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Arsenic Trioxide, High-Dose Cytarabine and Idarubicin Induction Therapy in Previously Untreated de Novo and Secondary Adult Acute Myeloid Leukemia Patients < 60 Years Old - A Phase I Study


Phase 1
18 Years
59 Years
Not Enrolling
Both
Leukemia

Thank you

Trial Information

Arsenic Trioxide, High-Dose Cytarabine and Idarubicin Induction Therapy in Previously Untreated de Novo and Secondary Adult Acute Myeloid Leukemia Patients < 60 Years Old - A Phase I Study


OBJECTIVES:

- Determine the maximum tolerated dose and/or biologically effective dose of arsenic
trioxide followed by high-dose cytarabine and idarubicin in patients with previously
untreated de novo or secondary acute myeloid leukemia.

OUTLINE: This is a dose-escalation study of arsenic trioxide. Patients are stratified
according to timing of accrual (before November 2002 vs since November 2002).

Patients receive arsenic trioxide IV over 1 hour on day 1 followed by high-dose cytarabine
IV over 1 hour every 12 hours on days 1-6 and idarubicin IV over 30 minutes on days 2-4
(immediately after doses 3, 5 and 7 of cytarabine). Patients also receive filgrastim (G-CSF)
subcutaneously beginning 12 hours after the last dose of chemotherapy and continuing until
blood counts recover.

Cohorts of 3-6 patients receive escalating doses of arsenic trioxide until the maximum
tolerated dose (MTD), current dose used for myelodysplastic syndromes or acute promyelocytic
leukemia, or biologically effective dose is reached. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose-limiting toxicity. The biologically
effective dose is defined as the dose at which 3 patients with constitutive STAT3 activity
have the activity negated after the first dose of arsenic trioxide.

PROJECTED ACCRUAL: A maximum of 40 patients (6 for stratum I [accrued before November 2002]
and 34 for stratum II [accrued since November 2002] will be accrued for this study within 3
years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed de novo or secondary acute myeloid leukemia with ≥ 20%
blasts AND at least 1 of the following characteristics*:

- Auer rods

- Peroxidase or sudan black positive blasts

- Chloroacetate esterase-positive or diffusely non-specific esterase-positive
blasts

- Presence of a myeloid immunophenotype by multiparameter flow cytometry,
including expression of one or more myeloid markers (CD13, CD33) on blasts NOTE:
*Megakaryocytic leukemia can be diagnosed by the detection of platelet antigens
(e.g. factor VIII, glycoprotein Ib or IIb/IIIa) using monoclonal antibodies or
the presence of ultrastructural platelet peroxidase

- No acute promyelocytic leukemia

- No Philadelphia-chromosome positive chronic myeloid leukemia

- Prior hematologic disorders, including myelodysplastic syndromes, aplastic anemia,
paroxysmal nocturnal hemoglobinuria, and myeloproliferative disorders allowed

PATIENT CHARACTERISTICS:

Age

- 18 to 59

Performance status

- Not specified

Life expectancy

- More than 4 weeks

Hematopoietic

- Not specified

Hepatic

- Bilirubin ≤ 2 times normal*

- SGOT ≤ 2 times normal*

- Alkaline phosphatase ≤ 2 times normal* NOTE: *Unless abnormalities are directly
attributable to leukemia

Renal

- Creatinine ≤ 1.5 times normal* NOTE: *Unless abnormalities are directly attributable
to leukemia

Cardiovascular

- Cardiac ejection fraction ≥ 45%*

- Absolute QT interval ≤ 460 msec with potassium > 4.0 mEq/L and magnesium > 1.8 mg/dL

- No myocardial infarction within the past 6 months

- No uncontrolled symptomatic congestive heart failure

- No angina pectoris

- No multifocal cardiac arrythmias

- No other severe cardiovascular disease NOTE: *Unless abnormalities are directly
attributable to leukemia

Other

- No serious medical or psychiatric illness that would preclude informed consent or
limit survival to < 4 weeks

- No uncontrolled diabetes mellitus

- No other concurrent active malignancy

- No known hypersensitivity to E. coli-derived drug preparations

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study
participation

PRIOR CONCURRENT THERAPY:

Biologic therapy

- Not specified

Chemotherapy

- No prior chemotherapy for acute leukemia, except hydroxyurea to control white blood
cell counts

- Prior chemotherapy for an antecedent malignancy or other medical condition
allowed

Endocrine therapy

- Not specified

Radiotherapy

- Prior radiotherapy for an antecedent malignancy or other medical condition allowed

Surgery

- Not specified

Type of Study:

Interventional

Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose and/or biologically effective dose or arsenic trioxide

Outcome Time Frame:

30 days after completion of study treatment

Safety Issue:

Yes

Principal Investigator

Meir Wetzler, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000387999

NCT ID:

NCT00093483

Start Date:

April 2002

Completion Date:

December 2009

Related Keywords:

  • 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 t(8;21)(q22;q22)
  • adult acute myeloid leukemia with t(16;16)(p13;q22)
  • adult acute myeloid leukemia with inv(16)(p13;q22)
  • adult acute myeloid leukemia with 11q23 (MLL) abnormalities
  • untreated adult acute myeloid leukemia
  • secondary acute myeloid leukemia
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263