Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia
- Conditions
- Acute Myeloid Leukemia
- Interventions
- Drug: RAD001(Everolimus)
- Registration Number
- NCT00636922
- Lead Sponsor
- Bayside Health
- Brief Summary
The main goal of this study is to assess the safety and tolerability of RAD001 in combination with low-dose cytarabine in acute myeloid leukemia patients unfit for intensive chemotherapy. The secondary goals are to investigate the likely causes of drug response or failure.
- Detailed Description
A multicentre 2-stage Phase Ib/II trial of 5-Azacitidine combined with Everolimus for AML patients over the age of 60 or relapsed AML over the age of 18. The MTD and DLT of 5-Azacitidine (7 doses over 9 days) given monthly combined with Everolimus orally for 17 days (day 5-21) each month (1 cycle) for a minimum of 6 cycles and for at least 2 cycles beyond achievement of CR and for a maximum of 12 cycles. Everolimus maintenance therapy alone may be continued at investigator's discretion until either progressive disease or dose limiting toxicity. Groups of 3 patients will be entered at each dose level. Dose escalation/stopping rules to determine the maximum tolerated dose (MTD) are as follows:
Number in cohort experiencing DLT by day 42 Action 2/3 or 3/3 No further dose escalation. Previous level is defined as MTD 0/3 Dose escalate to next level 1/3 Expand cohort to 6 patients 1/6 or 2/6 Dose escalate to next level \>2/6 No further dose escalation. Previous level is defined as MTD
Note that if dose escalation is still indicated at the highest dose level, then the MTD is at or above the last dose level. If the trial stops at the first dose, then the MTD is below the first dose level. In either of the above cases, the MTD is not determined from the trial.
Once the maximum dose level has been identified, a dose expansion phase will continue recruiting patients at the MTD until a total of 40 patients for the entire study is accrued.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 40
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Everolimus with 5-azacitidine RAD001(Everolimus) Everolimus increasing oral doses days 5-21 each cycle 5-azacitidine 75mg sub cutaneously 7 doses in 21 days
- Primary Outcome Measures
Name Time Method safety & tolerability over 24 cycles of treatment haematological toxicities (marrow status, neutrophil recovery), non-haematological grade 4 toxicity
- Secondary Outcome Measures
Name Time Method clinical Response up to 3 years measure disease free survival up to 3 years
biomarkers of response over length of treatment up to 24 cycles measure examples of biomarkers of disease response such as gene-specific methylation and phosphorylation status of mTOR targets
patient related outcomes during treatment and in followup for up to 3 years Quality of life questionnaires and treatment related toxicities
Trial Locations
- Locations (1)
BaysideHealth, The Alfred Hospital
🇦🇺Melbourne, Victoria, Australia