Childhood Acute Myeloblastic Leukemia With Maturation (M2)Phase 1NCT00042796
Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia
A Phase 1 study testing decitabine, pharmacological study and laboratory biomarker analysis in people with Childhood Acute Myeloblastic Leukemia With Maturation (M2) and Childhood Acute Promyelocytic Leukemia (M3), run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. This phase I trial is studying the side effects and best dose of decitabine in treating children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Promyelocytic Leukemia (M3), Recurrent Childhood Acute Lymphoblastic Leukemia
- What is being tested?
- decitabine, pharmacological study and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2002to Oct 2005
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Histologically confirmed acute myeloid leukemia (AML) or acute lymphoblastic leukemia that is considered refractory to conventional therapy or for which no conventional therapy exists
- For patients with AML:
- M3 marrow
- M2 marrow with at least 15% blasts
- Secondary AML allowed
- CNS involvement allowed
Show all 48Show fewer
- Performance status - Karnofsky 50-100% (age 17 to 21)
- Performance status - Lansky 50-100% (age 16 and under)
- At least 8 weeks
- See Chemotherapy
- WBC no greater than 30,000/mm^3
- Patients with granulocytopenia, anemia, and/or thrombocytopenia are eligible but are not evaluable for hematological toxicity
- Bilirubin no greater than 1.5 times normal
- ALT no greater than 5 times normal
- Albumin at least 2 g/dL
- Creatinine no greater than 1.5 times normal
- Creatinine clearance or radioisotope glomerular filtration rate at least lower limit of normal
- Shortening fraction at least 27% by echocardiogram
- Ejection fraction at least 50% by MUGA scan
- No evidence of dyspnea at rest
- No exercise intolerance
- Oxygen saturation greater than 94% by pulse oximetry
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- Concurrent seizure disorder allowed if well controlled on anticonvulsants
- No grade 2 or greater CNS toxicity
- No uncontrolled infection (i.e., infections associated with fever, dissemination, hemodynamic instability [requiring pressor support], and progression while on therapy)
- No active graft-versus-host disease (GVHD)
- GVHD well controlled on cyclosporine allowed
- Recovered from prior immunotherapy
- At least 1 week since prior biologic agents
- At least 6 months since prior allogeneic bone marrow transplantation (BMT)
- At least 3 months since prior autologous BMT
- No concurrent sargramostim (GM-CSF)
- No concurrent prophylactic filgrastim (G-CSF) during the first course of therapy
- Recovered from prior chemotherapy
- At least 4 weeks since prior cytarabine
- At least 24 hours since prior cytoreductive therapy with hydroxyurea (20-30 mg/kg/day for no more than 7 days) to lower the WBC to no greater than 30,000/mm^3
- No concurrent intrathecal therapy during the first course of decitabine
- Recovered from prior radiotherapy
- At least 2 weeks since prior local palliative radiotherapy (small port)
- At least 6 weeks since prior cranial or craniospinal radiotherapy
- No concurrent medications that induce cytidine deaminase or deoxycytidine kinase (e.g., cytarabine)
- No concurrent medications that mask poor or deteriorating organ function
- No concurrent CNS prophylaxis during the first course of decitabine
- Concurrent anticonvulsants with no known interactions with decitabine allowed
- Concurrent antibacterial or antifungal therapies for controlled infections allowed
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Oncology Group
Arcadia, California, 91006-3776
About this study
Official title: A Phase I Study Of Decitabine (DAC) (IND # 50733) In Children With Relapsed Or Refractory Acute Leukemia
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. This phase I trial is studying the side effects and best dose of decitabine in treating children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of decitabine that is associated with consistent evidence of deoxyribonucleic acid (DNA) demethylation in children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia.
II. Determine the dose-limiting toxicity, pharmacokinetics, and antitumor activity of this drug in these patients.
III. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global and specific DNA methylation status (using methylation microarrays) and hemoglobin F levels in these patients.
IV. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global changes in gene expression profiles using cDNA microarrays and drug sensitivity of blast cells by MTT assays in these patients.
- Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, deletions and single nucleotide polymorphisms in genomic DNA of deoxycytidine kinase and cytidine deaminase genes in these patients.
VI. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, acetylation and methylation of histones H3 and H4 and helicase protein expression in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease type (acute myeloid leukemia vs acute lymphoblastic leukemia).
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 4-6 weeks for a minimum of 4 courses 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 15-21 patients will be accrued for this study within 7.5-21 months.
- Conditions
- Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Promyelocytic Leukemia (M3), Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia
- Being tested
- decitabine, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
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
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (decitabine) | Experimental | Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 4-6 weeks for a minimum of 4 courses in the absence of disease progression or unacceptable toxicity. Receives: Drug: decitabine; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD defined as the highest dose at which fewer than one-third of patients experience DLT assessed using CTC version 2.0
Measured: 4 weeks
Secondary outcomes (6)
CR rate
Will be estimated by proportions.
Measured: Up to 3 years
PR rate
Will be estimated by proportions.
Measured: Up to 3 years
DNA methylation
Pearson correlation will be used.
Measured: Up to 3 years
Gene expression profiles
Will be analyzed using hierarchical clustering.
Measured: Up to 3 years
HDAC/HAT activity
Pearson correlation coefficient analysis will be used.
Measured: Up to 3 years
Presence of mutant helicases
Measured: Up to 3 years
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 startDec 2002
- Primary completionOct 2005
Why it stopped: Administratively complete.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Childhood Acute Myeloblastic Leukemia With Maturation (M2)Studies 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
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Norman Lacayo, Principal investigator, Children's Oncology Group
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00042796
- Sponsor's protocol ID
- NCI-2012-01873
- Other IDs
- ADVL0114, U01CA097452, CDR0000069471
- Status last verified
- Jan 2013
- First submitted
- 5 Aug 2002
- Last updated
- 23 Jan 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Of Decitabine (DAC) (IND # 50733) In Children With Relapsed Or Refractory Acute Leukemia
- ClinicalTrials.gov ID
- NCT00042796
- Acronym / sponsor ID
- NCI-2012-01873
- Conditions
- Childhood Acute Myeloblastic Leukemia With Maturation (M2), Childhood Acute Promyelocytic Leukemia (M3), Recurrent Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood Acute Myeloid Leukemia, Secondary Acute Myeloid Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Administratively complete.
- Enrolment
- 21 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Dec 2002
- Primary completion
- Oct 2005 (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.
Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. This phase I trial is studying the side effects and best dose of decitabine in treating children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of decitabine that is associated with consistent evidence of deoxyribonucleic acid (DNA) demethylation in children with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia.
II. Determine the dose-limiting toxicity, pharmacokinetics, and antitumor activity of this drug in these patients.
III. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global and specific DNA methylation status (using methylation microarrays) and hemoglobin F levels in these patients.
IV. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, global changes in gene expression profiles using cDNA microarrays and drug sensitivity of blast cells by MTT assays in these patients.
- Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, deletions and single nucleotide polymorphisms in genomic DNA of deoxycytidine kinase and cytidine deaminase genes in these patients.
VI. Determine the biologic correlates of decitabine-induced DNA demethylation by characterizing, before and after treatment, acetylation and methylation of histones H3 and H4 and helicase protein expression in these patients.
OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to disease type (acute myeloid leukemia vs acute lymphoblastic leukemia).
Patients receive decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 4-6 weeks for a minimum of 4 courses 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 at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 15-21 patients will be accrued for this study within 7.5-21 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: pharmacological study, Other: laboratory biomarker analysisPatients receive decitabine IV over 1 hour on days 1-5 and 8-12. Treatment repeats every 4-6 weeks for a minimum of 4 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (48 listed)
- Histologically confirmed acute myeloid leukemia (AML) or acute lymphoblastic leukemia that is considered refractory to conventional therapy or for which no conventional therapy exists
- For patients with AML:
- CNS involvement allowed
- Performance status - Karnofsky 50-100% (age 17 to 21)
- Performance status - Lansky 50-100% (age 16 and under)
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) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (decitabine) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (decitabine) |
Primary outcome
MTD defined as the highest dose at which fewer than one-third of patients experience DLT assessed using CTC version 2.0
Time frame: 4 weeks
6 secondary outcomes
CR rate
Time frame: Up to 3 years
PR rate
Time frame: Up to 3 years
DNA methylation
Time frame: Up to 3 years
Gene expression profiles
Time frame: Up to 3 years
HDAC/HAT activity
Time frame: Up to 3 years
Presence of mutant helicases
Time frame: Up to 3 years
Results and safety
The study was stopped early (reason given: Administratively complete.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2013.
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.
Norman Lacayo principal investigator
Children's Oncology Group
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, pharmacological study and laboratory biomarker analysis in people with Childhood Acute Myeloblastic Leukemia With Maturation (M2) and Childhood Acute Promyelocytic Leukemia (M3), run by National Cancer Institute (NCI) 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 48 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 23 Jan 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 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 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 (reason given: Administratively complete.). 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?
MTD defined as the highest dose at which fewer than one-third of patients experience DLT assessed using CTC version 2.0 (time frame: 4 weeks). 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 23 Jan 2013.