LeukemiaPhase 2NCT00528450
Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia
A Phase 2 study testing arsenic trioxide, idarubicin and tretinoin in people with Leukemia, run by Memorial Sloan Kettering Cancer Center at 1 site in United States.
Trial summary
RATIONALE: Tretinoin may help cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as arsenic trioxide and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Leukemia
- What is being tested?
- arsenic trioxide, idarubicin and tretinoin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2007to Jan 2011
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Morphologic diagnosis of acute promyelocytic leukemia (APL), confirmed by one of the following:
- Demonstration of t(15;17) using conventional cytogenetics or fluorescence in situ hybridization (FISH)
- Positive PML-RARα transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) assay
- Patients with CNS involvement by APL are eligible
PATIENT CHARACTERISTICS:
- Karnofsky performance status 60-100%
- Creatinine ≤ 2.0 mg/dL or creatinine clearance > 60 mL/min
- Bilirubin < 2.0 mg/dL (unless attributed to Gilbert disease)
- Alkaline phosphatase ≤ 2.5 times the upper limit of normal (ULN)
- AST and ALT ≤ 2.5 ULN
- LVEF ≥ 50% on echocardiogram or MUGA scan
- QTc ≤ 500 msec on baseline ECG
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for ≥ 4 months after the completion of study treatment
- No active serious infections not controlled by antibiotics
- No other concurrent active malignancy requiring immediate therapy
- No clinically significant cardiac disease (New York Heart Association class III or IV heart disease), including chronic arrhythmias
- No pulmonary disease
- No other serious or life-threatening condition deemed unacceptable by the principal investigator
PRIOR CONCURRENT THERAPY:
- No prior treatment for APL
Trial locations and contacts
1 site in 1 country.
United States1 site
Memorial Sloan-Kettering Cancer Center
New York, New York, 10021
About this study
Official title: Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
RATIONALE: Tretinoin may help cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as arsenic trioxide and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tretinoin together with arsenic trioxide with or without idarubicin may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving tretinoin together with arsenic trioxide with or without idarubicin works in treating patients with acute promyelocytic leukemia.
Read the detailed description
OBJECTIVES:
Primary
- To determine the rate of molecular remission after induction therapy comprising tretinoin (ATRA) and arsenic trioxide (ATO) (along with idarubicin in patients with leukocytosis) in patients with acute promyelocytic leukemia (APL).
Secondary
- To determine the rate of clinical complete remission and the time to remission after induction therapy.
- To determine the proportion of patients in molecular remission after each course of postremission therapy and to use these findings to direct the number of consolidation courses with ATRA and idarubicin that are administered.
- To determine the disease-free survival and overall survival of patients treated with this regimen.
- To determine the toxicity of this treatment regimen, including the number and length of hospitalizations, the incidence of secondary myelodysplastic syndromes or acute myeloid leukemia, and the effects of treatment on LVEF.
- To characterize the differentiation of APL cells during treatment with combined ATRA and ATO using serial immunophenotyping studies of peripheral blood and bone marrow.
- To compare the results of quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays performed on bone marrow and peripheral blood.
OUTLINE:
- Induction therapy: Patients receive tretinoin orally twice daily and arsenic trioxide IV over 1-4 hours once daily until a marrow remission is documented or for 60 days, whichever comes first. Patients with leukocytosis (WBC > 10,000/μL) also receive idarubicin IV over 10-15 minutes beginning on day 2 and continuing every other day for 4 doses. Patients who achieve a clinical complete remission (CR) proceed to consolidation therapy. If a marrow remission is not achieved after 60 days, the patient is removed from the study.
- Consolidation therapy:
- Consolidation courses 1, 2, and 3: Beginning 3-6 weeks after documentation of clinical CR, patients receive consolidation therapy comprising tretinoin orally twice daily for 15 days and arsenic trioxide IV over 1-4 hours once daily 5 days a week for 5 weeks. Consolidation therapy repeats every 3-6 weeks for 3 courses.
Patients who have a negative PML-RARα transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) assay after consolidation course 2 proceed to maintenance therapy after receiving consolidation course 3. Patients who have a negative PML-RARα transcript by RT-PCR assay after consolidation course 3, proceed to consolidation course 4 followed by maintenance therapy. Patients who have a positive PML-RARα transcript by RT-PCR assay after consolidation courses 2 and 3 proceed to consolidation courses 4 and 5.
- Consolidation course 4: Beginning 3-6 weeks after completion of consolidation course 3, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 4 days.
- Consolidation course 5: Beginning 3-6 weeks after completion of consolidation course 4, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 3 days.
Patients who remain positive for the PML-RARα transcript after 5 courses of consolidation therapy are removed from the study. Patients who have a negative PML-RARα transcript after 5 courses of consolidation therapy proceed to maintenance therapy.
- Maintenance therapy: Beginning approximately 3 months after completion of the final consolidation course, patients receive tretinoin orally twice daily for 15 days. Treatment repeats every 3 months for up to 2 years.
Disease status will be monitored with serial analyses of bone marrow and peripheral blood samples using RT-PCR for PML-RARα mRNA. Patients will be followed until relapse, death, loss to follow-up, or removal from study.
- Conditions
- Leukemia
- Being tested
- arsenic trioxide, idarubicin, tretinoin
- Keywords
- adult acute promyelocytic leukemia (M3), adult acute myeloid leukemia with t(15;17)(q22;q12), untreated adult acute myeloid leukemia
- Medical subject headings
- Leukemia, Leukemia, Promyelocytic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
arsenic trioxideDrug
idarubicinDrug
tretinoinDrug
| Study group | Role | What they receive |
|---|---|---|
| Tretinoin and Arsenic Trioxide With or Without Idarubicin | Experimental | See Outline for details Receives: Drug: arsenic trioxide; Drug: idarubicin; Drug: tretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Molecular Remission Rate
# of patients with Complete Remission
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionJan 2011
- Study completionJan 2011
Why it stopped: Lack of accrual
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 LeukemiaStudies of the same condition, open and under way.
- More trials run by Memorial Sloan Kettering 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cephalon
- Responsible party
- Sponsor
- Investigators
- Joseph G. Jurcic, MD, Principal investigator, Memorial Sloan Kettering Cancer CenterPeter Maslak, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00528450
- Sponsor's protocol ID
- 07-108
- Other IDs
- P30CA008748, MSKCC-07108, CEPHALONO-MSKCC-07108
- Status last verified
- Dec 2015
- First submitted
- 10 Sep 2007
- Last updated
- 29 Jan 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
- ClinicalTrials.gov ID
- NCT00528450
- Acronym / sponsor ID
- 07-108
- Conditions
- Leukemia
- Keywords
- adult acute promyelocytic leukemia (M3), adult acute myeloid leukemia with t(15;17)(q22;q12), untreated adult acute myeloid leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), Cephalon
- Study start
- Sep 2007
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 12 Sep 2007 (estimated)
- Results
- Posted 29 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Tretinoin may help cancer cells become more like normal cells, and to grow and spread more slowly. Drugs used in chemotherapy, such as arsenic trioxide and idarubicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving tretinoin together with arsenic trioxide with or without idarubicin may kill more cancer cells.
PURPOSE: This phase II trial is studying how well giving tretinoin together with arsenic trioxide with or without idarubicin works in treating patients with acute promyelocytic leukemia.
Detailed description
OBJECTIVES:
Primary
- To determine the rate of molecular remission after induction therapy comprising tretinoin (ATRA) and arsenic trioxide (ATO) (along with idarubicin in patients with leukocytosis) in patients with acute promyelocytic leukemia (APL).
Secondary
- To determine the rate of clinical complete remission and the time to remission after induction therapy.
- To determine the proportion of patients in molecular remission after each course of postremission therapy and to use these findings to direct the number of consolidation courses with ATRA and idarubicin that are administered.
- To determine the disease-free survival and overall survival of patients treated with this regimen.
- To determine the toxicity of this treatment regimen, including the number and length of hospitalizations, the incidence of secondary myelodysplastic syndromes or acute myeloid leukemia, and the effects of treatment on LVEF.
- To characterize the differentiation of APL cells during treatment with combined ATRA and ATO using serial immunophenotyping studies of peripheral blood and bone marrow.
- To compare the results of quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assays performed on bone marrow and peripheral blood.
OUTLINE:
- Induction therapy: Patients receive tretinoin orally twice daily and arsenic trioxide IV over 1-4 hours once daily until a marrow remission is documented or for 60 days, whichever comes first. Patients with leukocytosis (WBC > 10,000/μL) also receive idarubicin IV over 10-15 minutes beginning on day 2 and continuing every other day for 4 doses. Patients who achieve a clinical complete remission (CR) proceed to consolidation therapy. If a marrow remission is not achieved after 60 days, the patient is removed from the study.
- Consolidation therapy:
- Consolidation courses 1, 2, and 3: Beginning 3-6 weeks after documentation of clinical CR, patients receive consolidation therapy comprising tretinoin orally twice daily for 15 days and arsenic trioxide IV over 1-4 hours once daily 5 days a week for 5 weeks. Consolidation therapy repeats every 3-6 weeks for 3 courses.
Patients who have a negative PML-RARα transcript by reverse transcriptase-polymerase chain reaction (RT-PCR) assay after consolidation course 2 proceed to maintenance therapy after receiving consolidation course 3. Patients who have a negative PML-RARα transcript by RT-PCR assay after consolidation course 3, proceed to consolidation course 4 followed by maintenance therapy. Patients who have a positive PML-RARα transcript by RT-PCR assay after consolidation courses 2 and 3 proceed to consolidation courses 4 and 5.
- Consolidation course 4: Beginning 3-6 weeks after completion of consolidation course 3, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 4 days.
- Consolidation course 5: Beginning 3-6 weeks after completion of consolidation course 4, patients receive tretinoin orally twice daily for 15 days and idarubicin IV over 10-15 minutes once daily for 3 days.
Patients who remain positive for the PML-RARα transcript after 5 courses of consolidation therapy are removed from the study. Patients who have a negative PML-RARα transcript after 5 courses of consolidation therapy proceed to maintenance therapy.
- Maintenance therapy: Beginning approximately 3 months after completion of the final consolidation course, patients receive tretinoin orally twice daily for 15 days. Treatment repeats every 3 months for up to 2 years.
Disease status will be monitored with serial analyses of bone marrow and peripheral blood samples using RT-PCR for PML-RARα mRNA. Patients will be followed until relapse, death, loss to follow-up, or removal from study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tretinoin and Arsenic Trioxide With or Without Idarubicin | Experimental | Drug: arsenic trioxide, Drug: idarubicin, Drug: tretinoinSee Outline for details |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| arsenic trioxide | Drug | Tretinoin and Arsenic Trioxide With or Without Idarubicin |
| idarubicin | Drug | Tretinoin and Arsenic Trioxide With or Without Idarubicin |
| tretinoin | Drug | Tretinoin and Arsenic Trioxide With or Without Idarubicin |
Primary outcome
Molecular Remission Rate
Time frame: 2 years
# of patients with Complete Remission
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Joseph G. Jurcic, MD principal investigator
Memorial Sloan Kettering Cancer Center
Peter Maslak, MD principal investigator
Memorial Sloan Kettering 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 arsenic trioxide, idarubicin and tretinoin in people with Leukemia, run by Memorial Sloan Kettering 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?
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 29 Jan 2016. 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 29 Jan 2016). 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?
Molecular Remission Rate (time frame: 2 years). 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 Jan 2016.