Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesPhase 1NCT00049582
Decitabine in Treating Patients With Myelodysplastic Syndromes or Acute Myeloid Leukemia
A Phase 1 study testing decitabine, laboratory biomarker analysis and pharmacological study in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), run by National Cancer Institute (NCI) at 1 site in Canada.
Trial summary
This phase I trial is studying the side effects and best dose of decitabine in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
- What is being tested?
- decitabine, laboratory biomarker analysis and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteCanada
- Study dates
- Sep 2002to Jun 2010
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- One of the following diagnoses:
- High-risk myelodysplastic syndromes (MDS)
- Acute myeloid leukemia (AML)
- De novo, secondary, or relapsed disease
- Any number of prior regimens for primary or relapsed disease
- Ineligible for or refuses aggressive management
Show all 41Show fewer
- Measurable disease, defined as:
- More than 5% blasts in bone marrow of patients with MDS
- More than 30% blasts in bone marrow of patients with AML
- Involvement of cerebrospinal fluid allowed
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- See Disease Characteristics
- Bilirubin no greater than 1.25 times upper limit of normal (ULN)
- AST and/or ALT no greater than 1.25 times ULN
- Creatinine less than 1.7 mg/dL
- Creatinine clearance at least 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No ongoing or active infection
- No other uncontrolled illness that would preclude study participation
- No psychiatric illness or social situation that would preclude study compliance
- No prior allergic reactions to compounds of similar chemical or biological composition to decitabine
- No other active malignancy
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- At least 4 weeks since prior biologic therapy (e.g., interferon, filgrastim [G-CSF], sargramostim [GM-CSF], thrombopoietin, or epoetin alfa)
- No concurrent hematopoietic growth factors (GM-CSF, thrombopoietin, or epoetin alfa)
- No concurrent prophylactic G-CSF
- Prior intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement
- At least 4 weeks since prior chemotherapy (except low-dose chemotherapy administered to maintain WBC counts) (6 weeks for nitrosoureas or mitomycin) and recovered
- At least 24 hours since prior hydroxyurea
- Concurrent intrathecal cytarabine allowed for patients with cerebrospinal fluid involvement
- No prior radiotherapy greater than 3,000 cGy to marrow-producing areas
- At least 4 weeks since prior radiotherapy and recovered
- Prior investigational therapy allowed
- No other concurrent investigational agents
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer therapy
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
Canada1 site
Princess Margaret Hospital Phase 2 Consortium
Toronto, Ontario, M5G 2M9
About this study
Official title: Phase I Study of 5-Aza-2'-Deoxycytidine (Decitabine) as a Biologic Modifier of Retinoid Responsive Genes in Patients With High-Risk Myelodysplastic Syndromes and Acute Myelogenous Leukemia (De-novo, Relapsed or Secondary)
This phase I trial is studying the side effects and best dose of decitabine in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
Read the detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of decitabine in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia.
II. Determine the minimum effective dose of this drug that produces demethylation of DNA with tolerable toxicity in these patients.
III. Determine the minimum effective dose of this drug that augments in vitro responses to retinoids.
IV. Determine the pharmacokinetics of this drug in these patients. V. Determine the clinical response rate of patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 18 months.
- Conditions
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
- Being tested
- decitabine, laboratory biomarker analysis, pharmacological study
- Medical subject headings
- Congenital Abnormalities, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Myeloproliferative Disorders, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
decitabineDrug
Also called 5-aza-dCyd, 5AZA, DAC
Given IV
laboratory biomarker analysisOther
Correlative studies
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (decitabine) | Experimental | Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of decitabine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. Receives: Drug: decitabine; Other: laboratory biomarker analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Measured: Up to day 28
Secondary outcomes (4)
Minimal effective dose of decitabine that will lead to demethylation of deoxyribonucleic acid (DNA) with tolerable toxicity as assessed by RXR gene
Measured: Up to day 28
Proportion of patients with in-vitro retinoid response
Measured: Up to 8 years
Duration of clinical response
Measured: Up to 8 years
Changes in gene expression, gene methylation and bone marrow aspirate sample measurements
The effect on gene expression due to pharmacological exposures (ie retinoic acid receptor [RAR] or retinoid X receptor [RXR]) will be assessed using chi-square tests.
Measured: Up to day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study startSep 2002
- Primary completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mark Minden, Principal investigator, Princess Margaret Hospital Phase 2 Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00049582
- Sponsor's protocol ID
- NCI-2012-02502
- Other IDs
- NCI-2012-02502, CDR0000258121, NCI-5591, PHL-004, PHL-004, 5591, N01CM62203
- Status last verified
- Sep 2013
- First submitted
- 12 Nov 2002
- Last updated
- 30 Sep 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of 5-Aza-2'-Deoxycytidine (Decitabine) as a Biologic Modifier of Retinoid Responsive Genes in Patients With High-Risk Myelodysplastic Syndromes and Acute Myelogenous Leukemia (De-novo, Relapsed or Secondary)
- ClinicalTrials.gov ID
- NCT00049582
- Acronym / sponsor ID
- NCI-2012-02502
- Conditions
- Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2002
- Primary completion
- Jun 2010 (actual)
- First posted
- 27 Jan 2003 (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 phase I trial is studying the side effects and best dose of decitabine in treating patients with myelodysplastic syndromes or acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die.
Detailed description
OBJECTIVES:
- Determine the maximum tolerated dose of decitabine in patients with high-risk myelodysplastic syndromes or acute myeloid leukemia.
II. Determine the minimum effective dose of this drug that produces demethylation of DNA with tolerable toxicity in these patients.
III. Determine the minimum effective dose of this drug that augments in vitro responses to retinoids.
IV. Determine the pharmacokinetics of this drug in these patients. V. Determine the clinical response rate of patients treated with this drug.
OUTLINE: This is a dose-escalation, multicenter study.
Patients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of decitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A maximum of 36 patients will be accrued for this study within 18 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (decitabine) | Experimental | Drug: decitabine, Other: laboratory biomarker analysis, Other: pharmacological studyPatients receive decitabine IV over 3 hours twice daily OR IV over 1 hour once daily on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of decitabine until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (41 listed)
- One of the following diagnoses:
- Ineligible for or refuses aggressive management
- Measurable disease, defined as:
- Involvement of cerebrospinal fluid allowed
- Performance status - ECOG 0-2
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| decitabineAlso: 5-aza-dCyd, 5AZA, DACGiven IV | Drug | Treatment (decitabine) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (decitabine) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (decitabine) |
Primary outcome
Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0
Time frame: Up to day 28
4 secondary outcomes
Minimal effective dose of decitabine that will lead to demethylation of deoxyribonucleic acid (DNA) with tolerable toxicity as assessed by RXR gene
Time frame: Up to day 28
Proportion of patients with in-vitro retinoid response
Time frame: Up to 8 years
Duration of clinical response
Time frame: Up to 8 years
Changes in gene expression, gene methylation and bone marrow aspirate sample measurements
Time frame: Up to day 5
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2013.
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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.
Mark Minden principal investigator
Princess Margaret Hospital Phase 2 Consortium
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 decitabine, laboratory biomarker analysis and pharmacological study in people with Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities and Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), run by National Cancer Institute (NCI) 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 41 inclusion and 0 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 30 Sep 2013. 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 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?
The study was stopped early. Results are not available in the source record.
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?
Maximum tolerated dose (MTD) of decitabine, graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 (time frame: Up to day 28). 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 30 Sep 2013.