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Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia

Primary Purpose

Acute Myeloid Leukemia

Status

Unknown status

Phase

Phase 1

Locations

Australia

Study Type

Interventional

Intervention

RAD001(Everolimus)

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia, Elderly, Unfit, Everolimus, RAD001

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Untreated AML patients (defined by WHO 2008 criteria) over the age of 60 or relapsed/refractory AML over the age of 18 who have received up to 2 previous lines of intensive chemotherapy

No prior failure to achieve at least a PR with Azacitidine or Everolimus
Provision of written informed consent
Secondary AML (including therapy-related) are included
Life expectancy of greater than 3 months in relation to diseases other then AML/MDS
ECOG performance status 0 - 3
Electrolyte levels (potassium, calcium (albumin-adjusted), magnesium, phosphorous) within normal limits (WNL) or easily correctable with supplements
Adequate hepatic function as defined by bilirubin ≤ 1.5 x the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN
Adequate renal function, with serum creatinine ≤ 1.5 x ULN or GFR > 30 ml/minute
Patients with no uncontrolled active infection
Hydroxyurea ceased 48 hours prior to study therapy

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

Sites / Locations

BaysideHealth, The Alfred Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Everolimus with 5-azacitidine

Arm Description

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

Outcomes

Primary Outcome Measures

safety & tolerability

haematological toxicities (marrow status, neutrophil recovery), non-haematological grade 4 toxicity

Secondary Outcome Measures

clinical Response

measure disease free survival up to 3 years

biomarkers of response

measure examples of biomarkers of disease response such as gene-specific methylation and phosphorylation status of mTOR targets

patient related outcomes

Quality of life questionnaires and treatment related toxicities

Full Information

NCT ID

NCT00636922

First Posted

March 10, 2008

Last Updated

February 12, 2013

Sponsor

Bayside Health

1. Study Identification

Unique Protocol Identification Number

NCT00636922

Brief Title

Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia

Official Title

A Phase I Dose Finding Study of Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia (AML) Unfit for Intensive Induction Chemotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

February 2013

Overall Recruitment Status

Unknown status

Study Start Date

February 2010 (undefined)

Primary Completion Date

July 2013 (Anticipated)

Study Completion Date

January 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayside Health

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia, Elderly, Unfit, Everolimus, RAD001

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Everolimus with 5-azacitidine

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

RAD001(Everolimus)

Other Intervention Name(s)

Everolimus

Intervention Description

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.

Primary Outcome Measure Information:

Title

safety & tolerability

Description

haematological toxicities (marrow status, neutrophil recovery), non-haematological grade 4 toxicity

Time Frame

over 24 cycles of treatment

Secondary Outcome Measure Information:

Title

clinical Response

Description

measure disease free survival up to 3 years

Time Frame

up to 3 years

Title

biomarkers of response

Description

measure examples of biomarkers of disease response such as gene-specific methylation and phosphorylation status of mTOR targets

Time Frame

over length of treatment up to 24 cycles

Title

patient related outcomes

Description

Quality of life questionnaires and treatment related toxicities

Time Frame

during treatment and in followup for up to 3 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Untreated AML patients (defined by WHO 2008 criteria) over the age of 60 or relapsed/refractory AML over the age of 18 who have received up to 2 previous lines of intensive chemotherapy No prior failure to achieve at least a PR with Azacitidine or Everolimus Provision of written informed consent Secondary AML (including therapy-related) are included Life expectancy of greater than 3 months in relation to diseases other then AML/MDS ECOG performance status 0 - 3 Electrolyte levels (potassium, calcium (albumin-adjusted), magnesium, phosphorous) within normal limits (WNL) or easily correctable with supplements Adequate hepatic function as defined by bilirubin ≤ 1.5 x the upper limit of normal (ULN) and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN Adequate renal function, with serum creatinine ≤ 1.5 x ULN or GFR > 30 ml/minute Patients with no uncontrolled active infection Hydroxyurea ceased 48 hours prior to study therapy 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Andrew Wei, MBBS PhD

Organizational Affiliation

Bayside Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

BaysideHealth, The Alfred Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3004

Country

Australia

12. IPD Sharing Statement

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Everolimus (RAD001) in Elderly Patients With Acute Myeloid Leukemia

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