Acute Promyelocytic LeukemiaPhase 2NCT00413166
All-trans Retinoic Acid, and Arsenic +/- Idarubicin
A Phase 2 study testing All-Trans Retinoic Acid (ATRA), Arsenic Trioxide (ATO) and Idarubicin in people with Acute Promyelocytic Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
The goal of this clinical research study is to learn if the combination of arsenic trioxide (ATO) with ATRA and possibly idarubicin is effective in treating patients with newly-diagnosed APL. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acute Promyelocytic Leukemia
- What is being tested?
- All-Trans Retinoic Acid (ATRA), Arsenic Trioxide (ATO) and Idarubicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Feb 2016
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- A diagnosis of APL based on the presence of the PML-RAR alpha fusion gene by cytogenetics, PCR, or POD test.
- Provision of written informed consent.
- Patients in whom therapy for APL was initiated on an emergent basis are eligible
Who cannot join
- First trimester of pregnancy (ATRA is teratogenic)
- Corrected QT (QTC) interval must not be greater than 480 milliseconds.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Treatment of Acute Promyelocytic Leukemia (APL) With All-Trans Retinoic Acid, and Arsenic +/- Idarubicin
The goal of this clinical research study is to learn if the combination of arsenic trioxide (ATO) with ATRA and possibly idarubicin is effective in treating patients with newly-diagnosed APL.
Read the detailed description
All-trans retinoic acid (ATRA) and ATO are designed to cause the APL cells to mature and function normally. Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells).
If you are found to be eligible to take part in this study, you will begin induction. During induction, you will receive ATRA, by mouth starting on Day 1. You will also receive ATO through a needle in your vein over 2 hours starting on Day 1. You will continue receiving the drugs every day until your bone marrow no longer shows APL cells.
If you had a high white blood cell count at screening, you will receive idarubicin through a needle in your vein over about 30 minutes one dose only on any day of Day 1 through 5.
During induction, blood (about 1-3 tablespoons) will be drawn every day during Week 1, and then 2 times a week after that. This blood will be drawn for routine tests.
During induction (about 21-28 days after beginning treatment), you will have a bone marrow aspirate to check the status of the disease. This may be performed more often if the doctor thinks it is needed.
If you achieve a complete remission during the induction phase, you will continue to the maintenance phase. During the maintenance phase, you will receive ATO by vein over 2 hours Monday-Friday for 4 weeks. After the 4 weeks of receiving the study drug, you will have a 4-week period "off" (when no study drug is given). ATRA is given by mouth every day for 2 weeks. This 2 weeks is followed by 2 additional weeks when no study drug will be given. You will continue to take ATRA until treatment with ATO is complete.
During maintenance, blood (about 1-3 tablespoons) will be drawn before every 4-week cycle of ATO, and then every week for routine tests. You will also have an ECG before every 4 week cycle when you take ATO.
If you do not achieve a complete remission during induction you will be taken off study.
If at any point during the study your white blood cell count rises above 10,000, you will receive idarubicin by vein over 30 minutes.
You will remain in the hospital for about the first 7 days of induction. After that, you must remain in Houston for the next 3-4 weeks. Once in the maintenance phase, you may be treated at home, but must return to M. D. Anderson for study visits.
After maintenance is complete, you will have follow-up visits for an additional 2 years. If at any time during the active study or follow-up the disease gets worse or intolerable side effects occur, you will be taken off the study.
If you had a low or high white blood cell count when you joined the study, you will have follow-up visits every 3 months for 2 years. At these visits, blood (about 1 tablespoon) will be drawn for routine tests and you will have a bone marrow aspirate.
This is an investigational study. Idarubicin, ATRA and ATO are FDA approved and commercially available. However, their use in this study and in this combination is considered investigational. Its use in APL patients is investigational. Up to 80 patients will take part in this multicenter study. All will be enrolled at M. D. Anderson.
- Conditions
- Acute Promyelocytic Leukemia
- Being tested
- All-Trans Retinoic Acid (ATRA), Arsenic Trioxide (ATO), Idarubicin, Gemtuzumab Ozogamicin
- Keywords
- Acute Promyelocytic Leukemia, APL, ATRA, All-Trans Retinoic Acid, Arsenic Trioxide, Theophylline, Gemtuzumab
- Medical subject headings
- Leukemia, Promyelocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
All-Trans Retinoic Acid (ATRA)Drug
Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1
Arsenic Trioxide (ATO)Drug
Induction: 0.15 mg/kg daily IV beginning day 1
IdarubicinDrug
Also called Idamycin
- 12 mg/m2 one dose only (may be given on day 1 to 5 of induction)
- If either ATRA or ATO are discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses will be administered once every 4 to 5 weeks (depending on the recovery of counts) until 28 weeks has elapsed from the Complete Recovery date.
Gemtuzumab OzogamicinDrug
Induction: 9 mg/m2 on day 1 of induction
| Study group | Role | What they receive |
|---|---|---|
| Induction ATRA + ATO + Idarubicin | Experimental | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO)
ATRA 45 mg/m2 daily by mouth beginning day 1; ATO 0.15 mg/kg by vein daily beginning on day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days starting on day 1. Receives: Drug: All-Trans Retinoic Acid (ATRA); Drug: Arsenic Trioxide (ATO); Drug: Idarubicin |
| Maintenance | Experimental | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO)
ATO 0.15 mg/kg by vein over 2 hours Monday-Friday for 4 weeks, then a 4-week break. ATRA 45 mg/m2 by mouth every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete. Receives: Drug: All-Trans Retinoic Acid (ATRA); Drug: Arsenic Trioxide (ATO); Drug: Idarubicin |
| Induction ATRA + ATO + GO | Experimental | All-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) + Gemtuzumab Ozogamicin (GO)
ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1; ATO 0.15 mg/kg IV daily beginning on day 1; GO 9 mg/m2 on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1.
Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed. Receives: Drug: All-Trans Retinoic Acid (ATRA); Drug: Arsenic Trioxide (ATO); Drug: Idarubicin; Drug: Gemtuzumab Ozogamicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete Response (CR) Rate
Response defined as CR (marrow with <5% blasts and no abnormal promyelocytes together with neutrophil count >1000 and platelet count >100,000) and toxicity as Acute promyelocytic leukemia (APL) differentiation syndrome, arrhythmia, peripheral neuropathy.
Bone marrow aspirate performed to check the status of the disease.
Measured: 1 month, up to day 85 of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionFeb 2016
- Study completionFeb 2016
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.
- Other trials for Acute Promyelocytic LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe 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
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Farhad Ravandi-Kashani, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00413166
- Sponsor's protocol ID
- 2006-0706
- Other IDs
- NCI-2012-01395
- Status last verified
- Apr 2019
- First submitted
- 15 Dec 2006
- Last updated
- 7 May 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Acute Promyelocytic Leukemia (APL) With All-Trans Retinoic Acid, and Arsenic +/- Idarubicin
- ClinicalTrials.gov ID
- NCT00413166
- Acronym / sponsor ID
- 2006-0706
- Conditions
- Acute Promyelocytic Leukemia
- Keywords
- Acute Promyelocytic Leukemia, APL, ATRA, All-Trans Retinoic Acid, Arsenic Trioxide, Theophylline, Gemtuzumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Dec 2006
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 19 Dec 2006 (estimated)
- Results
- Posted 18 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical research study is to learn if the combination of arsenic trioxide (ATO) with ATRA and possibly idarubicin is effective in treating patients with newly-diagnosed APL.
Detailed description
All-trans retinoic acid (ATRA) and ATO are designed to cause the APL cells to mature and function normally. Idarubicin is designed to cause breaks in both strands of DNA (the genetic material of cells).
If you are found to be eligible to take part in this study, you will begin induction. During induction, you will receive ATRA, by mouth starting on Day 1. You will also receive ATO through a needle in your vein over 2 hours starting on Day 1. You will continue receiving the drugs every day until your bone marrow no longer shows APL cells.
If you had a high white blood cell count at screening, you will receive idarubicin through a needle in your vein over about 30 minutes one dose only on any day of Day 1 through 5.
During induction, blood (about 1-3 tablespoons) will be drawn every day during Week 1, and then 2 times a week after that. This blood will be drawn for routine tests.
During induction (about 21-28 days after beginning treatment), you will have a bone marrow aspirate to check the status of the disease. This may be performed more often if the doctor thinks it is needed.
If you achieve a complete remission during the induction phase, you will continue to the maintenance phase. During the maintenance phase, you will receive ATO by vein over 2 hours Monday-Friday for 4 weeks. After the 4 weeks of receiving the study drug, you will have a 4-week period "off" (when no study drug is given). ATRA is given by mouth every day for 2 weeks. This 2 weeks is followed by 2 additional weeks when no study drug will be given. You will continue to take ATRA until treatment with ATO is complete.
During maintenance, blood (about 1-3 tablespoons) will be drawn before every 4-week cycle of ATO, and then every week for routine tests. You will also have an ECG before every 4 week cycle when you take ATO.
If you do not achieve a complete remission during induction you will be taken off study.
If at any point during the study your white blood cell count rises above 10,000, you will receive idarubicin by vein over 30 minutes.
You will remain in the hospital for about the first 7 days of induction. After that, you must remain in Houston for the next 3-4 weeks. Once in the maintenance phase, you may be treated at home, but must return to M. D. Anderson for study visits.
After maintenance is complete, you will have follow-up visits for an additional 2 years. If at any time during the active study or follow-up the disease gets worse or intolerable side effects occur, you will be taken off the study.
If you had a low or high white blood cell count when you joined the study, you will have follow-up visits every 3 months for 2 years. At these visits, blood (about 1 tablespoon) will be drawn for routine tests and you will have a bone marrow aspirate.
This is an investigational study. Idarubicin, ATRA and ATO are FDA approved and commercially available. However, their use in this study and in this combination is considered investigational. Its use in APL patients is investigational. Up to 80 patients will take part in this multicenter study. All will be enrolled at M. D. Anderson.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Induction ATRA + ATO + Idarubicin | Experimental | Drug: All-Trans Retinoic Acid (ATRA), Drug: Arsenic Trioxide (ATO), Drug: IdarubicinAll-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATRA 45 mg/m2 daily by mouth beginning day 1; ATO 0.15 mg/kg by vein daily beginning on day 1; Idarubicin 12 mg/m2 x 1 dose; Methylprednisolone 50 mg daily for 5 days starting on day 1. |
| Maintenance | Experimental | Drug: All-Trans Retinoic Acid (ATRA), Drug: Arsenic Trioxide (ATO), Drug: IdarubicinAll-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) ATO 0.15 mg/kg by vein over 2 hours Monday-Friday for 4 weeks, then a 4-week break. ATRA 45 mg/m2 by mouth every day for 2 weeks, followed by 2 additional weeks of no study drug. Continue ATRA until treatment with ATO complete. |
| Induction ATRA + ATO + GO | Experimental | Drug: All-Trans Retinoic Acid (ATRA), Drug: Arsenic Trioxide (ATO), Drug: Idarubicin, Drug: Gemtuzumab OzogamicinAll-Trans Retinoic Acid (ATRA) + Arsenic Trioxide (ATO) + Gemtuzumab Ozogamicin (GO) ATRA 45 mg/m2 daily po (in 2 divided doses) beginning day 1; ATO 0.15 mg/kg IV daily beginning on day 1; GO 9 mg/m2 on day 1 Methylprednisolone 50 mg daily for 5 days followed by rapid taper starting on day 1. Theophylline 100mg p.o. bid days 1-3, 200 mg p.o. bid days 4-6, and 300 mg p.o. bid thereafter during periods when patient is receiving ATRA or ATO. Theophylline administration continues until therapy with ATO and ATRA is completed. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- A diagnosis of APL based on the presence of the PML-RAR alpha fusion gene by cytogenetics, PCR, or POD test.
- Provision of written informed consent.
- Patients in whom therapy for APL was initiated on an emergent basis are eligible
Key exclusion criteria (2 listed)
- First trimester of pregnancy (ATRA is teratogenic)
- Corrected QT (QTC) interval must not be greater than 480 milliseconds.
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 |
|---|---|---|
| All-Trans Retinoic Acid (ATRA)Induction: 45 mg/m2 daily by mouth in 2 divided doses beginning day 1 | Drug | Induction ATRA + ATO + GO, Induction ATRA + ATO + Idarubicin, Maintenance |
| Arsenic Trioxide (ATO)Induction: 0.15 mg/kg daily IV beginning day 1 | Drug | Induction ATRA + ATO + GO, Induction ATRA + ATO + Idarubicin, Maintenance |
| IdarubicinAlso: Idamycin1. 12 mg/m2 one dose only (may be given on day 1 to 5 of induction) 2. If either ATRA or ATO are discontinued due to toxicity, idarubicin 12 mg/m2 x 2 doses will be administered once every 4 to 5 weeks (depending on the recovery of counts) until 28 weeks has elapsed from the Complete Recovery date. | Drug | Induction ATRA + ATO + GO, Induction ATRA + ATO + Idarubicin, Maintenance |
| Gemtuzumab OzogamicinInduction: 9 mg/m2 on day 1 of induction | Drug | Induction ATRA + ATO + GO |
Primary outcome
Complete Response (CR) Rate
Time frame: 1 month, up to day 85 of treatment
Response defined as CR (marrow with <5% blasts and no abnormal promyelocytes together with neutrophil count >1000 and platelet count >100,000) and toxicity as Acute promyelocytic leukemia (APL) differentiation syndrome, arrhythmia, peripheral neuropathy. Bone marrow aspirate performed to check the status of the disease.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 May 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas MD Anderson Cancer Center WebsiteLink 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.
Farhad Ravandi-Kashani, MD principal investigator
M.D. Anderson Cancer Center
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 All-Trans Retinoic Acid (ATRA), Arsenic Trioxide (ATO) and Idarubicin in people with Acute Promyelocytic Leukemia, run by M.D. Anderson Cancer Center 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 3 inclusion and 2 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 May 2019. 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 18 Apr 2019). 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?
Complete Response (CR) Rate (time frame: 1 month, up to day 85 of treatment). 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 7 May 2019.