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A Phase I Study Investigating the Combination of RAD001 With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)


Phase 1
61 Years
75 Years
Open (Enrolling)
Both
Leukemia

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Trial Information

A Phase I Study Investigating the Combination of RAD001 With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia (AML)


OBJECTIVES:

Primary

- To determine the maximum-tolerated dose of everolimus in combination with standard
remission-induction therapy comprising mitoxantrone hydrochloride, cytarabine, and
etoposide (MICE-regimen) followed by consolidation therapy comprising idarubicin,
cytarabine, and etoposide in older patients with newly diagnosed acute myeloid
leukemia.

Secondary

- To determine the safety profile of this regimen in these patients.

- To determine the anti-leukemic activity (complete remission rate [complete remission
and complete remission with incomplete blood count recovery]) following one or two
induction courses.

OUTLINE: This is a multicenter, dose-escalation study of everolimus.

- Standard remission-induction therapy: Patients receive mitoxantrone hydrochloride IV
over 30 minutes on days 1, 3, and 5; cytarabine IV continuously on days 1-7; etoposide
IV over 1 hour on days 1-3; and oral everolimus once a day on days 1-21. Patients with
partial remission (PR) receive a second induction course, beginning 7-17 days after
completion of induction course 1. Patients with complete remission or complete
remission with incomplete blood count recovery (CR/CRi) after induction therapy proceed
to consolidation therapy; patients who have failed to achieve PR after induction course
1 or a CR/CRi after induction course 2 are removed from study.

- Consolidation therapy: Beginning within 3 weeks from CR/CRi documentation, patients
receive idarubicin IV over 30 minutes on days 1, 3, and 5; cytarabine IV continuously
on days 1-5; etoposide IV over 1 hour on days 1-3; and oral everolimus once a day on
days 1-10. Patients may receive another course of the consolidation therapy, beginning
at least 4 weeks after initiation of consolidation therapy course 1.

After completion of study treatment, patients are followed up once a month for 1 year, every
3 months for 1 year, and then periodically thereafter.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Newly diagnosed acute myeloid leukemia (AML) (unequivocal) according to WHO
diagnostic criteria (at least 20% blasts in the bone marrow), with FAB classification
other than M3 (acute promyelocytic leukemia), and documented by bone marrow
aspiration (or biopsy in case of dry tap)

- Previously untreated primary or secondary AML (including AML following antecedent
myelodysplasia)

- No blast transformation of chronic myeloid leukemia or other myeloproliferative
disorders

- No active CNS leukemia

PATIENT CHARACTERISTICS:

- WHO performance status 0-2

- Total serum bilirubin < 2 times upper limit of normal (ULN)

- Serum creatinine < 2 times ULN

- ALT/AST ≤ 3 times ULN (unless due to organ leukemic involvement)

- LVEF ≥ 50% by echocardiogram

- No other concurrent active malignancy

- No active uncontrolled infection

- No known active hepatitis B or C or HIV positivity

- No active heart disease including myocardial infarction within the past 3 months,
symptomatic coronary artery disease, cardiac arrhythmias not controlled by
medications, or uncontrolled congestive heart failure

- No medical condition that, in the opinion of the investigator, places the patient at
an unacceptably high risk for toxicities

- No other known condition (e.g., familial, sociological, or geographical) or behavior
(including drug dependence or abuse, psychological or psychiatric illness) that, in
the opinion of the investigator, would make the patient a poor candidate for the
trial

- No known hypersensitivity to everolimus, other rapamycins (e.g., sirolimus or
temsirolimus), or to its excipients

PRIOR CONCURRENT THERAPY:

- No prior standard or investigational chemotherapy for acute myeloid leukemia or
myelodysplasia (including everolimus or other mTOR inhibitors)

- Prior hydroxyurea allowed (up to a maximum of 14 days) to control peripheral
blood leukemic cell counts

- No prior enrollment in this trial

- No other concurrent anti-leukemia agents, investigational agents, or biological
agents

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose of everolimus

Outcome Description:

MTD of RAD given in combination with the MICE regimen

Outcome Time Frame:

At one year from study entry

Safety Issue:

Yes

Principal Investigator

Sergio Amadori, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Azienda Ospedaliera Universitaria Policlinico Tor Vergata

Authority:

Italy: Ethics Committee

Study ID:

AML1208

NCT ID:

NCT01154439

Start Date:

October 2010

Completion Date:

November 2012

Related Keywords:

  • Leukemia
  • secondary acute myeloid leukemia
  • untreated adult acute myeloid leukemia
  • adult acute basophilic leukemia
  • adult acute eosinophilic leukemia
  • adult erythroleukemia (M6a)
  • adult pure erythroid leukemia (M6b)
  • adult acute megakaryoblastic leukemia (M7)
  • adult acute minimally differentiated myeloid leukemia (M0)
  • adult acute monoblastic leukemia (M5a)
  • adult acute monocytic leukemia (M5b)
  • adult acute myeloblastic leukemia with maturation (M2)
  • adult acute myeloblastic leukemia without maturation (M1)
  • adult acute myelomonocytic leukemia (M4)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with t(8;21)(q22;q22)
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

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