the registry (first posted 19 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Occurrence of a Dose-Limiting Toxicity (time frame: Beginning with the first dose of investigational product until 30 days following the last dose of Erwinase). 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 19 Feb 2019.