Ignite Creation Date:
2024-05-05 @ 5:36 PM
Last Modification Date:
2024-10-26 @ 9:34 AM
Study NCT ID:
NCT00492856
Status:
COMPLETED
Last Update Posted:
2023-01-10
First Post:
2007-06-25
Brief Title:
S0521 Combination Chemotherapy With or Without Gemtuzumab Followed By Tretinoin Mercaptopurine and Methotrexate or Observation in Treating Patients With Acute Promyelocytic Leukemia
Sponsor:
SWOG Cancer Research Network
Organization:
SWOG Cancer Research Network
Study Overview
Official Title:
S0521 A Randomized Trial of Maintenance Versus Observation for Patients With Previously Untreated Low and Intermediate Risk Acute Promyelocytic Leukemia APL Phase III
Status:
COMPLETED
Status Verified Date:
2022-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Drugs used in chemotherapy work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing Monoclonal antibodies such as gemtuzumab can block cancer growth in different ways Some block the ability of cancer cells to grow and spread Others find cancer cells and help kill them or carry cancer-killing substances to them Sometimes the cancer may not need more treatment until it progresses In this case observation may be sufficient It is not yet known whether combination chemotherapy is more effective than observation when given as maintenance therapy in treating acute promyelocytic leukemia
PURPOSE This randomized phase III trial is studying tretinoin mercaptopurine and methotrexate to see how well they work when given as maintenance therapy compared with observation after combination chemotherapy in treating patients with acute promyelocytic leukemia Randomization and observation group closed as of 81510
PURPOSE This randomized phase III trial is studying tretinoin mercaptopurine and methotrexate to see how well they work when given as maintenance therapy compared with observation after combination chemotherapy in treating patients with acute promyelocytic leukemia Randomization and observation group closed as of 81510
Detailed Description:
OBJECTIVES
Compare disease-free survival DFS among patients with previously untreated low and intermediate risk acute promyelocytic leukemia APL who are PCR-negative for Promyelocytic-retinoic acid receptor alpha PML-RARα after consolidation therapy and receive maintenance therapy versus patients who receive no maintenance therapy Randomization and observation arm closed as of 81510
Assess the toxicity of induction consolidation and maintenance in these patients
Test whether gene expression profiles assessed prior to treatment are predictive of resistance to remission induction chemotherapy and correlate with detectable minimal residual disease post-consolidation therapy Only one patient was not in molecular remission after receiving consolidation Therefore the predictive value of pre-treatment gene expression profiling could not be determined and is not reported here
Investigate in a preliminarily manner the outcomes of patients who fail to achieve or maintain PCR-negative PML-RARα fusion gene after consolidation therapy when treated with gemtuzumab ozogamicin Only one patient was treated with gemtuzumab ozogamicin as part of protocol treatment Therefore results for this objective are not reported
OUTLINE This is a randomized multicenter study
Induction therapy Patients receive oral tretinoin twice daily until morphologic complete remission CR or for a maximum of 90 days in the absence of disease progression or unacceptable toxicity Patients also receive cytarabine IV continuously on days 3-9 and daunorubicin hydrochloride IV on days 3-6
Consolidation therapy Patients who achieve CR CR with incomplete blood count recovery CRi or partial remission PR after induction therapy receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks After a 2-week rest period patients receive a second course of arsenic trioxide Within 14-30 days after blood count recovery patients receive oral tretinoin twice daily on days 1-7 and daunorubicin hydrochloride IV on days 1-3 Patients receive a second course of tretinoin and daunorubicin hydrochloride after adequate blood count recovery
Post-consolidation therapy Patients who do not achieve molecular CR CRm but do achieve CR or CRi and are still PML-RARα-positive after consolidation therapy receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15 Treatment repeats every 14 days for up to 6 courses or until PML-RARα-negative by PCR closed as of 81510Patients are stratified according to age 18 to 60 years vs 60 years acute promyelocytic leukemia APL risk group low vs intermediate and if the patient received consolidation therapy courses 3 or 4 yes vs no regardless of their CRm response These patients are randomized to 1 of 2 treatment arms Randomization and observation arm closed as of 81510 All patients are non-randomly assigned to receive post-consolidation therapy
Arm I Beginning 14-30 days after blood count recovery patients receive oral tretinoin twice daily on days 1-7 oral mercaptopurine once daily on days 1-14 and oral methotrexate on day 1 Treatment repeats every 2 weeks for up to 1 year
Arm II Patients receive no further chemotherapy Patients are followed every 3 months for 1 year Randomization and observation arm closed as of 81510 Patients undergo blood collection periodically for cytogenetic studies Samples are analyzed for PML-RARα fusion gene via reverse transcriptase-polymerase chain reaction RT-PCR assay and gene expression profiling
After completion of study treatment patients are followed every 3 months for 1 year every 6 months for 1 year and then annually for 3 years
Compare disease-free survival DFS among patients with previously untreated low and intermediate risk acute promyelocytic leukemia APL who are PCR-negative for Promyelocytic-retinoic acid receptor alpha PML-RARα after consolidation therapy and receive maintenance therapy versus patients who receive no maintenance therapy Randomization and observation arm closed as of 81510
Assess the toxicity of induction consolidation and maintenance in these patients
Test whether gene expression profiles assessed prior to treatment are predictive of resistance to remission induction chemotherapy and correlate with detectable minimal residual disease post-consolidation therapy Only one patient was not in molecular remission after receiving consolidation Therefore the predictive value of pre-treatment gene expression profiling could not be determined and is not reported here
Investigate in a preliminarily manner the outcomes of patients who fail to achieve or maintain PCR-negative PML-RARα fusion gene after consolidation therapy when treated with gemtuzumab ozogamicin Only one patient was treated with gemtuzumab ozogamicin as part of protocol treatment Therefore results for this objective are not reported
OUTLINE This is a randomized multicenter study
Induction therapy Patients receive oral tretinoin twice daily until morphologic complete remission CR or for a maximum of 90 days in the absence of disease progression or unacceptable toxicity Patients also receive cytarabine IV continuously on days 3-9 and daunorubicin hydrochloride IV on days 3-6
Consolidation therapy Patients who achieve CR CR with incomplete blood count recovery CRi or partial remission PR after induction therapy receive arsenic trioxide IV over 2 hours 5 days a week for 5 weeks After a 2-week rest period patients receive a second course of arsenic trioxide Within 14-30 days after blood count recovery patients receive oral tretinoin twice daily on days 1-7 and daunorubicin hydrochloride IV on days 1-3 Patients receive a second course of tretinoin and daunorubicin hydrochloride after adequate blood count recovery
Post-consolidation therapy Patients who do not achieve molecular CR CRm but do achieve CR or CRi and are still PML-RARα-positive after consolidation therapy receive gemtuzumab ozogamicin IV over 2 hours on days 1 and 15 Treatment repeats every 14 days for up to 6 courses or until PML-RARα-negative by PCR closed as of 81510Patients are stratified according to age 18 to 60 years vs 60 years acute promyelocytic leukemia APL risk group low vs intermediate and if the patient received consolidation therapy courses 3 or 4 yes vs no regardless of their CRm response These patients are randomized to 1 of 2 treatment arms Randomization and observation arm closed as of 81510 All patients are non-randomly assigned to receive post-consolidation therapy
Arm I Beginning 14-30 days after blood count recovery patients receive oral tretinoin twice daily on days 1-7 oral mercaptopurine once daily on days 1-14 and oral methotrexate on day 1 Treatment repeats every 2 weeks for up to 1 year
Arm II Patients receive no further chemotherapy Patients are followed every 3 months for 1 year Randomization and observation arm closed as of 81510 Patients undergo blood collection periodically for cytogenetic studies Samples are analyzed for PML-RARα fusion gene via reverse transcriptase-polymerase chain reaction RT-PCR assay and gene expression profiling
After completion of study treatment patients are followed every 3 months for 1 year every 6 months for 1 year and then annually for 3 years
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 |
|---|---|---|---|
| U10CA032102 | NIH | SWOG | httpsreporternihgovquickSearchU10CA032102 |
| S0521 | OTHER | None | None |