Cytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia

NCT00513305 | Terminated Phase 3 Results

• 1 other identifier: C18477/3059/AM/US-CA
• Study Type: interventional
• Target: 67
• Locations: 2 countries
• Sites: 12

Brief Summary

The primary objective of this study is to determine whether low-dose cytarabine in combination with arsenic trioxide is more effective than low-dose cytarabine alone in achieving complete remission in elderly patients (≥60 years of age) with acute myeloid leukemia.

Conditions

Acute Myeloid Leukemia

Keywords

acute myeloid leukemia, cytarabine, arsenic trioxide.

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants in Complete Remission (CR)

  The primary efficacy variable was the percentage of subjects in each treatment group who achieved complete remission after treatment with study drug. Complete remission was defined as: 1) Less than 5% blasts in normocellular bone marrow sample. 2) No blasts in bone marrow sample containing Auer rods. 3)Clearance of previous extramedullary disease. 4)Normal values for absolute neutrophil count (at least 1000/microliter), platelet count (at least 100,000/microliter), without platelet transfusions, and in absence of peripheral myeloblasts.

  From baseline through Day 70. Assessments were performed on Day 21 in cycle 1, no later than Day 56 of cycle 1 or 2 (if applicable), and no later than Day 70 of cycle 1 or 2 (if applicable) or at any other time at the discretion of the investigator

Secondary Outcomes (5)

• Number of Participants Who Died or Were Censored by 24 Months

  From Baseline through 24 months following Baseline

• Proportion of Participants With Relapse-Free Survival (RFS)Using the Kaplan-Meier Estimate

  From Baseline (randomization) through 24 months following Baseline

• Number of Participants Who Experienced Early Death

  14 days from start of study drug treatment

• Number of Participants Who Experienced Induction (Thirty-Day) Mortality

  Up to 30 days following start of study drug treatment

• Proportion of Participants Surviving at 6 Months and 12 Months Using the Kaplan Meier Estimate

  Baseline through 12 months

Study Arms (2)

Low-dose cytarabine plus arsenic trioxide

ACTIVE COMPARATOR

Cycle 1 cytarabine 10 mg/m\^2 was administered subcutaneously (sc) twice daily (bid) on days 1-14. 0.25 mg/kg arsenic trioxide was administered intravenously (iv) on days 1-5 and days 8-12. Cycle 2 A second identical cycle of cytarabine and arsenic trioxide was given to patients with persistent disease. Patients who achieved complete remission (CR), complete remission with incomplete platelet count recovery (CRp), or partial remission (PR) after 1 or 2 cycles received a 14-day consolidation cycle of cytarabine and arsenic trioxide with the doses and schedule identical to the initial cycle. A recovery period of up to 4 weeks between the attainment of CR, CRp, or PR and the initiation of consolidation treatment was allowed. Patients who completed consolidation treatment started maintenance treatment of arsenic trioxide 0.25 mg/kg iv on days 1 and 4 and cytarabine 10 mg/m\^2 sc bid on days 1 through 7 of a 28-day cycle.

Drug: Arsenic trioxide; Drug: Low-dose cytarabine alone

Low-dose cytarabine alone

ACTIVE COMPARATOR

Cytarabine was administered at a dose of 10 mg/m\^2 sc bid from days 1-14 of cycle 1. A second identical cycle of cytarabine was given to patients with persistent disease. Patients who achieved a complete remission (CR), complete remission with incomplete platelet count recovery (CRp), or partial remission (PR) after 1 or 2 cycles received a 14-day consolidation cycle of cytarabine with the doses and schedule identical to the initial treatment cycle. Recovery period up to 4 weeks between the attainment of CR, CRp, or PR and the initiation of consolidation treatment was allowed. Patients who completed consolidation treatment started maintenance treatment of cytarabine at 10 mg/m\^2 sc bid on days 1-7 of a 28-day cycle. Patients started maintenance treatment within 42 days after platelet count recovery. Maintenance treatment continued for 2 years or until unacceptable toxicity or disease progression.

Drug: Low-dose cytarabine alone

Interventions

Arsenic trioxide DRUG

Arsenic trioxide will be administered intravenously (iv) at a dose of 0.25 mg/kg.

Low-dose cytarabine plus arsenic trioxide

Low-dose cytarabine alone DRUG

Cytarabine will be administered at a dose of 10 mg/m\^2 subcutaneously (sc) twice a day (bid).

Low-dose cytarabine alone; Low-dose cytarabine plus arsenic trioxide

Eligibility Criteria

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

You may qualify if:

• The patient has confirmed acute myeloid leukemia (AML).
• The patient is unwilling or unable to tolerate conventional induction chemotherapy.
• The patient has no comorbid conditions that would limit life expectancy to less than 3 months.

You may not qualify if:

• \- The patient has had previous cytotoxic chemotherapy for acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS).
• Previous treatment with low-dose cytarabine is not permitted.
• The patient has a QT interval outside of the protocol-specified range.
• The patient has laboratory values outside of protocol-specified ranges.
• The patient is concurrently treated with cytotoxic therapy, radiation, or investigational agents.
• The patient has uncontrolled, severe cardiovascular or pulmonary disease or other uncontrolled medical condition.
• The patient has known central nervous system involvement with AML.

Sponsors & Collaborators

• Cephalon: lead

Study Sites (12)

USC / Norris Cancer Hospital

Los Angeles, California, 90033, United States

Location

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

University of Illinois

Chicago, Illinois, 60612, United States

Location

Indiana Oncology Hematology Consultants

Indianapolis, Indiana, 46202, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

St. Vincent's Comprehensive Cancer Center

New York, New York, 10011, United States

Location

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Brody School of Medicine

Greenville, North Carolina, 27834, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

UT Health Science Center

San Antonio, Texas, 78229, United States

Location

Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Arsenic Trioxide; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

In September 2009, the sponsor decided to stop the study due to difficulty in enrollment. The study was stopped prior to the first planned interim analysis. Most of the analysis planned in the protocol was not performed.

Results Point of Contact

• Title: Sponsor's Medical Expert, Clinical Research
• Organization: Cephalon, Inc.

1-800-896-5855

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2007
• First Posted: August 8, 2007
• Study Start: October 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: December 1, 2009
• Last Updated: August 1, 2012
• Results First Posted: March 29, 2011

Record last verified: 2012-07

Locations

CA (1); US (11)