Leukemia, Myeloid, AcutePhase 1AMLNCT01001143
Intravenous (IV) Decitabine and Oral Bexarotene for Acute Myelogenous Leukemia (AML)
A Phase 1 study testing Decitabine and Bexarotene in people with Leukemia, Myeloid, Acute, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The main objective is to determine the safety and tolerability of combination decitabine and bexarotene during four cycles of therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- Decitabine and Bexarotene
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to May 2014
- 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
- AML with bone marrow blasts ≥ 20%.
- Relapsed disease after 1 or more lines of prior salvage chemotherapy and any FAB-AML, or
- Diagnosis of AML and age ≥ 60 and not a candidate for cytotoxic chemotherapy and any FAB-AML except FAB-M3.
- Performance status ≤ 2.
- Age ≥ 18 years.
Who cannot join
- Peripheral white blood cell count (WBC) > 10,000/microliter.
- Total bilirubin > 1.5 x normal.
- AST/ALT > 2.5 x normal.
- Serum creatinine > 2 x normal.
- Fasting serum triglyceride > 1,000 mg/dL.
- Active or poorly controlled graft vs host disease (GVHD).
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- Pregnant or nursing.
- Known CNS leukemia.
- History of positive HIV serology.
- History of positive Hepatitis C serology.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Chemotherapy within 21 days of enrollment.
- Radiation therapy within 14 days of enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase I Dose Escalation Study of Intravenous Decitabine in Combination With Oral Bexarotene in Patients With Acute Myeloid Leukemia (AML)
The main objective is to determine the safety and tolerability of combination decitabine and bexarotene during four cycles of therapy.
Read the detailed description
The investigators are seeking to study the combination of decitabine and bexarotene. These two agents have each shown efficacy in decreasing leukemic blast counts and restoring normal hematopoiesis via different mechanisms of action and with non-overlapping side-effect profiles. By combining these agents, the investigators hope to improve overall response rates. The investigators further hope to improve platelet and neutrophil counts in an even greater number of patients, thus treating two of the most important sources of morbidity and mortality in this patient population.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- Decitabine, Bexarotene
- Medical subject headings
- 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 Dacogen®
BexaroteneDrug
Also called Targretin®
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 1 | Experimental | Decitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days.
Bexarotene 100 mg/m2 PO daily for each 28 day cycle. Receives: Drug: Decitabine; Drug: Bexarotene |
| Dose Level 2 | Experimental | Decitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days.
Bexarotene 200 mg/m2 PO daily for each 28 day cycle. Receives: Drug: Decitabine; Drug: Bexarotene |
| Dose Level 3 | Experimental | Decitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days.
Bexarotene 300 mg/m2 PO daily for each 28 day cycle. Receives: Drug: Decitabine; Drug: Bexarotene |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity of combination decitabine and bexarotene during four cycles of therapy
Measured: After 4 cycles of therapy
Secondary outcomes (6)
To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy.
Measured: After 4 cycles of therapy
To determine the rates of hematological improvement, transfusion independence, time to progression, cytogenetic response, and survival.
Measured: Every 2 months for 2 years after first dose of study drug
To perform correlative studies defining transcriptional response to bexarotene in primary AML bone marrow cells.
Measured: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
To perform correlative studies examining the clonality of morphologically differentiated neutrophils by fluorescence in situ hybridization (FISH) in patients with improved neutrophil counts.
Measured: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
To perform correlative studies comparing the self-renewal of morphologically differentiated neutrophils and leukemic blasts by colony forming assays in patients with improved neutrophil counts.
Measured: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
To perform correlative studies of platelet function by PFA100 in patients with platelet counts improved to >100,000/microliter
Measured: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2009 (estimated)
- Study startMay 2010
- Primary completionMay 2013
- Study completionMay 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amanda Cashen, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01001143
- Sponsor's protocol ID
- 09-1661 / 201012801
- Acronym
- AML
- Status last verified
- Jul 2014
- First submitted
- 19 Oct 2009
- Last updated
- 29 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Dose Escalation Study of Intravenous Decitabine in Combination With Oral Bexarotene in Patients With Acute Myeloid Leukemia (AML)
- ClinicalTrials.gov ID
- NCT01001143
- Acronym / sponsor ID
- AML / 09-1661 / 201012801
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- May 2010
- Primary completion
- May 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 23 Oct 2009 (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.
The main objective is to determine the safety and tolerability of combination decitabine and bexarotene during four cycles of therapy.
Detailed description
The investigators are seeking to study the combination of decitabine and bexarotene. These two agents have each shown efficacy in decreasing leukemic blast counts and restoring normal hematopoiesis via different mechanisms of action and with non-overlapping side-effect profiles. By combining these agents, the investigators hope to improve overall response rates. The investigators further hope to improve platelet and neutrophil counts in an even greater number of patients, thus treating two of the most important sources of morbidity and mortality in this patient population.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 1 | Experimental | Drug: Decitabine, Drug: BexaroteneDecitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days. Bexarotene 100 mg/m2 PO daily for each 28 day cycle. |
| Dose Level 2 | Experimental | Drug: Decitabine, Drug: BexaroteneDecitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days. Bexarotene 200 mg/m2 PO daily for each 28 day cycle. |
| Dose Level 3 | Experimental | Drug: Decitabine, Drug: BexaroteneDecitabine 20 mg/m2 IV days 3-7 of cycle 1 and days 1-5 of subsequent cycles. Each cycle is 28 days. Bexarotene 300 mg/m2 PO daily for each 28 day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- AML with bone marrow blasts ≥ 20%.
- Relapsed disease after 1 or more lines of prior salvage chemotherapy and any FAB-AML, or
- Diagnosis of AML and age ≥ 60 and not a candidate for cytotoxic chemotherapy and any FAB-AML except FAB-M3.
- Performance status ≤ 2.
- Age ≥ 18 years.
Key exclusion criteria (13 listed)
- Peripheral white blood cell count (WBC) > 10,000/microliter.
- Total bilirubin > 1.5 x normal.
- AST/ALT > 2.5 x normal.
- Serum creatinine > 2 x normal.
- Fasting serum triglyceride > 1,000 mg/dL.
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: Dacogen® | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
| BexaroteneAlso: Targretin® | Drug | Dose Level 1, Dose Level 2, Dose Level 3 |
Primary outcome
Toxicity of combination decitabine and bexarotene during four cycles of therapy
Time frame: After 4 cycles of therapy
6 secondary outcomes
To determine the complete remission (CR) and partial remission (PR) rate after four cycles of therapy.
Time frame: After 4 cycles of therapy
To determine the rates of hematological improvement, transfusion independence, time to progression, cytogenetic response, and survival.
Time frame: Every 2 months for 2 years after first dose of study drug
To perform correlative studies defining transcriptional response to bexarotene in primary AML bone marrow cells.
Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
To perform correlative studies examining the clonality of morphologically differentiated neutrophils by fluorescence in situ hybridization (FISH) in patients with improved neutrophil counts.
Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
To perform correlative studies comparing the self-renewal of morphologically differentiated neutrophils and leukemic blasts by colony forming assays in patients with improved neutrophil counts.
Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
To perform correlative studies of platelet function by PFA100 in patients with platelet counts improved to >100,000/microliter
Time frame: Baseline, C1D3, Day 25 of even cycles, and End of Study treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2014.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
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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.
Amanda Cashen, M.D. principal investigator
Washington University School of Medicine
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 and Bexarotene in people with Leukemia, Myeloid, Acute, run by Washington University School of Medicine 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 5 inclusion and 13 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 29 Jul 2014. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Toxicity of combination decitabine and bexarotene during four cycles of therapy (time frame: After 4 cycles of therapy). 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 29 Jul 2014.