Ignite Creation Date:
2024-05-05 @ 11:34 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00081822
Status:
COMPLETED
Last Update Posted:
2012-04-20
First Post:
2004-04-21
Brief Title:
Study of Clofarabine Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia
Sponsor:
University of Alabama at Birmingham
Organization:
University of Alabama at Birmingham
Study Overview
Official Title:
A Phase I Study of Clofarabine Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia
Status:
COMPLETED
Status Verified Date:
2012-04
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:
The purpose of this study is to determine the recommended phase II dose of clofarabine when administered in combination with standard dose Ara-C to older 60 years of age patients with newly diagnosed acute myeloid leukemia AML
Detailed Description:
This phase III trial will include an initial dose escalation of clofarabine with a fixed standard dose of Ara-C in phase I to determine the optimal phase II dose Patients will be enrolled into phase I in cohorts of 3-6 beginning at Dose Level I of clofarabine 30 mgm2day days 2-6 If 03 or 16 patients experience dose-limiting toxicity DLT clofarabine will be escalated to Dose Level II 40mgm2day days 2-6 If 13 or 26 patients experience DLT on Dose Level II then Dose Level I will be declared the optimal phase II dose However if 03 or 16 patients experience DLT on Dose Level II then Dose Level II will be declared the optimal phase II dose In the event that 2 patients experience DLT at Dose Level I clofarabine will be dose reduced to Dose Level -I 225mgm2day days 2-6 Accrual will continue in cohorts of 3-6 patients in a phase I fashion If 03 or 16 patients experience DLT then Dose Level -I will be declared the optimal phase II dose In the event that 2 patients experience DLT at Dose Level -I clofarabine will be further dose reduced to Dose Level -II 15mgm2day days 2-6 Accrual will again proceed in cohorts of 3-6 patients If 03 or 16 experience DLT then Dose Level -II will be declared the optimal phase II dose In the event that 2 patients experience DLT at Dose Level -II accrual to the protocol will be halted
Enrollment will proceed at the optimal phase II dose in a Simon 2-stage design to determine the CR rate and treatment-related mortality initially in 16 patients if the CR rate and TRM is acceptable then enrollment will continue to approximately 46 patients or until complete
Induction Therapy cycle 1
7 day cycle Day 1 Aggressive Hydration x12-24hrs followed by Ara-C 100mgm2day by 24hr IV continuous infusion days 1-7
PK analysis Ara-C alone on Day 1 plasma intracellular Day 2 Dexamethasone 10mg IV QD prior to clofarabine days 2-6 Clofarabine 2 hour daily infusion days 2-6
PK analysis of Ara-C clofarabine on Day 2
Bone Marrow Apoptosis analysis plasma intracellular Day 3 Bone Marrow Apoptosis analysis plasma intracellular Day 6 PK analysis of Ara-C and clofarabine plasma only UAB only Day 8 Initiation of prophylactic antibiotic antifungal antiviral therapy Day 15 QOL analysis Day 15-22 Restaging BM Re-Induction if appropriate see below Day 16 GM-CSF 250μgm2 daily until ANC 1500μl if D15 BM aplasia no residual AML Day 28-49 Outcome BM assessment of response Re-Induction PR or Post-Remission therapy CR
QOL analysis 2 weeks after hospital discharge approximately Day 42
Re-Induction cycle 2 if appropriate if Partial Remission after Induction day 15-49 5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mgm2day days 1-5 begin 4 hours after end of clofarabine infusion Day 7 GM-CSF 250μgm2 daily may be used until recovery ANC 1500μl Day 7 Initiation of prophylactic antibiotic antifungal antiviral therapy
Post-Remission Therapy cycles 2 3 if appropriate if Complete Remission after Induction must have ANC1000μl platelets 100μl
5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mgm2day days 1-5 begin 4 hours after end of clofarabine infusion Day 7 GM-CSF 250μgm2 daily may be used until recovery ANC 1500μl Day 7 Initiation of prophylactic antibiotic antifungal antiviral therapy
Follow-up Monthly x 12 months 3-monthly x 2 years 4-monthly x 1 year 6-monthly x 1 year Annually thereafter
Enrollment will proceed at the optimal phase II dose in a Simon 2-stage design to determine the CR rate and treatment-related mortality initially in 16 patients if the CR rate and TRM is acceptable then enrollment will continue to approximately 46 patients or until complete
Induction Therapy cycle 1
7 day cycle Day 1 Aggressive Hydration x12-24hrs followed by Ara-C 100mgm2day by 24hr IV continuous infusion days 1-7
PK analysis Ara-C alone on Day 1 plasma intracellular Day 2 Dexamethasone 10mg IV QD prior to clofarabine days 2-6 Clofarabine 2 hour daily infusion days 2-6
PK analysis of Ara-C clofarabine on Day 2
Bone Marrow Apoptosis analysis plasma intracellular Day 3 Bone Marrow Apoptosis analysis plasma intracellular Day 6 PK analysis of Ara-C and clofarabine plasma only UAB only Day 8 Initiation of prophylactic antibiotic antifungal antiviral therapy Day 15 QOL analysis Day 15-22 Restaging BM Re-Induction if appropriate see below Day 16 GM-CSF 250μgm2 daily until ANC 1500μl if D15 BM aplasia no residual AML Day 28-49 Outcome BM assessment of response Re-Induction PR or Post-Remission therapy CR
QOL analysis 2 weeks after hospital discharge approximately Day 42
Re-Induction cycle 2 if appropriate if Partial Remission after Induction day 15-49 5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mgm2day days 1-5 begin 4 hours after end of clofarabine infusion Day 7 GM-CSF 250μgm2 daily may be used until recovery ANC 1500μl Day 7 Initiation of prophylactic antibiotic antifungal antiviral therapy
Post-Remission Therapy cycles 2 3 if appropriate if Complete Remission after Induction must have ANC1000μl platelets 100μl
5 day cycle Aggressive Hydration x12-24hrs Day 1 Dexamethasone 10mg IV QD days 1-5 Day 1 Clofarabine 2 hour daily infusion days 1-5 Day 1 Ara-C 100mgm2day days 1-5 begin 4 hours after end of clofarabine infusion Day 7 GM-CSF 250μgm2 daily may be used until recovery ANC 1500μl Day 7 Initiation of prophylactic antibiotic antifungal antiviral therapy
Follow-up Monthly x 12 months 3-monthly x 2 years 4-monthly x 1 year 6-monthly x 1 year Annually thereafter
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 |
|---|---|---|---|
| UAB 0341 | OTHER | Institutional study protocol number | None |