Oblimersen, Cytarabine, and Daunorubicin in Treating Older Patients With Acute Myeloid Leukemia

Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00039117
• Other study ID #: NCI-2012-01409
• Secondary ID: OSU-0164NCI-4630
• Status: Completed
• Phase: Phase 1
• First received: June 6, 2002
• Last updated: December 3, 2015
• Start date: April 2002

Study information

• Verified date: June 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Phase I trial to study the effectiveness of combining oblimersen with cytarabine and daunorubicin in treating older patients who have previously untreated acute myeloid leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Oblimersen may help cytarabine and daunorubicin kill more cancer cells by making them more sensitive to chemotherapy.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. primary completion date: September 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• 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
• Leukemia, Myeloid, Acute
• Secondary Acute Myeloid Leukemia
• Untreated Adult Acute Myeloid Leukemia

Intervention

Biological:
• oblimersen sodium
Given IV

Drug:
• cytarabine
Given IV
• daunorubicin hydrochloride
Given IV

Other:
• laboratory biomarker analysis
Correlative studies
• pharmacological study
Correlative studies

Locations

Country	Name	City	State
United States	Ohio State University Medical Center	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Up to day 10	Yes
Primary	Incidence of adverse events, graded according to NCI CTC version 2.0	We will define the qualitative and quantitative toxicities in regard to organ specificity, time course, predictability, and reversibility.	Up to 2 years	Yes
Secondary	Pharmacokinetics of G3139		During induction therapy on day 1 at hour 0 and 24hours after G3139 administration; day 4 at hour 73 before cytarabine administration; day 11 at hour 0 and .5, 1, 2, 4, 6, and 8 hours	No
Secondary	Level of bcl-2 in circulating and/or marrow leukemic blasts before and after initiation of treatment with G3139		Up to 18 weeks	No
Secondary	Spontaneous rate of apoptosis in leukemic blasts before and after initiation of treatment with G3139		Up to 18 weeks	No
Secondary	Incidence of therapeutic response (complete remission [CR])		Up to 2 years	No
Secondary	Disease-free survival		Up to 2 years	No
Secondary	Overall survival		Up to 2 years	No