LeukemiaPhase 1/2NCT01126814
A Study of Imatinib With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive (AML) Acute Myeloid Leukemia
A Phase 1/2 study testing Imatinib (Gleevec) in people with Leukemia, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This is a Phase I-II study evaluating the toxicity and efficacy of imatinib combined with mitoxantrone, etoposide and high-dose cytarabine reinduction therapy in relapsed and refractory AML. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Leukemia
- What is being tested?
- Imatinib (Gleevec)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteCanada
- Study dates
- Jul 2004to Apr 2010
- Phase
- Phase 1/2
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- AML, all subtypes except APL.
- Prior induction therapy consisting of cytarabine 100-200 mg/m2 plus an anthracycline.
- One of the following:
- persistent leukemia after induction therapy.
- relapse within two years of achieving complete remission with induction therapy. Any consolidation therapy is acceptable, including stem cell transplantation.
- At least 10% bone marrow blasts, or biopsy confirmed extramedullary disease.
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- Positivity for c-kit (CD117) in at least 30% of blasts as measured by flow cytometry.
- Aged 18-65.
- ECOG performance status < 3 (see Appendix I).
- No chemotherapy within the previous four weeks, other than hydroxyurea to control counts. If hydroxyurea is used, it must be stopped at least 24 hours prior to starting imatinib.
- Able to given informed consent.
Who cannot join
- Active uncontrolled infection.
- Active CNS leukemia.
- Serum creatinine > 200 umol/L.
- Serum bilirubin > 1.5 x ULN, AST or ALT > 2x ULN.
- Left ventricular ejection fraction < 50%.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I-II Study Evaluating the Safety and Efficacy of Imatinib Mesylate (Gleevec) Combined With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive Acute Myeloid Leukemia
This is a Phase I-II study evaluating the toxicity and efficacy of imatinib combined with mitoxantrone, etoposide and high-dose cytarabine reinduction therapy in relapsed and refractory AML. Patients will be treated initially at a 200 mg dose of imatinib; if tolerated, the imatinib dose will be escalated in subsequent cohorts to 300 mg and 400 mg. Once the recommended dose is determined, the remaining patients will be treated at that dose, to evaluate the antileukemic activity of the regimen. Patients achieving complete remission will receive consolidation therapy with imatinib combined with high-dose cytarabine and mitoxantrone, followed by maintenance imatinib.
Read the detailed description
Induction therapy:
- Imatinib 200-400 mg p.o. daily x 10 days, Days 1-10 (see dose escalation scheme in Section 5.4 below).
- Mitoxantrone 10 mg/m2 daily x 5 days, Days 4-8.
- Etoposide 100 mg/m2 daily x 5 days, Days 4-8.
- Cytarabine 1.5 grams/m2 q12h x 4 doses, Days 9-10 (for patients aged 60 years and over, 1.0 gram/m2).
Only one induction course will be permitted. Only patients achieving CR will proceed to consolidation and maintenance.
Consolidation therapy, maximum 2 cycles (for patients achieving CR):
- Imatinib 200-400 mg p.o. daily x 8 days, Days 1-8 (see dose escalation scheme in Section 5.4 below).
- Mitoxantrone 12 mg/m2 daily x 2 days, Days 4-5.
- Cytarabine 3 grams/m2 q12h x 6 doses, Days 4,6,8. For patients aged 60 years and over, the dose will be reduced to 1.5 grams/m2.
Maintenance therapy (for patients still in CR at end of consolidation):
Imatinib 600 mg p.o. daily, until relapse or toxicity (see dose modification criteria in Section 5.6.6 below). Patients must receive at least one consolidation cycle before being permitted to proceed to maintenance therapy (see Section 5.6 for details). Maintenance therapy with imatinib will be provided for a maximum period of 1 year.
Dose escalation scheme:
Imatinib will be used during induction and consolidation at one of the following dose levels:
Level -1 100 mg daily Level 1 200 mg daily Level 2 300 mg daily Level 3 400 mg daily
- Conditions
- Leukemia
- Being tested
- Imatinib (Gleevec)
- Keywords
- Gleevec, c-kit, aml
- Medical subject headings
- Leukemia, Piebaldism, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib (Gleevec)Drug
| Study group | Role | What they receive |
|---|---|---|
| one | Experimental | Not described Receives: Drug: Imatinib (Gleevec) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity (hematologic and non-hematologic) of the combination of Imatinib and Chemotherapy consisting of Mitoxantrone, Etoposide and Ara-c
Hematologic toxicity
- Number of days to ANC > 0.5 and 1.0.
- Number of days until platelets > 20 and > 50, independent of platelet transfusions.
- Number of days until RBC transfusion independent. Non-hematologic toxicity, as per NCI common toxicity criteria Hematologic dose-limiting toxicity (DLT) defined as > 40 days to ANC > 0.5 or platelets > 20 independent of transfusions.
Measured: 2 years
Response rate - CR, MLFS and PR as per section 7.1
- Complete response
- Morphologic leukemia-free state
- Partial remission (PR•No response (NR): Does not meet the criteria for CR, MLFS or PR.
Measured: 2 years
Maximum tolerated dose of Imatinib when given in combination with chemotherapy
Maximum tolerated dose (MTD) of Imatinib (200, 300, 400 mg) when used in combination with NOVE-HiDAC induction and consolidation. MTD defined as highest dose resulting in up to 2/6 grade III-IV hematologic (as defined above) or non-hematologic DLTs per dose level. Non-hematologic DLTs as defined by NCIC CTC.
Measured: 2 years
Secondary outcomes (5)
Toxicity of imatinib maintenance therapy.
Hematologic
- Number of days to ANC > 0.5 and 1.0.
- Number of days until platelets > 20 and > 50, independent of platelet transfusions.
- Number of days until RBC transfusion independent. Non-hematologic toxicity, as per NCI common toxicity criteria
Measured: 2 years
Number of Participants with adverse events as a measure of safety and tolerability
Toxicity of imatinib maintenance therapy.
Measured: 2 years
Remission-free survival and overall survival.
Median duration of remission free survival. Median overall survival and 2 year overall survival.
Measured: 2 years
Total and phosphorylated c-kit activity at Days 1 and 4.
levels of total and phosphorylated c-kit - pre and post imatinib/Gleevec
Measured: 2 years
Levels of downstream components of c-kit pathway at Days 1 & 4.
levels of phosphorylation ERK and AKT - pre and post imatinib/Gleevec
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2010 (estimated)
- Study startJul 2004
- Primary completionSep 2009
- Study completionApr 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01126814
- Sponsor's protocol ID
- 04-0147-C
- Status last verified
- Jun 2015
- First submitted
- 3 May 2010
- Last updated
- 24 Jun 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I-II Study Evaluating the Safety and Efficacy of Imatinib Mesylate (Gleevec) Combined With Reinduction Chemotherapy Using Mitoxantrone, Etoposide and Cytarabine in Patients With Relapsed/Refractory C-kit Positive Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT01126814
- Acronym / sponsor ID
- 04-0147-C
- Conditions
- Leukemia
- Keywords
- Gleevec, c-kit, aml
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jul 2004
- Primary completion
- Sep 2009 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 20 May 2010 (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.
This is a Phase I-II study evaluating the toxicity and efficacy of imatinib combined with mitoxantrone, etoposide and high-dose cytarabine reinduction therapy in relapsed and refractory AML. Patients will be treated initially at a 200 mg dose of imatinib; if tolerated, the imatinib dose will be escalated in subsequent cohorts to 300 mg and 400 mg. Once the recommended dose is determined, the remaining patients will be treated at that dose, to evaluate the antileukemic activity of the regimen. Patients achieving complete remission will receive consolidation therapy with imatinib combined with high-dose cytarabine and mitoxantrone, followed by maintenance imatinib.
Detailed description
Induction therapy:
- Imatinib 200-400 mg p.o. daily x 10 days, Days 1-10 (see dose escalation scheme in Section 5.4 below).
- Mitoxantrone 10 mg/m2 daily x 5 days, Days 4-8.
- Etoposide 100 mg/m2 daily x 5 days, Days 4-8.
- Cytarabine 1.5 grams/m2 q12h x 4 doses, Days 9-10 (for patients aged 60 years and over, 1.0 gram/m2).
Only one induction course will be permitted. Only patients achieving CR will proceed to consolidation and maintenance.
Consolidation therapy, maximum 2 cycles (for patients achieving CR):
- Imatinib 200-400 mg p.o. daily x 8 days, Days 1-8 (see dose escalation scheme in Section 5.4 below).
- Mitoxantrone 12 mg/m2 daily x 2 days, Days 4-5.
- Cytarabine 3 grams/m2 q12h x 6 doses, Days 4,6,8. For patients aged 60 years and over, the dose will be reduced to 1.5 grams/m2.
Maintenance therapy (for patients still in CR at end of consolidation):
Imatinib 600 mg p.o. daily, until relapse or toxicity (see dose modification criteria in Section 5.6.6 below). Patients must receive at least one consolidation cycle before being permitted to proceed to maintenance therapy (see Section 5.6 for details). Maintenance therapy with imatinib will be provided for a maximum period of 1 year.
Dose escalation scheme:
Imatinib will be used during induction and consolidation at one of the following dose levels:
Level -1 100 mg daily Level 1 200 mg daily Level 2 300 mg daily Level 3 400 mg daily
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| one | Experimental | Drug: Imatinib (Gleevec) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- AML, all subtypes except APL.
- Prior induction therapy consisting of cytarabine 100-200 mg/m2 plus an anthracycline.
- One of the following:
- At least 10% bone marrow blasts, or biopsy confirmed extramedullary disease.
- Positivity for c-kit (CD117) in at least 30% of blasts as measured by flow cytometry.
Key exclusion criteria (5 listed)
- Active uncontrolled infection.
- Active CNS leukemia.
- Serum creatinine > 200 umol/L.
- Serum bilirubin > 1.5 x ULN, AST or ALT > 2x ULN.
- Left ventricular ejection fraction < 50%.
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 |
|---|---|---|
| Imatinib (Gleevec) | Drug | one |
Primary outcome
Toxicity (hematologic and non-hematologic) of the combination of Imatinib and Chemotherapy consisting of Mitoxantrone, Etoposide and Ara-c
Time frame: 2 years
Hematologic toxicity * Number of days to ANC > 0.5 and 1.0. * Number of days until platelets > 20 and > 50, independent of platelet transfusions. * Number of days until RBC transfusion independent. Non-hematologic toxicity, as per NCI common toxicity criteria Hematologic dose-limiting toxicity (DLT) defined as > 40 days to ANC > 0.5 or platelets > 20 independent of transfusions.
Response rate - CR, MLFS and PR as per section 7.1
Time frame: 2 years
* Complete response * Morphologic leukemia-free state * Partial remission (PR•No response (NR): Does not meet the criteria for CR, MLFS or PR.
Maximum tolerated dose of Imatinib when given in combination with chemotherapy
Time frame: 2 years
Maximum tolerated dose (MTD) of Imatinib (200, 300, 400 mg) when used in combination with NOVE-HiDAC induction and consolidation. MTD defined as highest dose resulting in up to 2/6 grade III-IV hematologic (as defined above) or non-hematologic DLTs per dose level. Non-hematologic DLTs as defined by NCIC CTC.
5 secondary outcomes
Toxicity of imatinib maintenance therapy.
Time frame: 2 years
Number of Participants with adverse events as a measure of safety and tolerability
Time frame: 2 years
Remission-free survival and overall survival.
Time frame: 2 years
Total and phosphorylated c-kit activity at Days 1 and 4.
Time frame: 2 years
Levels of downstream components of c-kit pathway at Days 1 & 4.
Time frame: 2 years
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 24 Jun 2015.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Imatinib (Gleevec) in people with Leukemia, run by University Health Network, Toronto at 1 site in Canada.
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 5 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 24 Jun 2015. 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 Canada. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Toxicity (hematologic and non-hematologic) of the combination of Imatinib and Chemotherapy consisting of Mitoxantrone, Etoposide and Ara-c (time frame: 2 years). 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?
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 24 Jun 2015.