Leukemia, MyeloidPhase 2NCT00611247
Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia
A Phase 2 study testing Temozolomide in people with Leukemia, Myeloid, run by Bruno C. Medeiros at 1 site in United States.
Trial summary
Open-label, non-randomized, parallel assignment, phase 2 trial assessing the safety and efficacy of distinct temozolomide treatment regimens for patients with AML and poor prognosis Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Leukemia, Myeloid
- What is being tested?
- Temozolomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Jan 2010
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed Acute Myeloid Leukemia, as defined by the WHO classification.
- Patients must be considered unfit for conventional induction chemotherapy, unwilling to receive such treatment or have evidence of disease relapse or refractory disease.
- For patients who have received no prior conventional chemotherapy, one of the following must be present:
- Poor risk cytogenetics (complex abnormalities, deletions of chromosome 7 or 5, 11q23 abnormalities, inv[3])
- Secondary leukemia (prior hematologic disorder or therapy-related leukemia).
- Age > 60 years of age.
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- Life expectancy of greater than 3 months.
- ECOG performance status greater than 2.
- Patients must have normal organ and marrow function as defined below:
- Adequate hepatic function: Total bilirubin 1.5mg/dL, AST(SGOT)/ALT(SGPT) 2.5 X institutional upper limit of normal.
- Adequate renal function: serum creatinine within normal institutional limits or Calculated creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or DTIC
- History of gastrointestinal disease or significant bowel resection that could interfere with drug absorption.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Prior allogeneic stem cell transplantation.
- Inability to swallow tablets
- Prior radiation up to more than 25% of bone marrow.
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Phase II Study of Two Distinct Tailored Temozolomide Regimens for Patients With Acute Myeloid Leukemia Age > 60 Years and Poor Risk/Refractory Disease
Open-label, non-randomized, parallel assignment, phase 2 trial assessing the safety and efficacy of distinct temozolomide treatment regimens for patients with AML and poor prognosis
Read the detailed description
This is a single institution phase 2 clinical trial evaluating the efficacy, safety, and tolerability of tailored temozolomide therapy for patients with acute myeloid leukemia (AML) and poor risk features.
Patients will be assigned to 1 of 2 parallel treatment groups based on their AGAT promoter region methylation status, as determined by PCR.
Patients achieving a complete remission after 1 to 2 cycles of chemotherapy will be eligible to receive up to an additional 5 cycles of temozolomide of 5 or 19 days, depending on the methylation status of the AGAT promoter (consolidation phase).
- Conditions
- Leukemia, Myeloid
- Being tested
- Temozolomide
- Medical subject headings
- Leukemia, Myeloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TemozolomideDrug
Also called Temodar, Temodal
Priming, Group 2 only, 100 mg/m2/day temozolomide.
Induction (both arms) 200 mg/m2/day temozolomide
| Study group | Role | What they receive |
|---|---|---|
| Methylated AGAT Promoter (Group 1) | Experimental | Induction: 200 mg/m2/day oral Temozolomide x 7 days Receives: Drug: Temozolomide |
| Un-Methylated AGAT Promoter (Group 2) | Experimental | Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days Receives: Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate (CR + CRi + LFS)
Response determined per European LeukemiaNet response criteria:
CR = bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0 x 10e9/L; platelet count > 100 x 10e9/L; and independence of red cell transfusions.
CRi = all CR criteria except for residual neutropenia (< 1.0 x 10e9/L) or thrombocytopenia (< 100 x 10e9/L)].
Morphologic leukemia-free state (LFS) = bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; with no hematologic recovery required.
Relapse = bone marrow blasts >5%; reappearance of blasts in the blood; or development of extramedullary disease.
Measured: up to 2 months
Secondary outcomes (2)
Toxicity Profile: Total Number of Drug-related Serious Adverse Events
Measured: 12 months
Toxicity Profile: Individual Subjects With Drug-related SAEs
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2008 (estimated)
- Study startDec 2007
- Primary completionDec 2009
- Study completionJan 2010
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Leukemia, MyeloidStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bruno C. Medeiros
- Sponsor type
- University, hospital or other
- Collaborators
- Schering-Plough
- Responsible party
- Sponsor-investigator, Bruno C. Medeiros, Stanford University
- Investigators
- Bruno Carneiro de Medeiros, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00611247
- Sponsor's protocol ID
- IRB-07815
- Other IDs
- 97611, SU-12142007-936, HEMAML0004
- Status last verified
- May 2018
- First submitted
- 25 Jan 2008
- Last updated
- 15 Jun 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Medeiros BC, Kohrt HE, Gotlib J, Coutre SE, Zhang B, Arber DA, Zehnder JL. Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia. Am J Hematol. 2012 Jan;87(1):45-50. doi: 10.1002/ajh.22191. Epub 2011 Nov 4.
PubMed 22052619Bruno C Medeiros, Holbrook E Kohrt, Richa Rajwanshi, Jason Gotlib, Steven E Coutre, Michaela Liedtke, Caroline Berube, Melody Zhang, Daniel A Arber, James L Zehnder. "Temozolomide In Acute Myeloid Leukemia: A MGMT Promoter Methylation Status-Based Treatment Stratification." Blood. 2010;116(21) (abs 3313).
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Two Distinct Tailored Temozolomide Regimens for Patients With Acute Myeloid Leukemia Age > 60 Years and Poor Risk/Refractory Disease
- ClinicalTrials.gov ID
- NCT00611247
- Acronym / sponsor ID
- IRB-07815
- Conditions
- Leukemia, Myeloid
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Bruno C. MedeirosUniversity, hospital or other
- Collaborators
- Schering-Plough
- Study start
- Dec 2007
- Primary completion
- Dec 2009 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 8 Feb 2008 (estimated)
- Results
- Posted 9 Jul 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Open-label, non-randomized, parallel assignment, phase 2 trial assessing the safety and efficacy of distinct temozolomide treatment regimens for patients with AML and poor prognosis
Detailed description
This is a single institution phase 2 clinical trial evaluating the efficacy, safety, and tolerability of tailored temozolomide therapy for patients with acute myeloid leukemia (AML) and poor risk features.
Patients will be assigned to 1 of 2 parallel treatment groups based on their AGAT promoter region methylation status, as determined by PCR.
Patients achieving a complete remission after 1 to 2 cycles of chemotherapy will be eligible to receive up to an additional 5 cycles of temozolomide of 5 or 19 days, depending on the methylation status of the AGAT promoter (consolidation phase).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Methylated AGAT Promoter (Group 1) | Experimental | Drug: TemozolomideInduction: 200 mg/m2/day oral Temozolomide x 7 days |
| Un-Methylated AGAT Promoter (Group 2) | Experimental | Drug: TemozolomidePriming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients must have histologically or cytologically confirmed Acute Myeloid Leukemia, as defined by the WHO classification.
- Patients must be considered unfit for conventional induction chemotherapy, unwilling to receive such treatment or have evidence of disease relapse or refractory disease.
- For patients who have received no prior conventional chemotherapy, one of the following must be present:
- Age > 60 years of age.
- Life expectancy of greater than 3 months.
Key exclusion criteria (8 listed)
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- Patients may not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or DTIC
- History of gastrointestinal disease or significant bowel resection that could interfere with drug absorption.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| TemozolomideAlso: Temodar, TemodalPriming, Group 2 only, 100 mg/m2/day temozolomide. Induction (both arms) 200 mg/m2/day temozolomide | Drug | Methylated AGAT Promoter (Group 1), Un-Methylated AGAT Promoter (Group 2) |
Primary outcome
Response Rate (CR + CRi + LFS)
Time frame: up to 2 months
Response determined per European LeukemiaNet response criteria: CR = bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0 x 10e9/L; platelet count > 100 x 10e9/L; and independence of red cell transfusions. CRi = all CR criteria except for residual neutropenia (< 1.0 x 10e9/L) or thrombocytopenia (< 100 x 10e9/L)]. Morphologic leukemia-free state (LFS) = bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; with no hematologic recovery required. Relapse = bone marrow blasts >5%; reappearance of blasts in the blood; or development of extramedullary disease.
2 secondary outcomes
Toxicity Profile: Total Number of Drug-related Serious Adverse Events
Time frame: 12 months
Toxicity Profile: Individual Subjects With Drug-related SAEs
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22052619Medeiros BC, Kohrt HE, Gotlib J, Coutre SE, Zhang B, Arber DA, Zehnder JL. Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia. Am J Hematol. 2012 Jan;87(1):45-50. doi: 10.1002/ajh.22191. Epub 2011 Nov 4.
- Results publicationBruno C Medeiros, Holbrook E Kohrt, Richa Rajwanshi, Jason Gotlib, Steven E Coutre, Michaela Liedtke, Caroline Berube, Melody Zhang, Daniel A Arber, James L Zehnder. "Temozolomide In Acute Myeloid Leukemia: A MGMT Promoter Methylation Status-Based Treatment Stratification." Blood. 2010;116(21) (abs 3313).
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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.
Bruno Carneiro de Medeiros principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Temozolomide in people with Leukemia, Myeloid, run by Bruno C. Medeiros 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 12 inclusion and 8 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 15 Jun 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 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 9 Jul 2014). 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?
Response Rate (CR + CRi + LFS) (time frame: up to 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00611247, which also lists 2 linked publications.
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 15 Jun 2018.