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

NCT00039117 | Completed Phase 1

• 5 other identifiers: NCI-2012-01409OSU-0164NCI-4630CDR0000069353U01CA076576
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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

Secondary Outcomes (6)

• 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

• Level of bcl-2 in circulating and/or marrow leukemic blasts before and after initiation of treatment with G3139

  Up to 18 weeks

• Spontaneous rate of apoptosis in leukemic blasts before and after initiation of treatment with G3139

  Up to 18 weeks

• Incidence of therapeutic response (complete remission [CR])

  Up to 2 years

• Disease-free survival

  Up to 2 years

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Biological: oblimersen sodium; Drug: cytarabine; Drug: daunorubicin hydrochloride; Other: laboratory biomarker analysis; Other: pharmacological study

Interventions

oblimersen sodium BIOLOGICAL

Given IV

Also known as: augmerosen, G3139, G3139 bcl-2 antisense oligodeoxynucleotide, Genasense

Arm I

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm I

daunorubicin hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin, RP-13057

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Ohio State University Medical Center

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Congenital Abnormalities

Interventions

oblimersen; Cytarabine; Daunorubicin

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Guido Marcucci

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2002
• First Posted: January 27, 2003
• Study Start: April 1, 2002
• Primary Completion: September 1, 2003
• Last Updated: December 4, 2015

Record last verified: 2013-06

Locations

US (1)