Acute Myeloid Leukemia Clinical Trial
Official title:
A Phase I Study of Clofarabine & Cytosine Arabinoside Therapy for Older Adults With Acute Myeloid Leukemia
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).
This phase I/II 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
mg/m2/day, days 2-6). If 0/3 or 1/6 patients experience dose-limiting toxicity (DLT),
clofarabine will be escalated to Dose Level II (40mg/m2/day, days 2-6). If >1/3 or ≥2/6
patients experience DLT on Dose Level II, then Dose Level I will be declared the optimal
phase II dose. However, if 0/3 or 1/6 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
(22.5mg/m2/day, days 2-6). Accrual will continue in cohorts of 3-6 patients, in a phase I
fashion. If 0/3 or 1/6 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 (15mg/m2/day, days 2-6). Accrual
will again proceed in cohorts of 3-6 patients. If 0/3 or 1/6 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 100mg/m2/day 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 250μg/m2 daily until ANC >1,500/μl (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 100mg/m2/day days 1-5 (begin 4 hours
after end of clofarabine infusion) Day 7 GM-CSF 250μg/m2 daily may be used until recovery
ANC >1,500/μl Day 7 Initiation of prophylactic antibiotic, antifungal & antiviral therapy
Post-Remission Therapy (cycles 2 & 3 if appropriate) (if Complete Remission after Induction;
must have ANC>1,000/μl , platelets >100/μl)
*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 100mg/m2/day days 1-5 (begin 4 hours
after end of clofarabine infusion) Day 7 GM-CSF 250μg/m2 daily may be used until recovery
ANC >1,500/μl 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
;
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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