Ignite Creation Date:
2024-05-05 @ 6:39 PM
Last Modification Date:
2024-10-26 @ 9:36 AM
Study NCT ID:
NCT00528450
Status:
TERMINATED
Last Update Posted:
2016-01-29
First Post:
2007-09-10
Brief Title:
Tretinoin and Arsenic Trioxide With or Without Idarubicin in Treating Patients With Acute Promyelocytic Leukemia
Sponsor:
Memorial Sloan Kettering Cancer Center
Organization:
Memorial Sloan Kettering Cancer Center
Study Overview
Official Title:
Phase II Study of Combined All-Trans Retinoic Acid and Arsenic Trioxide for Acute Promyelocytic Leukemia Followed by Risk-Adapted Postremission Therapy
Status:
TERMINATED
Status Verified Date:
2015-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Lack of accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 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
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 10000μL 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
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 10000μL 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CEPHALONO-MSKCC-07108 | US NIH GrantContract | None | httpsreporternihgovquickSearchP30CA008748 |
| P30CA008748 | NIH | None | None |
| MSKCC-07108 | None | None | None |