Leukemia, Acute MyeloidPhase 2TALLNCT00687323
Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression (P05052)
A Phase 2 study testing temozolomide in people with Leukemia, Acute Myeloid and Myelodysplastic Syndrome, run by Merck Sharp & Dohme LLC.
Trial summary
The primary objective of this study is to evaluate the safety, tolerability, and efficacy of temozolomide in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) participants who are not candidates for standard induction therapy and exhibit low MGMT expression. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Acute Myeloid, Myelodysplastic Syndrome
- 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
- 47 participants
- Where
- No sites listed yet
- Study dates
- 30 Jul 2007to 23 Dec 2012
- 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
- Confirmed diagnosis of acute myeloid leukemia (AML), any subtype except acute promyelocytic leukemia (APL), by the World Health Organization (WHO) criteria, or high risk MDS with blasts between 10 and 20% in the bone marrow.
- No prior AML chemotherapy except hydroxyurea.
- Leukemic blast count <30x10^9/L at the start of therapy. Prior cytoreduction with hydroxyurea (maximum 14 days) is permitted.
- Participant is not a candidate for aggressive induction based on at least one of the following: adverse-risk cytogenetics (complete or partial deletion of 5 or 7, complex [>3] cytogenetic abnormalities, inv3, 11q23 abnormalities); secondary AML (antecedent hematologic disorder or therapy-related AML); comorbid medical illnesses precluding standard induction therapy; participant's refusal of standard induction therapy.
- Confirmed low MGMT expression (MGMT: beta-actin ≤0.2), as evaluated by Western blot, or weak MGMT expression defined as > 0.2 and ≤2.5 if promoter is methylated, upon Sponsor approval.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Use of medically approved contraception in fertile males and females.
- Negative urine or serum pregnancy test for women of childbearing potential (72 hours prior to Baseline).
Who cannot join
- Serum bilirubin >2 times the upper limit of normal (ULN), or serum aspartate aminotransferase/ alanine aminotransferase >5 times ULN.
- Serum creatinine >200 umol/L.
- History of other malignancies within 1 year prior to study entry, with the exception of localized nonmelanomatous skin cancer or cervical cancer in situ.
- Presence of active uncontrolled infection.
- Known human immunodeficiency virus (HIV) infection.
- Any medical condition that may interfere with protocol evaluation or oral medication intake.
- Prior chemotherapy other than hydroxyurea.
About this study
Official title: Phase II Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) Subjects Unsuitable for Standard Induction Therapy Exhibiting Low MGMT Expression
The primary objective of this study is to evaluate the safety, tolerability, and efficacy of temozolomide in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) participants who are not candidates for standard induction therapy and exhibit low MGMT expression.
- Conditions
- Leukemia, Acute Myeloid, Myelodysplastic Syndrome
- Being tested
- temozolomide
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
temozolomideDrug
Also called Temodol, SCH 052365, MK-7365
| Study group | Role | What they receive |
|---|---|---|
| Temozolomide | Experimental | Temozolomide capsules orally, once daily: 1 induction cycle (200 mg/m^2/day for 7 days in 1 28 day cycle), 1 consolidation cycle (200 mg/m^2/day for 7 days in 1 28 day cycle), then 200 mg/m^2/day for 7 days each 28-day cycle or for 5 days each 28-day cycle (12 cycle maximum). Alternatively participants could have received 100 mg/m^2/day for 21 days of each 28-day cycle (12 cycle maximum). Receives: Drug: temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Response at the End of Temozolomide Induction
Complete Response (CR): < 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) > 1.0 x 10^9/L, platelets > 100 x 10^9/L, and no extramedullary disease.
CR with incomplete platelet recovery (CRp): All the criteria of CR but with platelets < 100 x 10^9/L but ≥ 50 x 10^9/L and platelet transfusion independent.
Morphologic leukemia-free state (MLFS): complete clearance of blasts from marrow and blood, but criteria for CR or CRp not met.
Partial response (PR): decrease ≥ 50% BM blasts. Minimal Response (MR): decrease ≥ 25% but <50% BM blasts.
Measured: at the end of each cycle (approximately 4 weeks post start of cycle), up to a maximum 63 weeks
Secondary outcomes (10)
Duration of Response in Participants Achieving Complete Response (CR) and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide
Complete Response (CR): < 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) > 1.0 x 10^9/L, platelets > 100 x 10^9/L, and no extramedullary disease.
Measured: Up to 1 year after treatment ends (up to 115 weeks)
Relapse-free Survival in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide
Relapse-free survival was defined as time to disease progression. Complete Response (CR): < 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) > 1.0 x 10^9/L, platelets > 100 x 10^9/L, and no extramedullary disease. CR with incomplete platelet recovery (CRp): All the criteria of CR but with platelets < 100 x 10^9/L but ≥ 50 x 10^9/L and platelet transfusion independent.
Measured: Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)]
Overall Survival (OS) in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide
OS was defined as the time from start of treatment until death or end of study.
Complete Response (CR): < 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) > 1.0 x 10^9/L, platelets > 100 x 10^9/L, and no extramedullary disease. CR with incomplete platelet recovery (CRp): All the criteria of CR but with platelets < 100 x 10^9/L but ≥ 50 x 10^9/L and platelet transfusion independent.
Measured: Start of treatment until death or end of study [up to 1 year after treatment ends (up to 115 weeks)]
Number of Previously Untreated Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression
Low MGMT expression was defined as MGMT/β-actin ratio < 0.2. MGMT \& β-actin are cancer biomarkers.
Measured: Baseline
MGMT Expression in Leukemic Blasts at the Time of Relapse
Low MGMT expression was defined as MGMT/β-actin ratio of <0.2.
MGMT \& β-actin are cancer biomarkers.
Measured: Up to 1 year after treatment ends (up to 115 weeks)
Number of Participants With CR, PR, or MLFS Who Received Modified Low Dose Maintenance Therapy (100 mg/m^2/Day x21 Days of Each 28 Day Cycle) and Experienced Toxicity
Toxicity was defined as any adverse event experienced by a participant regardless of causal relationship with study treatment. An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which did not necessarily have a causal relationship with the treatment. Adverse events may have included the onset of new illness and/or the exacerbation of preexisting conditions.
Measured: From first dose to 30 days after last dose of study drug (up to 67 weeks)
Progression-free Survival for Participants Achieving PR, MLSF, or MR
Progression-free survival was defined as time to disease progression. Morphologic leukemia-free state (MLFS): complete clearance of blasts from marrow and blood, but criteria for CR or CRp not met. Partial response (PR): decrease ≥ 50% BM blasts. Minimal Response (MR): decrease ≥ 25% but <50% BM blasts.
Measured: Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)]
Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30
The EORTC QLQ-C30 was a 30-item questionnaire developed to assess the QoL of cancer patients. Scores ranged from 0 -100. For functional and global QoL scales, higher scores meant a better level of function. For symptom-oriented scales, a higher score meant more severe symptoms and a decrease in QoL.
Measured: Baseline and post-study visit (63 weeks)
Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by EORTC QLQ-LC13
The EORTC QLQ-LC13 was a 13-item questionnaire developed to supplement the EORTC QLQ-C30 in lung cancer patients. It had a score range 0-100 with higher scores representing an increase in symptoms.
Measured: Baseline and post-study visit (63 weeks)
Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by Functional Assessment of Cancer Therapy (FACT)-G
The FACT-G was a 27-item questionnaire developed to assess the QoL in patients with chronic illnesses. Scores ranged from 0 to 28. For physical well being, lower scores indicated a better outcome. For functional well being, higher scores indicated a better outcome. For social \& emotional well being, whether a high score or a lower one indicated a better outcome depended on the question.
Measured: Baseline and post-study visit (63 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2008 (estimated)
- Study start30 Jul 2007
- Primary completion9 May 2011
- Study completion23 Dec 2012
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 (1)Papers the sponsor has linked to this study.
- Other trials for Leukemia, Acute MyeloidStudies of the same condition, open and under way.
- More trials run by Merck Sharp & Dohme LLCThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck Sharp & Dohme LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00687323
- Sponsor's protocol ID
- P05052
- Other IDs
- MK-7365-240
- Acronym
- TALL
- Status last verified
- May 2017
- First submitted
- 27 May 2008
- Last updated
- 7 Jun 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final\_Updated%20July\_9\_2014.pdf http://engagezone.msd.com/ds\_documentation.php
Publications
Brandwein JM, Yang L, Schimmer AD, Schuh AC, Gupta V, Wells RA, Alibhai SM, Xu W, Minden MD. A phase II study of temozolomide therapy for poor-risk patients aged >or=60 years with acute myeloid leukemia: low levels of MGMT predict for response. Leukemia. 2007 Apr;21(4):821-4. doi: 10.1038/sj.leu.2404545. Epub 2007 Jan 25. No abstract available.
PubMed 17252015
Study at a glance
From the registry record, last updated by the sponsor on 7 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) Subjects Unsuitable for Standard Induction Therapy Exhibiting Low MGMT Expression
- ClinicalTrials.gov ID
- NCT00687323
- Acronym / sponsor ID
- TALL / P05052
- Conditions
- Leukemia, Acute Myeloid, Myelodysplastic Syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
- Study start
- 30 Jul 2007 (actual)
- Primary completion
- 9 May 2011 (actual)
- Study completion
- 23 Dec 2012 (actual)
- First posted
- 30 May 2008 (estimated)
- Results
- Posted 18 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the safety, tolerability, and efficacy of temozolomide in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) participants who are not candidates for standard induction therapy and exhibit low MGMT expression.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Temozolomide | Experimental | Drug: temozolomideTemozolomide capsules orally, once daily: 1 induction cycle (200 mg/m^2/day for 7 days in 1 28 day cycle), 1 consolidation cycle (200 mg/m^2/day for 7 days in 1 28 day cycle), then 200 mg/m^2/day for 7 days each 28-day cycle or for 5 days each 28-day cycle (12 cycle maximum). Alternatively participants could have received 100 mg/m^2/day for 21 days of each 28-day cycle (12 cycle maximum). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmed diagnosis of acute myeloid leukemia (AML), any subtype except acute promyelocytic leukemia (APL), by the World Health Organization (WHO) criteria, or high risk MDS with blasts between 10 and 20% in the bone marrow.
- No prior AML chemotherapy except hydroxyurea.
- Leukemic blast count <30x10^9/L at the start of therapy. Prior cytoreduction with hydroxyurea (maximum 14 days) is permitted.
- Participant is not a candidate for aggressive induction based on at least one of the following: adverse-risk cytogenetics (complete or partial deletion of 5 or 7, complex [>3] cytogenetic abnormalities, inv3, 11q23 abnormalities); secondary AML (antecedent hematologic disorder or therapy-related AML); comorbid medical illnesses precluding standard induction therapy; participant's refusal of standard induction therapy.
- Confirmed low MGMT expression (MGMT: beta-actin ≤0.2), as evaluated by Western blot, or weak MGMT expression defined as > 0.2 and ≤2.5 if promoter is methylated, upon Sponsor approval.
Key exclusion criteria (7 listed)
- Serum bilirubin >2 times the upper limit of normal (ULN), or serum aspartate aminotransferase/ alanine aminotransferase >5 times ULN.
- Serum creatinine >200 umol/L.
- History of other malignancies within 1 year prior to study entry, with the exception of localized nonmelanomatous skin cancer or cervical cancer in situ.
- Presence of active uncontrolled infection.
- Known human immunodeficiency virus (HIV) infection.
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: Temodol, SCH 052365, MK-7365 | Drug | Temozolomide |
Primary outcome
Clinical Response at the End of Temozolomide Induction
Time frame: at the end of each cycle (approximately 4 weeks post start of cycle), up to a maximum 63 weeks
Complete Response (CR): < 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) > 1.0 x 10^9/L, platelets > 100 x 10^9/L, and no extramedullary disease. CR with incomplete platelet recovery (CRp): All the criteria of CR but with platelets < 100 x 10^9/L but ≥ 50 x 10^9/L and platelet transfusion independent. Morphologic leukemia-free state (MLFS): complete clearance of blasts from marrow and blood, but criteria for CR or CRp not met. Partial response (PR): decrease ≥ 50% BM blasts. Minimal Response (MR): decrease ≥ 25% but <50% BM blasts.
10 secondary outcomes
Duration of Response in Participants Achieving Complete Response (CR) and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide
Time frame: Up to 1 year after treatment ends (up to 115 weeks)
Relapse-free Survival in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide
Time frame: Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)]
Overall Survival (OS) in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide
Time frame: Start of treatment until death or end of study [up to 1 year after treatment ends (up to 115 weeks)]
Number of Previously Untreated Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression
Time frame: Baseline
MGMT Expression in Leukemic Blasts at the Time of Relapse
Time frame: Up to 1 year after treatment ends (up to 115 weeks)
Number of Participants With CR, PR, or MLFS Who Received Modified Low Dose Maintenance Therapy (100 mg/m^2/Day x21 Days of Each 28 Day Cycle) and Experienced Toxicity
Time frame: From first dose to 30 days after last dose of study drug (up to 67 weeks)
Progression-free Survival for Participants Achieving PR, MLSF, or MR
Time frame: Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)]
Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30
Time frame: Baseline and post-study visit (63 weeks)
Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by EORTC QLQ-LC13
Time frame: Baseline and post-study visit (63 weeks)
Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by Functional Assessment of Cancer Therapy (FACT)-G
Time frame: Baseline and post-study visit (63 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jun 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 17252015Brandwein JM, Yang L, Schimmer AD, Schuh AC, Gupta V, Wells RA, Alibhai SM, Xu W, Minden MD. A phase II study of temozolomide therapy for poor-risk patients aged >or=60 years with acute myeloid leukemia: low levels of MGMT predict for response. Leukemia. 2007 Apr;21(4):821-4. doi: 10.1038/sj.leu.2404545. Epub 2007 Jan 25. No abstract available.
- Individual participant dataSharing planned: Yes. http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf http://engagezone.msd.com/ds_documentation.php
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing temozolomide in people with Leukemia, Acute Myeloid and Myelodysplastic Syndrome, run by Merck Sharp & Dohme LLC.
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 8 inclusion and 7 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 7 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
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 18 Jul 2012). 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?
Clinical Response at the End of Temozolomide Induction (time frame: at the end of each cycle (approximately 4 weeks post start of cycle), up to a maximum 63 weeks). 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 NCT00687323, which also lists 1 linked publication.
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 7 Jun 2017.