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A Phase I Study of G3139 ( NSC # 683428) in Combination With Cytarabine and Daunorubicin in Previously Untreated Patients With Acute Myeloid Leukemia (AML)>= 60 Years of Age


Phase 1
60 Years
N/A
Not Enrolling
Both
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), Secondary Acute Myeloid Leukemia, Untreated Adult Acute Myeloid Leukemia

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Trial Information

A Phase I Study of G3139 ( NSC # 683428) in Combination With Cytarabine and Daunorubicin in Previously Untreated Patients With Acute Myeloid Leukemia (AML)>= 60 Years of Age


OBJECTIVES:

I. Determine the maximum tolerated dose of daunorubicin in combination with cytarabine and
oblimersen in older patients with previously untreated acute myeloid leukemia.

II. Determine the qualitative and quantitative toxic effects of this regimen in these
patients.

III. Determine the pharmacokinetics of oblimersen in this regimen in these patients.

IV. Determine the disease-free survival and overall survival of patients treated with this
regimen.

V. Assess the spontaneous rate of apoptosis in leukemic blasts in patients before and after
initiation of treatment with oblimersen.

VI. Determine therapeutic response (complete remission) in patients treated with this
regimen.

OUTLINE: This is a dose-escalation study of daunorubicin. Patients are stratified according
to disease status (primary vs secondary).

INDUCTION THERAPY: Patients receive oblimersen (G3139) IV continuously on days 1-10 and
cytarabine IV continuously on days 4-10. Patients also receive daunorubicin IV daily on days
4-6.

Patients with bone marrow cellularity of at least 20% and at least 5% leukemic blasts at day
17 or evidence of refractory disease receive a second induction comprising G3139 IV
continuously on days 1-8, cytarabine IV continuously on days 4-8, and daunorubicin IV on
days 4-5.

CONSOLIDATION THERAPY: Beginning no sooner than 14 days after hematologic recovery from
induction therapy, patients receive G3139 IV continuously on days 1-8 and cytarabine IV over
4 hours on days 4-8. Patients receive a second course of consolidation therapy no sooner
than 14 days after hematologic recovery from the first course.

Cohorts of 3-6 patients receive escalating doses of daunorubicin until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.

Patients are followed every 2 months for 2 years.


Inclusion Criteria:



- Histologically confirmed primary or secondary acute myeloid leukemia (AML)

- More than 20% bone marrow blasts

- Myelodysplastic syndromes (MDS) or a chronic myeloproliferative disorder
antecedent to AML allowed

- Therapy-related AML allowed

- No acute promyelocytic leukemia

- At least 4 weeks

- Bilirubin no greater than 2 mg/dL

- ALT and AST no greater than 2 times upper limit of normal (unless directly
attributable to AML)

- Creatinine no greater than 2.5 mg/dL

- Ejection fraction at least 50% by MUGA or echocardiogram

- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia

- No allergy to any of the study medications

- No other uncontrolled concurrent illness

- No serious medical or psychiatric illness that would preclude giving informed consent

- Not pregnant or nursing

- Fertile patients must use effective contraception

- No prior therapy for primary AML except emergency leukapheresis

- No prior anthracyclines

- No prior chemotherapy for primary AML except hydroxyurea for hyperleukocytosis

- At least 3 months since prior chemotherapy for MDS or chronic myeloproliferative
disorders antecedent to AML

- No other concurrent chemotherapy

- No concurrent corticosteroids as anti-emetics

- No concurrent steroids except for adrenal failure or septic shock

- No concurrent hormonal therapy except hormones for non-disease-related conditions
(e.g., insulin for diabetes, tamoxifen or equivalent for breast cancer prevention or
adjuvant treatment, or estrogens or progestins for gynecologic indications)

- No prior radiotherapy for primary AML except cranial radiotherapy for CNS
leukostasis

- No concurrent palliative radiotherapy

- No concurrent whole brain radiotherapy

- No other concurrent investigational or commercial agents or therapies

- No concurrent cyclooxygenase-2 inhibitors

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

MTD of cytarabine and daunorubicin in combination with G3139, defined as the dose level just below the dose level at which DLT is observed in 2 patients, graded according to NCI CTC version 2.0

Outcome Time Frame:

Up to day 10

Safety Issue:

Yes

Principal Investigator

Guido Marcucci

Investigator Role:

Principal Investigator

Investigator Affiliation:

Ohio State University

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01409

NCT ID:

NCT00039117

Start Date:

April 2002

Completion Date:

Related Keywords:

  • 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)
  • Secondary Acute Myeloid Leukemia
  • Untreated Adult Acute Myeloid Leukemia
  • Congenital Abnormalities
  • Leukemia
  • Leukemia, Myeloid, Acute
  • Leukemia, Myeloid

Name

Location

Ohio State University Medical CenterColumbus, Ohio  43210