LeukemiaPhase 2NCT00509093
Imatinib Mesylate in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Who Have Received Chemotherapy
A Phase 2 study testing imatinib mesylate, gene expression analysis and mutation analysis in people with Leukemia, run by Case Comprehensive Cancer Center at 4 sites in United States.
Trial summary
RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with newly diagnosed acute myeloid leukemia who have received chemotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- imatinib mesylate, gene expression analysis and mutation analysis
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 4 sitesUnited States
- Study dates
- Oct 2008to 9 Apr 2015
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnostic bone marrow aspirate/ biopsy or peripheral blood confirming AML.
- At the time of diagnosis, patients must have c-kit (also known as CD117) positive AML (20% or more of the blasts express c-kit[CD117]).
- A flow scattergram (from the diagnostic AML specimen) must be available to calculate a c-kit MFI.
- Patients must have received standard induction chemotherapy with ADE (cytarabine, daunorubicin, and etoposide) or with 7+3 (7 days of cytarabine continuous infusion and 3 days of an anthracycline (idarubicin, daunorubicin, or mitoxantrone). Patients with persistent leukemia on a Day 10-28 marrow may have received a second course of chemotherapy.
- After the completion of induction therapy, patients must have attained a complete remission based on blood count recovery (neutrophil count ≥ 1,000/µL, platelet count ≥ 100,000/µL), and bone marrow aspirate and biopsy (< 5% myeloblasts).
- For patients < 60 years of age, patients must have received at least 2 courses of post-remission therapy with at least intermediate dose (400 mg/m2/day). *Patients with t(8;21) or inversion 16 at the time of diagnosis must have received at least 2 courses of high dose cytarabine. For patients > or = 60 years of age, patients must have received 1 course of post-remission therapy (the type of chemotherapy will not be specified).
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- Patients must be registered on this study (maintenance Imatinib mesylate) within 60 days of the last dose of post-remission therapy.
- A bone marrow aspirate and/or biopsy must be done within 3 weeks of registration documenting CR.
- Women of childbearing potential and sexually active males must use an effective method of contraception.
- Female patients of childbearing potential must have negative pregnancy test within 7 days before initiation of study drug dosing. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. Male and female patients of reproductive potential must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug.
- ECOG Performance Status 0-2.
- Creatinine must be ≤ 1.5 x upper limit of normal.
- Total bilirubin must be ≤ 2 mg/dl and AST and ALT must be ≤ 2 times the upper limit of normal.
- Previous treatment-related toxicities must have resolved to ≤ Grade 1 excluding alopecia.
- Written, voluntary informed consent.
Who cannot join
- Acute promyelocytic leukemia.
- Patients with an autologous or allogeneic bone marrow transplant.
- History of HIV.
- Pregnant or breast-feeding.
- Serious or poorly controlled medical conditions that would interfere with the protocol.
- At the time of study entry, any medications which could significantly interact with imatinib mesylate must be discontinued.
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- Patients with active extramedullary disease are not eligible.
- Patient has received any other investigational agents within 28 days of first day of study drug dosing.
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ. Existence of any other malignant disease is not allowed.
- Patient with Grade III/IV cardiac problems as defined by the New York Heart Association Criteria. (i.e., congestive heart failure, myocardial infarction within 6 months of study)
- Patient has known chronic liver disease (i.e., chronic active hepatitis, and cirrhosis).
- Patient previously received radiotherapy to ≥ 25 % of the bone marrow
- Patient had a major surgery within 2 weeks prior to study entry.
- Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Roswell Park Cancer Institute
Buffalo, New York, 14263
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: A Phase 2 Study of Imatinib Mesylate (Gleevec) as Maintenance Therapy After Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed C-kit Positive Acute Myeloid Leukemia
RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with newly diagnosed acute myeloid leukemia who have received chemotherapy.
Read the detailed description
OBJECTIVES:
Primary
- To determine whether adding imatinib mesylate as maintenance therapy improves progression-free survival in patients with c-kit positive acute myeloid leukemia (AML) compared with historical controls.
Secondary
- To assess the feasibility of administering imatinib mesylate as maintenance therapy after the completion of induction and consolidation therapy in these patients.
- To evaluate potential mechanisms of relapse/resistance in c-kit positive AML by examining multidrug resistance gene expression and AF1q gene expression and to determine whether these levels correlate with c-kit expression.
OUTLINE: This is a multicenter study.
Patients receive oral imatinib mesylate once daily for up to 12 months.
Bone marrow and peripheral blood are collected at baseline. Laboratory endpoints are evaluated by flow cytometry; mutation and gene analysis by PCR.
- Conditions
- Leukemia
- Being tested
- imatinib mesylate, gene expression analysis, mutation analysis, polymerase chain reaction, flow cytometry
- Keywords
- adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myelomonocytic leukemia (M4), adult acute megakaryoblastic leukemia (M7), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult acute myeloid leukemia in remission
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Congenital Abnormalities, Leukemia, Myelomonocytic, Acute, Leukemia, Megakaryoblastic, Acute, Leukemia, Monocytic, Acute, Leukemia, Erythroblastic, Acute, Leukemia, Basophilic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
imatinib mesylateDrug
Also called Gleevec
Patients will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. The study dose can be split but the dose of 600 mg must be given within a 12 hour period.
gene expression analysisGenetic
Also called MRD
Multidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed.
mutation analysisGenetic
Also called FLT3
FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR.
polymerase chain reactionGenetic
Also called AF1Q gene analysis
AF1q gene analysis (on bone marrow aspirate)
flow cytometryOther
Also called C-kit MFI, CD117
C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated as the c-kit mean channel number (MCN) of the blasts/ MCN auto fluorescence.
biopsyProcedure or surgery
Also called bone marrow biopsy/aspirate
Diagnostic bone marrow biopsy/aspirate must be done within 3 weeks of registration documenting complete remission
| Study group | Role | What they receive |
|---|---|---|
| Imatinib Mesylate | Experimental | Not described Receives: Drug: imatinib mesylate; Genetic: gene expression analysis; Genetic: mutation analysis; Genetic: polymerase chain reaction; Other: flow cytometry; Procedure: biopsy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Median Progression-free Survival (PFS) for Patients Less Than 60 Years of Age
PFS measured from the date of Complete Response (CR) to the date of relapse or death. Progression defined as any of the following event: progression to accelerated phase or blast crisis, death, loss of CHR or MCyR, or in patients not achieving a CHR an increasing WBC despite appropriate therapeutic management
This outcome will be reported as median progression-free survival in months for participants less than 60 years of age.
Measured: up to 5 years from the End of Treatment
Progression-free Survival for Patients 60 Years of Age and Older
Progression free survival will be measured from the date of Complete Response (CR) to the date of relapse or death.
Measured: up to 5 years from the End of Treatment
Percent of Participants Less Than 60 Years of Age With PFS at 8 and 13 Months Post-treatment
Percent of participants less than 60 years of age with PFS at 8 and 13 months post-treatment
Measured: at 8 and 13 months after treatment.
Percent of Participants 60 Years of Age or Older With PFS at 8 and 13 Months Post-treatment
Percent of participants 60 years of age or older with PFS at 8 and 13 months post-treatment
Measured: at 8 and 13 months after treatment.
Secondary outcomes (1)
Toxicity as Measured by NCI CTC v. 3.0
Number of patients (%) experiencing an adverse event
See adverse events section for details
Measured: 13 months from start of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2007 (estimated)
- Study startOct 2008
- Primary completion9 May 2014
- Study completion9 Apr 2015
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Anjali Advani, MD, Principal investigator, Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer CenterBrenda Cooper, MD, Principal investigator, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00509093
- Sponsor's protocol ID
- CASE4906
- Other IDs
- P30CA043703, CASE4906, AUS259, NCI-2010-01198
- Status last verified
- Mar 2020
- First submitted
- 30 Jul 2007
- Last updated
- 17 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Study of Imatinib Mesylate (Gleevec) as Maintenance Therapy After Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed C-kit Positive Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT00509093
- Acronym / sponsor ID
- CASE4906
- Conditions
- Leukemia
- Keywords
- adult acute minimally differentiated myeloid leukemia (M0), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myelomonocytic leukemia (M4)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2008
- Primary completion
- 9 May 2014 (actual)
- Study completion
- 9 Apr 2015 (actual)
- First posted
- 31 Jul 2007 (estimated)
- Results
- Posted 4 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Imatinib mesylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase II trial is studying how well imatinib mesylate works in treating patients with newly diagnosed acute myeloid leukemia who have received chemotherapy.
Detailed description
OBJECTIVES:
Primary
- To determine whether adding imatinib mesylate as maintenance therapy improves progression-free survival in patients with c-kit positive acute myeloid leukemia (AML) compared with historical controls.
Secondary
- To assess the feasibility of administering imatinib mesylate as maintenance therapy after the completion of induction and consolidation therapy in these patients.
- To evaluate potential mechanisms of relapse/resistance in c-kit positive AML by examining multidrug resistance gene expression and AF1q gene expression and to determine whether these levels correlate with c-kit expression.
OUTLINE: This is a multicenter study.
Patients receive oral imatinib mesylate once daily for up to 12 months.
Bone marrow and peripheral blood are collected at baseline. Laboratory endpoints are evaluated by flow cytometry; mutation and gene analysis by PCR.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Imatinib Mesylate | Experimental | Drug: imatinib mesylate, Genetic: gene expression analysis, Genetic: mutation analysis, Genetic: polymerase chain reaction, Other: flow cytometry, Procedure: biopsy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Diagnostic bone marrow aspirate/ biopsy or peripheral blood confirming AML.
- At the time of diagnosis, patients must have c-kit (also known as CD117) positive AML (20% or more of the blasts express c-kit[CD117]).
- A flow scattergram (from the diagnostic AML specimen) must be available to calculate a c-kit MFI.
- Patients must have received standard induction chemotherapy with ADE (cytarabine, daunorubicin, and etoposide) or with 7+3 (7 days of cytarabine continuous infusion and 3 days of an anthracycline (idarubicin, daunorubicin, or mitoxantrone). Patients with persistent leukemia on a Day 10-28 marrow may have received a second course of chemotherapy.
- After the completion of induction therapy, patients must have attained a complete remission based on blood count recovery (neutrophil count ≥ 1,000/µL, platelet count ≥ 100,000/µL), and bone marrow aspirate and biopsy (< 5% myeloblasts).
Key exclusion criteria (14 listed)
- Acute promyelocytic leukemia.
- Patients with an autologous or allogeneic bone marrow transplant.
- History of HIV.
- Pregnant or breast-feeding.
- Serious or poorly controlled medical conditions that would interfere with the protocol.
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 mesylateAlso: GleevecPatients will receive treatment with imatinib mesylate at a dose of 600 mg by mouth once a day for 12 months. The study dose can be split but the dose of 600 mg must be given within a 12 hour period. | Drug | Imatinib Mesylate |
| gene expression analysisAlso: MRDMultidrug resistance genes: These studies will include: MDR1, MRP1, LRP, and BCRP. Bone marrow blocks or cut slides will be sent to Duke on the diagnostic AML samples. DNA will be eluted from the samples so that the above genes can be analyzed. | Genetic | Imatinib Mesylate |
| mutation analysisAlso: FLT3FLT3 mutation analysis (on bone marrow aspirate or peripheral blood): These analyses will be performed by pathology at the time of diagnosis, at the participating institution. Samples will be analyzed for the FLT3 ITD and/or D835 mutation by PCR. | Genetic | Imatinib Mesylate |
| polymerase chain reactionAlso: AF1Q gene analysisAF1q gene analysis (on bone marrow aspirate) | Genetic | Imatinib Mesylate |
| flow cytometryAlso: C-kit MFI, CD117C-kit MFI on AML samples will be calculated by using a CD45/ orthogonal light scatter gate to isolate blasts. The MFI will be calculated as the c-kit mean channel number (MCN) of the blasts/ MCN auto fluorescence. | Other | Imatinib Mesylate |
| biopsyAlso: bone marrow biopsy/aspirateDiagnostic bone marrow biopsy/aspirate must be done within 3 weeks of registration documenting complete remission | Procedure or surgery | Imatinib Mesylate |
Primary outcome
Median Progression-free Survival (PFS) for Patients Less Than 60 Years of Age
Time frame: up to 5 years from the End of Treatment
PFS measured from the date of Complete Response (CR) to the date of relapse or death. Progression defined as any of the following event: progression to accelerated phase or blast crisis, death, loss of CHR or MCyR, or in patients not achieving a CHR an increasing WBC despite appropriate therapeutic management This outcome will be reported as median progression-free survival in months for participants less than 60 years of age.
Progression-free Survival for Patients 60 Years of Age and Older
Time frame: up to 5 years from the End of Treatment
Progression free survival will be measured from the date of Complete Response (CR) to the date of relapse or death.
Percent of Participants Less Than 60 Years of Age With PFS at 8 and 13 Months Post-treatment
Time frame: at 8 and 13 months after treatment.
Percent of participants less than 60 years of age with PFS at 8 and 13 months post-treatment
Percent of Participants 60 Years of Age or Older With PFS at 8 and 13 Months Post-treatment
Time frame: at 8 and 13 months after treatment.
Percent of participants 60 years of age or older with PFS at 8 and 13 months post-treatment
1 secondary outcome
Toxicity as Measured by NCI CTC v. 3.0
Time frame: 13 months from start of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Anjali Advani, MD principal investigator
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Brenda Cooper, MD principal investigator
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing imatinib mesylate, gene expression analysis and mutation analysis in people with Leukemia, run by Case Comprehensive Cancer Center at 4 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 15 inclusion and 14 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 17 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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 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?
Yes. Results are posted in the registry (first posted 4 Mar 2020). 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?
Median Progression-free Survival (PFS) for Patients Less Than 60 Years of Age (time frame: up to 5 years from the End of Treatment). The study lists 4 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 17 Mar 2020.