Ignite Creation Date:
2024-05-05 @ 5:25 PM
Last Modification Date:
2024-10-26 @ 9:31 AM
Study NCT ID:
NCT00454480
Status:
COMPLETED
Last Update Posted:
2013-08-26
First Post:
2007-03-27
Brief Title:
Combination Chemotherapy With or Without Gemtuzumab Ozogamicin or Tipifarnib in Treating Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes
Sponsor:
The University of New South Wales
Organization:
National Cancer Institute NCI
Study Overview
Official Title:
A Programme of Treatment Development for Older Patients With Acute Myeloid Leukemia and High Risk Myelodysplastic Syndrome
Status:
COMPLETED
Status Verified Date:
2008-08
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 ozogamicin 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 Tipifarnib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth Giving combination chemotherapy together with gemtuzumab ozogamicin or tipifarnib may kill more cancer cells
PURPOSE This randomized phase IIIII trial is studying different combination chemotherapy regimens to compare how well they work when given with or without gemtuzumab ozogamicin or tipifarnib in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndromes
PURPOSE This randomized phase IIIII trial is studying different combination chemotherapy regimens to compare how well they work when given with or without gemtuzumab ozogamicin or tipifarnib in treating patients with acute myeloid leukemia or high-risk myelodysplastic syndromes
Detailed Description:
OBJECTIVES
Primary patients considered fit for intensive treatment
Compare the efficacy and toxicity of daunorubicin hydrochloride and cytarabine DA vs daunorubicin hydrochloride and clofarabine DClo as induction therapy in older patients with acute myeloid leukemia or high-risk myelodysplastic syndromes
Assess the value of gemtuzumab ozogamicin when given in combination with DA or DClo during course 1 of induction therapy
Compare a total of two vs three courses of treatment in patients who achieve at least partial remission 15 blasts after course 1 of induction therapy
Compare the use of demethylation maintenance therapy comprising azacitidine vs no maintenance therapy in these patients
Assess the value of reduced-intensity allogeneic stem cell transplantation as consolidation in patients with matched donors
Primary patients considered unfit for intensive treatment
Compare the efficacy and toxicity of low-dose cytarabine with vs without gemtuzumab ozogamicin in these patients
Compare the efficacy and toxicity of low-dose cytarabine with vs without arsenic trioxide in these patients
Compare the efficacy and toxicity of low-dose cytarabine vs low-dose clofarabine in these patients
Secondary
Evaluate the relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission
Correlate molecular detection of FLT3 and RAS mutation genetic signature and resistance protein status with response to treatment
Evaluate methods of minimal residual disease monitoring
Correlate gene methylation status with treatment with maintenance azacitidine
OUTLINE This is a randomized controlled factorial design prospective multicenter study Patients are stratified according to age 60 years vs 60-64 years vs 65-69 years vs 70-74 years vs 75 years performance status WBC count 0-99000mm³ vs 10-499000mm³ vs 50-999000mm³ vs 100000mm³ and type of disease de novo acute myeloid leukemia AML vs secondary AML vs high-risk myelodysplastic syndromes Patients receive treatment according to disease status fit for intensive treatment vs unfit for intensive treatment
Intensive treatment for patients considered fit for intensive treatment
Induction therapy Patients are randomized to 1 of 4 treatment arms
Arm I For course 1 patients receive daunorubicin hydrochloride DH IV over 1 hour on days 1 3 and 5 and cytarabine IV twice daily on days 1-10 For course 2 patients receive DH as in course 1 and cytarabine IV twice daily on days 1-8 Courses are 4 weeks in duration
Arm II Patients receive DH IV over 1 hour on days 1 3 and 5 and clofarabine IV over 1 hour on days 1-5 Treatment repeats every 4 weeks for 2 courses
Arm III For course 1 patients receive DH IV over 1 hour on days 1 3 and 5 cytarabine IV twice daily on days 1-10 and gemtuzumab ozogamicin GO IV over 2 hours on day 1 For course 2 patients receive DH as in course 1 and cytarabine IV twice daily on days 1-8 Courses are 4 weeks in duration
Arm IV For course 1 patients receive DH and clofarabine as in arm II and GO as in arm III For course 2 patients receive DH and clofarabine as in arm II Courses are 4 weeks in duration
Patients who fail to achieve partial remission PR or complete remission CR after course 1 but achieve CR after course 2 receive a third course of chemotherapy comprising DH IV over 1 hour on days 1 and 3 and cytarabine IV twice daily on day 1-5 Patients then proceed to randomization for maintenance therapy
Patients who achieve PR or CR after course 1 and are in CR after course 2 are randomized to receive or not receive a third course of chemotherapy as above Patients then proceed to randomization for maintenance therapy
Patients who have an HLA-matched donor may proceed to nonintensive allogeneic stem cell transplantation ASCT
Nonintensive ASCT Patients receive a nonintensive allograft comprising 1 of 2 mini-allograft protocols
Protocol 1 Patients receive fludarabine on days -9 to -5 busulfan on days -3 and -2 and alemtuzumab on days -5 to -1 Patients undergo ASCT on day 0
Protocol 2 Patients receive fludarabine on days -7 to -3 melphalan on day -2 and alemtuzumab on days -8 to -4 Patients undergo ASCT on day 0
Maintenance Therapy Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive azacitidine subcutaneously SC once daily on days 1-5 Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity
Arm II Patients do not receive maintenance therapy
Nonintensive treatment for patients considered unfit for intensive treatment Patients are randomized to 1 of 4 treatment arms
Arm I Patients receive low-dose cytarabine LDC SC twice daily on days 1-10
Arm II Patients receive LDC as in arm I and GO IV over 2 hours on day 1
Arm III Patients receive low-dose clofarabine IV over 1 hour once daily on days 1-5
Arm IV Patients receive LDC as in arm I and arsenic trioxide IV over 1-2 hours on days 1-5 9 and 11
Treatment in all arms repeats every 4-6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
Bone marrow is collected at diagnosis and examined for characterization of FLT3 and RAS mutations by immunophenotyping gene expression by DNA microarray and cytogenetic analysis Blood samples are collected at baseline and after 18 36 and 54 weeks of treatment for assessment of gene methylation status
After completion of study therapy patients are followed at 6 and 12 months and then annually thereafter
PROJECTED ACCRUAL A total of 2000 patients will be accrued for this study
Primary patients considered fit for intensive treatment
Compare the efficacy and toxicity of daunorubicin hydrochloride and cytarabine DA vs daunorubicin hydrochloride and clofarabine DClo as induction therapy in older patients with acute myeloid leukemia or high-risk myelodysplastic syndromes
Assess the value of gemtuzumab ozogamicin when given in combination with DA or DClo during course 1 of induction therapy
Compare a total of two vs three courses of treatment in patients who achieve at least partial remission 15 blasts after course 1 of induction therapy
Compare the use of demethylation maintenance therapy comprising azacitidine vs no maintenance therapy in these patients
Assess the value of reduced-intensity allogeneic stem cell transplantation as consolidation in patients with matched donors
Primary patients considered unfit for intensive treatment
Compare the efficacy and toxicity of low-dose cytarabine with vs without gemtuzumab ozogamicin in these patients
Compare the efficacy and toxicity of low-dose cytarabine with vs without arsenic trioxide in these patients
Compare the efficacy and toxicity of low-dose cytarabine vs low-dose clofarabine in these patients
Secondary
Evaluate the relevance of the presence of a cytogenetic abnormality in the bone marrow of patients in morphological remission
Correlate molecular detection of FLT3 and RAS mutation genetic signature and resistance protein status with response to treatment
Evaluate methods of minimal residual disease monitoring
Correlate gene methylation status with treatment with maintenance azacitidine
OUTLINE This is a randomized controlled factorial design prospective multicenter study Patients are stratified according to age 60 years vs 60-64 years vs 65-69 years vs 70-74 years vs 75 years performance status WBC count 0-99000mm³ vs 10-499000mm³ vs 50-999000mm³ vs 100000mm³ and type of disease de novo acute myeloid leukemia AML vs secondary AML vs high-risk myelodysplastic syndromes Patients receive treatment according to disease status fit for intensive treatment vs unfit for intensive treatment
Intensive treatment for patients considered fit for intensive treatment
Induction therapy Patients are randomized to 1 of 4 treatment arms
Arm I For course 1 patients receive daunorubicin hydrochloride DH IV over 1 hour on days 1 3 and 5 and cytarabine IV twice daily on days 1-10 For course 2 patients receive DH as in course 1 and cytarabine IV twice daily on days 1-8 Courses are 4 weeks in duration
Arm II Patients receive DH IV over 1 hour on days 1 3 and 5 and clofarabine IV over 1 hour on days 1-5 Treatment repeats every 4 weeks for 2 courses
Arm III For course 1 patients receive DH IV over 1 hour on days 1 3 and 5 cytarabine IV twice daily on days 1-10 and gemtuzumab ozogamicin GO IV over 2 hours on day 1 For course 2 patients receive DH as in course 1 and cytarabine IV twice daily on days 1-8 Courses are 4 weeks in duration
Arm IV For course 1 patients receive DH and clofarabine as in arm II and GO as in arm III For course 2 patients receive DH and clofarabine as in arm II Courses are 4 weeks in duration
Patients who fail to achieve partial remission PR or complete remission CR after course 1 but achieve CR after course 2 receive a third course of chemotherapy comprising DH IV over 1 hour on days 1 and 3 and cytarabine IV twice daily on day 1-5 Patients then proceed to randomization for maintenance therapy
Patients who achieve PR or CR after course 1 and are in CR after course 2 are randomized to receive or not receive a third course of chemotherapy as above Patients then proceed to randomization for maintenance therapy
Patients who have an HLA-matched donor may proceed to nonintensive allogeneic stem cell transplantation ASCT
Nonintensive ASCT Patients receive a nonintensive allograft comprising 1 of 2 mini-allograft protocols
Protocol 1 Patients receive fludarabine on days -9 to -5 busulfan on days -3 and -2 and alemtuzumab on days -5 to -1 Patients undergo ASCT on day 0
Protocol 2 Patients receive fludarabine on days -7 to -3 melphalan on day -2 and alemtuzumab on days -8 to -4 Patients undergo ASCT on day 0
Maintenance Therapy Patients are randomized to 1 of 2 treatment arms
Arm I Patients receive azacitidine subcutaneously SC once daily on days 1-5 Treatment repeats every 6 weeks for 9 courses in the absence of disease progression or unacceptable toxicity
Arm II Patients do not receive maintenance therapy
Nonintensive treatment for patients considered unfit for intensive treatment Patients are randomized to 1 of 4 treatment arms
Arm I Patients receive low-dose cytarabine LDC SC twice daily on days 1-10
Arm II Patients receive LDC as in arm I and GO IV over 2 hours on day 1
Arm III Patients receive low-dose clofarabine IV over 1 hour once daily on days 1-5
Arm IV Patients receive LDC as in arm I and arsenic trioxide IV over 1-2 hours on days 1-5 9 and 11
Treatment in all arms repeats every 4-6 weeks for 4 courses in the absence of disease progression or unacceptable toxicity
Bone marrow is collected at diagnosis and examined for characterization of FLT3 and RAS mutations by immunophenotyping gene expression by DNA microarray and cytogenetic analysis Blood samples are collected at baseline and after 18 36 and 54 weeks of treatment for assessment of gene methylation status
After completion of study therapy patients are followed at 6 and 12 months and then annually thereafter
PROJECTED ACCRUAL A total of 2000 patients will be accrued for this study
Study Oversight
Has Oversight DMC:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?:
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MREC-CU106 | None | None | None |
| EUDRACT-2005-002846-14 | None | None | None |
| UHW-AML16 | None | None | None |
| EU-20677 | None | None | None |
| ISRCTN11036523 | None | None | None |