Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia

NCT ID: NCT00636922

Last Updated: 2013-02-15

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2014-01-31

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.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Everolimus with 5-azacitidine

Everolimus increasing oral doses days 5-21 each cycle 5-azacitidine 75mg sub cutaneously 7 doses in 21 days

Group Type: EXPERIMENTAL

RAD001(Everolimus)

Intervention Type: DRUG

In this study, 5-azacitidine will be administered sc for 7 doses over 9 days in a 28 day cycle. Everolimus will be administered orally with the first dose starting on day 5 (first Friday) of each cycle and continued until day 21 of each cycle. Patients will be treated with combined azacitidine + Everolimus for a minimum of 6 cycles and until at least 2 cycles after documentation of CR. Upon cessation of azacitidine, the patient will be permitted to take Everolimus maintenance therapy until progression at the investigator's discretion.

Interventions

RAD001(Everolimus)

In this study, 5-azacitidine will be administered sc for 7 doses over 9 days in a 28 day cycle. Everolimus will be administered orally with the first dose starting on day 5 (first Friday) of each cycle and continued until day 21 of each cycle. Patients will be treated with combined azacitidine + Everolimus for a minimum of 6 cycles and until at least 2 cycles after documentation of CR. Upon cessation of azacitidine, the patient will be permitted to take Everolimus maintenance therapy until progression at the investigator's discretion.

Intervention Type: DRUG

Other Intervention Names

Everolimus

Eligibility Criteria

Exclusion Criteria

• Any serious medical or psychiatric conditions which the investigator feels may interfere with the patient's ability to give informed consent or participate in the procedures or evaluations of the study
• History of major non-compliance to medication
• Evidence of CNS leukemia
• Uncontrolled viral infection with known HIV or Hepatitis type B or C
• Currently active gastrointestinal disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection), or other disease, that prevents the patient from absorbing or taking oral medication
• Any other concurrent severe and/or uncontrolled medical conditions (eg. acute or chronic liver disease, infection, pulmonary disease) that in the opinion of the investigator could potentiate unacceptable safety risks or jeopardize compliance with the protocol
• Males with a female partner of childbearing potential do not agree to use at least 2 effective contraceptive methods throughout the study and for 6 months following the date of last dose

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayside Health

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Andrew Wei, MBBS PhD

Role: PRINCIPAL_INVESTIGATOR

Bayside Health

Locations

BaysideHealth, The Alfred Hospital

Melbourne, Victoria, Australia

Countries

Australia

Other Identifiers

CRAD001C24112

Identifier Type: -

Identifier Source: org_study_id